Title of Invention

DIBENZYLAMINE COMPOUNDS, A PHARMACEUTICAL COMPOSITION COMPRISING THE SAME

Abstract A dibenzylamine compound represented by the general formula (1): (1) (wherein R<sup>1</sup> and R<sup>2</sup> each is optionally halogenated C<sub>1</sub>-<sub>6</sub> alkyl, etc.; R<sup>3</sup>, R<sup>4</sup>, and R<sup>5</sup> each is hydrogen, halogeno, etc., provided that R<sup>3</sup> and R<sup>4</sup> may form an optionally substituted homocycle or heterocycle in cooperation with the carbon atoms bonded thereto; A is -N(R<sup>7</sup>)(R<sup>8</sup>), etc.; ring B is aryl or a heterocyclic residue; R<sup>6</sup> is hydrogen, halogeno, nitro, C<sub>1</sub>-<sub>6</sub> alkyl, etc.; and n is an integer of 1 to 3); a prodrug of the compound; or a pharmaceutically acceptable salt of either. They have selective and potent CETP inhibitory activity and are hence usable as, e.g., a therapeutic or preventive drug for hyperlipemia, arteriosclerosis, etc.
Full Text DIBENZYLAMINE CXDMPOUNDS AND PHARMACBDTICAL USE THEREOF
Technical Field
The present, invention relates to a novel CETP activity Inhibitor, particularly a therapeutic agent or a prophylactic agent of arteriosclerosis or hyperlipidemia.
Background Art:
Regarding the relationship between arteriosclerotic iiseases and serum lipoprotein, it has been considered for some time that a certain relationship exists frcan the results )f many epidemiological researches. For exan^le, Badiraon et al. [J. Clin. Invest., 85, 1234-1241 (1990)) reported that .ntravenous injection of fractions containing HDL (high iensity lipoprotein) and VHDL (very high density lipoprotein) :o cholesterol-loaded rabbits resulted in the observation of lot only prevention of progression of arteriosclerotic lesion )ut also regression thereof, and HDL and VHDL are considered :o have an anti-arteriosclerotic action in the relationship )etween arteriosclerotic diseases and serum lipoprotein.
In recent years, the presence of a protein that transfers ipid between blood lipoproteins, or CETP (cholesteryl ester ransfer protein), has been clarified. The presence of CETP as first pointed out in 1965 by Nichols i Smith (J. Lipid :es., 6, 206, 1965), and thereafter its cDtiA was cloned in 987 by Drayna et al. The molecular weight thereof is 74,000 a as glycoprotein and about 58,000 Da when sugar chain is ompletely cleaved. Its cDNA consists of 1656 residues and ncodes 476 amino acids following 17 signal peptides. Since bout 44% thereof consists of hydrophobic amino acids, it has xtremely high hydrophobicity and is easily inactivated by xidation. In addition, it has been confirmed that CETP is reduced in the organs such as liver, spleen, adrenal gland, dipose tissue, small intestine, kidney, skeletal muscle,
^"
r

heart muscle and the like, and produced in cells of the cell types of human monocyte-derived macrophage, B lymphocyte, fat cell, small intestinal epithelial cell, CaCo2 cell, hepatocyte (exemplified by human liver cancer cell-derived cell line, HepG2 cells) and the like. Besides the above-mentioned tissues it is present in cerebrospinal fluid and semen, and its presence has been confirmed in culture media of hviman neuroblastoma and neuroglioma cells, choroid plexus of sheep and the like.
It has been also clarified that CETP is involved in the metabolism of any lipoprotein in living organisms, and has a major role in the reverse cholesterol transfer system. Namely, CETP has drawn attention as a mechanism for preventing accumulation of cholesterol in peripheral cells and preventing arteriosclerosis. In fact, with regard to HDL having an important role in this reverse cholesterol transfer system, a number of epidemiological researches have shown that a decrease in CE (cholesteryl ester) of HDL in blood is one of the risk factors of coronary artery diseases. It has been also clarified that the CETP activity varies depending on the mimal species, wherein arteriosclerosis due to cholesterol-Loading is hardly induced in animals with lower activity, and Ln reverse, easily induced in animals with higher activity, md that hyper-HDL-emia and hypo-LDL (low density Lipoprotein)-emia are induced in the case of CETP deficiency, ius rendering the development of arteriosclerosis difficult, ?hich in turn led to the recognition of the significance of )lood HDL, as well as significance of CETP that mediates iransfer of CE in HDL into blood LDL.
Free cholesterol (FC) synthesized in and secreted from lie liver is taken up by very low density lipoprotein (VLDL). "hen, due to the action of lipoprotein lipase (LPL) and lepatic triglyceride lipase (HTGL), VLDL is metabolized in

blood into LDL via intermediate density lipoprorein (IDL). LDL is taken up by peripheral cells via an LDL receptor and FC is supplied to the cells. Conversely from such flow from t±ie liver to the peripheral cells, there exists a flow of cholesterol from peripheral cells toward the liver, which is called a reverse cholesterol transfer system. In other words, FC accumulated in the peripheral tissues is drawn by HDL, further esterified on HDL by the action of LCAT (lecithin-cholesterol acyltransferase) to form CE, and transferred to the hydrophobic core part of HDL, whereby HDL matures into spheric HDL particles. CE in HDL is transferred by CETP present in blood to apoB-containing lipoproteins such as VLDL, IDL, LDL and the like, and in return, TG is transferred to HDL at a molar ratio of 1:1. CE transferred to apoB-containing lipoprotein is taken up by the liver via LDL receptor in the liver, thereby indirectly transferring cholesterol to the liver. Moreover, there is a mechanism in which HDL takes up apoprotein E secreted from macrophage and the like to become apoprotein E-containing HDL rich in CE, and then is directly taken up by the liver via LDL receptor or remnant receptor. There also exists a path in which HDL particles are not taken ap by the liver and only CE in HDL is selectively taken up by lepatocytes. Furthermore, another path exists in which HDL particles are taken up by hepatocytes via what is called an iDL receptor in the liver.
Namely, in the state of enhanced CETP activity, since CE transfer from HDL increases, CE in HDL decreases, and CE in /LDL, IDL and LDL increases. When take up of IDL and LDL by ihe liver increases, down-regulation is imposed on the LDL receptor, and LDL in blood increases. In contrast, in the CETP ieficient state, HDL draws cholesterol from peripheral cells tfith the aid of LCAT, gradually increases its size and icquires apo E. Then, apo E-rich HDL is taken up by the liver

via LDL receptor in the liver and catabolized. However, since tiiis mechanism"does not function sufficiently in human, large HDL dwells in the blood. Consequently, cholesterol pool in the liver becomes smaller and up-regulation is imposed on the LDL receptor, thereby decreasing LDL. Accordingly, selective inhibition of CETP can lower IDL, VLDL and LDL that promote arteriosclerosis and increase HDL that acts suppressively thereon, and produces expectation for the provision of an unprecedented prophylactic or therapeutic agent for arteriosclerosis or hyperlipidemia.
While many attempts have been made in recent years to develop a drug that inhibits such activity of CETP, a compound having a satisfactory activity has not been developed yet.
Meanwhile, many reports have been found recently on the compounds aiming at inhibiting such activity of CETP. For example. Biochemical and Biophysical Research Communications 223, 42-47 (1996) discloses dithiodipyridine derivatives, substituted dithiodibenzene derivatives and the like as :;ompounds that inactivate CETP by modifying cysteine residue, iowever, this reference does not contain any description of the compound of the present invention, not to mention a iescription suggestive thereof.
In addition, WO95/06626 discloses Wiedendiol-A and *iedendiol-B as CETP activity inhibitors. However, this publication does not contain any description suggesting the ;ompound of the present invention.
Moreover, JP-B-45-11132, JP-B-45-2892, JP-B-45-2891, JP-J-45-2731 and JP-B-45-2730 disclose mercaptoanilides substituted by higher fatty acid such as o-
-sostearoylaminothiophenol and the like, as a compound having m action to prevent arteriosclerosis. However, these )\iblications only mention the presence of an effect to prevent irteriosclerosis and lack description of Exp>erimental Example

that support the effect, much less a description of inhibition of CETP activity. Moreover, no description is found that suggests the compound of the present invention.
JP-T-2001-512416 (WO98/04528) discloses a biaryl compound that inhibits CETP. However, this publication has no description that suggests the compound of the present invention.
WOOO/17164, WOOO/17166 and WOOl/40190 disclose 4-carboxyamino-2-substituted-l,2,3,4-tetrahydroquinoline as a CETP inhibitor. However, these publications contain no description that suggests the compound of the present invention.
On the other hand, various compounds having a structure like the compound of the present invention have been reported. For example, JP-A-2001-106666 and WOOl/10825 disclose carbamate derivatives characterized in that phenyl group has an oxime ether group. However, the compounds of these publications are compounds useful as antimicrobial agents for agriculture or gardening, and they lack a disclosure of usefulness as a CETP activity inhibitor, or even a description suggestive thereof.
WOOO/69810 discloses compounds such as 3-(4-{[N-[3-(2,6-dichlorophenyl)acryloyl]-N-(4-tert-
butylbenzyl) ainino]methyl}benzoylamino)propionic acid and the like. However, the compound of this publication is useful as i glucagon antagonist, and this publication lacks a disclosure of usefulness as a CETP activity inhibitor, or even a description suggestive thereof.
WO99/67204 discloses compounds such as l-[N-(4-chlorobenzyl)-N-(N,N-dimethylcarbamoyl) amincanethyl]-4-guanidinomethylbenzene and the like. However, the compound of this publication is useful as an analgesic, and this publication lacks a disclosure of usefulness as a CETP

activity inhibitor, or even a description suggestive thereof.
W099/44987 and US6,218,426 disclose compounds such as N-(4-tert-butylbenzyl)-N-[4-(guanidinomethyl)benzyljbenzamide and the like useful as a gonadotropin-releasing hormone antagonist/agonist. However, this publication lacks a disclosure of usefulness as a CETP activity inhibitor, or even a description suggestive thereof.
US5,834,514 and JP-T-9-512556 (W095/29672) disclose that haloroethylamide compounds such as N-benzyl-N-(2,4-dichlorobenzyl) chloroacetaitiide and the like are useful as IL-I3 protease activity inhibitors. However, these publications lack a disclosure of usefulness as a CETP activity inhibitor, or even a description suggestive thereof.
W097/24328 discloses 2-amino-heterocyclic compounds such as N,N-bis(2,4-dimethoxybenzyl)-N"-(4-methoxyphenyl)urea and the like. However, the compound of this publication is useful as a leukotriene synthesis inhibitor and this publication lacks a disclosure of usefulness as a CETP activity inhibitor, or even a description suggestive thereof.
WO96/10559 discloses urea derivatives such as 1-benzyl-l-[3-(pyrazol-3-yl)benzyl]-3-(2,4,6-trimethylphenyl)urea and the like. However, the compound of this publication is useful as aji acyl-CoA: cholesterol acyltransf erase inhibitor and this publication lacks a disclosure of usefulness as a CETP activity inhibitor, or even a description suggestive thereof. "
US4,623,662 discloses that urea compounds such as 1-benzyl-1-(2,4-dichlorobenzyl)-3-(2,4-dimethylphenyl)urea and the like are useful as acyl-CoA:cholesterol acyltransferase inhibitors. However, this publication lacks a disclosure of asefulness as a CETP activity inhibitor, or even a description suggestive thereof.
US4,473,579 discloses urea compounds such as 1,1-iibenzyl-3-(2,4-dimethylphenyl)-3-phenylurea and the like.

However, t±ie compound of this publication is useful as an acyl-CoA: cholesterol acyltransferase irJiibitor and "Lhis publication lacks a disclosure of usefulness as a CETP activity inhibitor, or even a description suggestive thereof.
US4,122,255, US4,064,125, US4,151,354 and US4,127,606 disclose compounds such as N-[[2-[3-(dimethylamino)propoxy]phenyl]methyl]-3-phenyl-N-(phenylmethyl)-2-propenamide and the like. However, the compounds of these publications are useful as antiinflammatory agents and they lack a disclosure of usefulness as a CETP activity inhibitor, or even a description suggestive thereof.
WO99/18066 discloses amide carboxylic acid compounds sue! as ethyl 2-butyl-3-[4-[2-[N-benzyl-(4-pyridin-2-^1)aminoJethoxy]phenyl]propionate and the like having useful Lipid-lowering action and the like. However, this publication Lacks a disclosure of usefulness as a CETP activity inhibitor, >r even a description suggestive thereof. Moreover, this >ublication lacks a disclosure of a structure such as the zompound of the present invention, or even a description suggestive thereof.
In contrast, WOOO/18724 discloses a compound having a itructure similar to that of the present invention and a CETP .nhibitory activity. To be specific, the following formula is Lisclosed.


When R2 and R3 form a hetero ring or cycloalkenyl in combination, the compound is structurally similar to the present invention. However, this invention lacks a concrete disclosure (Example) of ring B as shown in the present invention. In addition, this invention is distinct from the present invention in that the invention always has Ri (haloalkyl, haloalkenyl, haloalkoxyalkyl or haloalkenyloxyalkyl).
In other words, this invention does not disclose a concrete structure as the compound of the present invention, not to mention a description suggestive thereof.
Disclosure of the Inventicm
The present invention aim?^ at providing a novel compouni that selectively inhibits the activity of GET?. The present invention also aims at providing a compound useful as a prophylactic or therapeutic agent of arteriosclerosis or hyperlipidemia, which increases HDL cholesterol and simultaneously decreases LDL cholesterol and triglyceride by selectively inhibiting the activity of CETP, and which is free of a CYP inhibitory effect.
The present inventors have conducted intensive studies in

an attempt to achieve the above-mentioned objects and found that the compounds shown in the following [1] ~o [13] have an effect to selectively inhibit the activity of CETP (hereinafter to be referred to as a CETP inhibitory effect), and are useful pharmaceutical agents, particularly, prophylactic or therapeutic agents of arteriosclerosis or hyperlipidemia. Moreover, they have found that a structure such as the formula (1) provides a potent CETP inhibitory effect, which resulted in the completion of the present invention. More particularly, the following [1] to [76] are provided. [1] A dibenzylamine compound represented by the formula (1)

wherein
R^ and R^
are the same or different and each is a halogen atoi a nitro group, a cyano group or a Ci-4 alkyl group optionally substituted by halogen atoms;
R^ R^ and R^
are the same or different and each is a hydrogen at( a halogen atom, a Ci_6 alkyl group optionally substituted by halogen atoms, a Ci-g alkylthio group optionally substituted by halogen atcxas or a Ci-e alkoxy group optionally substituted by halogen atoms, or R^ and R* or R* and R^ may form, together with carbon atoms bonded thereto, a hornocyclic ring

optionally having substituent (s) or a hererocyclic ring optionally having substiruent(s); is -N(R") (R^) (wherein R" and R^ are rhe same or different and each is a hydrogen atom, a Ci-s alkyl group (wherein Ci-e alkyl group is optionally substituted by phenyl group or
- (CHz)a-COOR^ (wherein R^ is a hydrogen atcan or a Ci-e alkyl group and m is 0 or an integer of 1 to 5)) or a C4-10 cycloalkylalkyl group (wherein C4-10 cycloalkylalkyl group is optionally substituted by 1 to 3 substituents from halogen atom, nitro group, amino group, hydroxyl group, cyano group, acyl group, Ci_6 alkoxy group, Ci-e alkyl group (wherein Ci-g alkyl group is optionally substituted by hydroxyl group, Ci. alkoxy group or phosphono group), - (CH2) q-CON (R^°) (R^^) (wherein R^° and R^"" are the same or different and ead is hydrogen atom or Ci-e alkyl group and q is 0 or an integer of 1 to 5) or - (CH2) r-COOR" (wherein R" is hydrogen atom or Ci-e alkyl group and r is 0 or an integer of 1 to 5))), -C(R^^) (R") (R") (wherein R^\ B} and R^^ are the same or different and each is a hydrogen atom, a Ci_6 alkyl group (wherein Ci_6 alkyl group is optionally substituted by phenyl group or -COOR" (wherein R^ is as defined above) ) or a C4-10 cycloaUcylalkyl group (wherein C4-10 cycloalkylalkyl group is optionally substituted by 1 to 3 substituent from halogen atom, nitro group, amino group, hydroxyl group, cyano group, acyl group, Ci-e alkoxy group, Ci_t alkyl group (wherein Ci-e alkyl group is optionally substituted by hydroxyl group, Ci-t alkoxy group or phosphono group), - (CH2) q-CON (R") (R^) (wherein R^°, R^ and q are as defined above) or - (CHz) r-COOR*° (wherein R^° and r are as defined above))) or -0-C(R") (R") (R")

(wherein R""", R"^ and R""""^ are as defined above) ;
ring B is an aryl group or a heterocyclic residue;
R^ is a hydrogen atom, a halogen arom, a nirro group, an amino group, a hydroxyl group, a cyano group, an acyl group, a Ci-g alkoxy group, a C2~£ alkenyl group or a Ci-e alkyl group (wherein Ci_6 alkyl group is optionally substituted by hydroxyl group or -COOR^* (wherein R^* is a hydrogen atom or a Ci-e alkyl group) ) ; and
n is an integer of 1 to 3
or a prodrug thereof or a pharmaceutically acceptable salt
thereof.
[2] The dibenzylamine compound of the above-mentioned [1]
wherein
R^ R^ and R^
are the same or different and each is a hydrogen atom, a halogen atom, a Ci-e alkyl group optionally substituted by halogen atoms or a Ci-e alkoxy group optionally substituted by halogen atoms, or R^ and R^ or R* and R^ may form, together with carbon atoms bonded thereto, a hpmocyclic ring optionally having substituent(s) or a heterocyclic ring optionally having substituent(s);
R" and R^
are the same or different and each is a hydrogen atom, a Ci-e alkyl group (wherexn C_6 alkyl group is optionally substituted by phenyl group or -COOR^ (wherein R^ is a hydrogen atom or a Ci-e alkyl group) ) or a Cfl-io cycloalkylalkyl group (wherein C4-10 cycloalkylalkyl group is optionally substituted by 1 to 3 substituents from halogen atom, nitro group, amino group, hydroxyl group, cyano group, acyl group, Ci-6 alkoxy group, Ci-e alkyl group or -COOR"° (wherein R^" is a hydrogen atom or a Ci-g alkyl group) ) ;

R-\ R^^ and R^^
are the same or different and each is a hydrogen atom, a Ci-e alkyl group (wherein d.-g alkyl group is optionally substituted by phenyl group or -COOR^ (wherein R^ is as defined above) ) or a C4-10 cycloalkylalkyl group (wherein C^-IQ cycloalkylalkyl group is optionally substituted by 1 to 3 substituents from halogen atom, nitro group, amino group, hydroxyl group, cyano group, acyl group, Ci-s alkoxy group, Ci_6 alkyl group or -COOR^° (wherein R^° is as defined above));
is a hydrogen atom, a halogen atom, a nitro group, an amino group, a hydroxyl group, a cyano group, an acyl group, a Ci-e alkoxy group or a Cis alkyl group (wherein Ci-e alkyl group is optionally substituted by hydroxyl group or -COOR^* (wherein R^* is a hydrogen atom or a Ci-e alkyl group) ) ,
or a prodrug thereof or a pharmaceutically acceptable salt
thereof.
[3] The dibenzylamine compound of the above-mentioned [1] or
[2] , wherein R^ is a Ci-e alkyl group substituted by halogen
atoms, or a prodrug thereof or a pharmaceutically acceptable
salt thereof.
[4] The dibenzylamine compound of the above-mentioned [3],
wherein R^ is a trifluoromethyl group, or a prodrug thereof or
a pharmaceutically acceptable salt thereof.
[5] The dibenzylamine compound of the above-mentioned [1], [3]
or [4], wherein ring B and (R^)ii are each


wherein R^°, R^^ and R" are the same or different and each is a hydrogen atom, a halogen atom, a nitro group, an amino group, a hydroxy! group, a cyano group, an acyl group, a Ci-g alkoxy /^ group, a C2-6 alkenyl group or a Ci-e alkyl group (wherein Ci_6 alkyl group is optionally substituted by hydroxyl group or -COOR^* (wherein R^^ is as defined above)) or a prodrug thereof or a pharmaceutically acceptable salt thereof.

[6] The dibenzylamine compound of the a±)ove-mentioned [5] , wherein ring B and (R*)n are each

wherein R^°, R^^ and R" are as defined above or a prodrug 1 thereof or a pharmaceutically acceptable salt thereof.
[7] The dibenzylamine compound of the above-mentioned [6], wherein ring B and (R^)n are each

wherein R^"" and R^^ are as defined above or a prodrug thereof or
a pharmaceutically acceptable salt thereof.
[8] The dibenzylamine compound of any of the above-mentioned
[1] and [3] to [7], wherein A is -N(R") (R^) (wherein R" and R^ are as defined in the above-mentioned [1]) or a prodrug thereof or a pharmaceutically acceptable salt thereof.
[9] The dibenzylamine compound of the above-mentioned [8], wherein R" is a Ci-e alkyl group or a prodrug thereof or a pharmaceutically acceptable salt thereof.
[10] The dibenzylamine compound of the above-mentioned [9], wherein R^ is a Ci-e alkyl group or a prodrug thereof or a

pharmaceutically acceptable salt thereof.
[11] The dibenzylamine compound of the above-mentioned [1], which is selected from the group consisting of N-[3-(N"-cyclopentylmethyl-N"-ethylamino)-5,6,7,8-tetrahydronaphthalen-2-ylmethyl]-N- [3,5-
bis(trifluoromethyl)benzyl]-(2-methyl-2H-tetrazol-5-yl)amine, 3-{[N-[3-(N"-cyclopentylmethyl-N"-ethylamino)-5,6,7,8-tetrahydronaphthalen-2-ylmethyl]-N-(2-methyl-2H-tetra2ol-5-yl)amino]methyl}-5-trifluoromethyIbenzonitrile, N-[3,5-bis (trifluoromethyl)benzyl]-N-[6- (N"-cyclop>entylmethyl-^}"-ethylamino) indan-5-ylmethyl] - (2-methyl-2H-tetrzol-5-Y1)amine,
^- [3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-^"-ethylamino)indan-5-ylmethyl]-(2-methyl-2H-tetrazol-5-1^1) amine hydrochloride,
^-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-N-(2H-tetrazol-5-yl)-[3,5-bis(trifluoromethyl)benzyl]amine, I-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-N-;3,5-bis(trifluoromethyl)benzyl]-(pyrimidin-2-yl)amine
lydrochloride,
I- [6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-N-
3,5-bis(trifluoromethyl)benzyl]-(5-methyl-lH-pyrazol-3-
1)amine,
-{N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(5-raethyl-
1,2,4]oxadiazol-3-yl)amino]methyl}indan-5-yl)-N-
thylamino}pentanoic acid hydrochloride,
ethyl trans-4-{ [N-(2-{ [N"-[3 , 5-bis (trifluorcanethyl) benzyl]-
"-(2-methyl-2H-tetrazol-5-yl)amino]methyl)-4-
rifluoromethoxyphenyl)-N-
thylamino]methyl}cyclohexanecarboxylate,
-{[N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-
lmethyl]-N- (2-methyl-2H-tetrazol-5-yl) amino]metliyl}-5-
rifluoromethyIbenzonitrile,

N- [3 , 5-bis (trif luoromeiihyl) benzyl] -Ki- [6- (N"-cyclopenrylmet±iyl-N "-ethylamino) indan-5-ylmetiiyl] - (2-et±iyl-2H-i:errazol-5-yl)amine,
N-[3,5-bis(trifluoromeUiyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-yImethyl]-(1-methy1-lH-[1,2,4]triazol-3-yl) aitvine,
3-({N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-N-phenylaminoImethyl)-5-trifluorcxnethylbenzonitrile, 3-{[N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-N- (4,5-dimethyl-thiazol-2-yl) aminoJmethyD-S-trif luoromethylbenzonitrile ,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-y Imethyl]-(thiazol-2-yl)amine hydrochloride,
3-({N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-N-{thiazol-2-Yl)amino}methyl)-5-trifluororaethylbenzonitrile hydrochloride,
^-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-*J"-ethylamino) indan-5-yImethyl] - (oxazol-2-yl) amine lydrochloride,
^-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-J"-ethylamino) indan-5-ylmethyl] - (5-methylth.iazol-2-yl) amine lydrochloride,
I-[3,5-bis (trifluoromethyl)benzyl]-N-[6-{N"-cyclop«ntylmethyl-I"-ethylamino) jjidan-S-yImethyl] - (4-methyltliiazol-2-yl) amine lydrochloride,
I- [3, 5-bis (trifluoromethyl) benzyl]-N- [6- (N"-cyclop>entylmethyl-["-ethylamino)indan-5-ylmethyl]-(4,5-dimethylthiazol-2-l)amine hydrochloride,
-{[N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-S-Imethyl]-N-(5-methylthiazol-2-yl)amino]methyl}-5-rifluoromethyIbenzonitrile hydrochloride, -{[N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-

ylmet±iyl]-N- {4-me"Lhyl"i±Liazol-2-yl) aminojmerhyl}-5-
trifluoromethylbenzonitrile hydrochloride,
N- [3 , 5-bis (trifluorometiiyl) benzyl] -N- [6- {N"-cyclopenrylmerhyl-
N"-ethylamino) indan-5-ylmethyl]- (4-met±iyloxazol-2-yl) amine
hydrochloride,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-
N"-ethylamino)indan-5-ylmethyl]-(3-methylisot±Liazol-5-yl)amine
hydrochloride,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-
N"-ethylamino)indan-5-ylmethyl]-(5-methylisoxazol-3-yl)amine
hydrochloride,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-
N"-ethylamino)indan-5-ylmethyl]-(3-methylisoxazol-5-yl)amine
hydrochloride,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-
N"-ethylamino)indan-5-ylmethyl]-(l-methyl-lH-pyrazol-3-
yl)amine hydrochloride,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-
N"-ethylamino)indan-5-ylmethyl]-(l-methyl-lH-pyrazol-4-
yl) amine hydrochloride,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-
N"-ethylamino)indan-5-ylmethyl]-(5-methyl-[1,3,4]thiadiazol-2-
yl)amine hydrochloride,
N-[3 , 5-bis (trifluoromethyl) benzyl] -N- [6- (N"-cyclop>er.tylmethyl-
N"-ethylamino)indan-5-ylmethyl]-(5-methyl-[1,3,4]oxad i azol-2-
yl)amine hydrochloride,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[5-(N"-cyclopentylmethyl-
N"-ethylamino)indan-5-ylmethyl]-pyridin-3-ylamine
hydrochloride,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-
N"-ethylamino)indan-5-ylmethyl]-pyridin-2-ylamine
hydrochloride,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[2-(N"-cyclopentylmethyl-

N "-ethylamino) -5-trif luoromethylbenzyl] - (2-n:iethyl-2H-retrazol-
5-yl)amine hydrochloride,
3- { [N- [2- {N"-cyclopentyimet:hyl-N"-et±iylamino) -5-
trif luoroinet±iylbenzyl] -N- (2-methyl-2H-tetrazol-5-
yl)amino]methyl}-5-trifluoromethylbenzonitrile hydrochloride,
methyl 5-IN-(6-{ [N"-[3,5-bis (trifluoromethyDbenzylJ-N"-(2-
met±iyl-2H-tetrazol-5-yl) amino]met±iyl}indan-5-yl) -N-
ethylamino]pentanoate hydrochloride,
methyl 5-[N-(6-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-(2-
methyl-2H-tetrazol-5-yl) amino]methyl }indan-5-ylinethyl) -N-
ethylamino]pentanoate hydrochloride,
methyl 5-[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(1-
methyl-lH-pyrazol-3-yl)amino]methyl}indan-5-yl)-N-
ethylamino]pentanoate hydrochloride,
5-[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-
tetrazol-5-yl) amino]methyl} indan-5-yl) -N-ethylainino]pentanoic
acid hydrochloride,
5-[N-(6-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-(2-methyl-
2H-tetrazol-5-yl)amino]methyl}indan-5-yl)-N-
ethylaminojpentanoic acid hydrochloride,
5-[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(3-
methylisoxazol-5-yl)amino]methyl}indan-5-yl)-N-
ethylamino]pentanoic acid hydrochloride,
5-[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(l-nethyl-lH-
pyrazol-3-yl)am±no]methyl}indan-5-yl)-N-ethylami nojpentanoic
acid hydrochloride,
methyl trans-4-{[N-(3-{[N"-[3,5-bis(trifluoromethyl)benzyl]-
N"-(l-methyl-lH-pyrazol-3-yl)amino]methyl)-5,6,7,8-
tetrahydronaphthalen-2-yl)-N-
ethylamino]methyl}cyclohexanecarboxylate hydrochloride,
Tiethyl trans-4-{ [N-(3-{ [N"-(3-cyano-5-trif luoromethylbenzyl)-
!^" - (l-methyl-lH-pyrazol-3-yl) amino]methyl}-5,6,7 ,8-
tetrahydronaphthalen-2-yl)-N-

etjiylamino] raeriiyl} cyclohexanecarboxylate hydrochloride, 1:rans-4-{ [N-(3-{ [N"-C3,5-bis (trifluoromethyl) benzyl]-N"- (1-methyl-lH-pyrazol-3-yl)amino]methyl}-5,6,7,8-tet:rahydronaph"thalen-2-yl)-N-
et±iylaJiiino]met±iyl}cyclohexanecarboxylic acid hydrochloride, trans-4-{ [N-(3-{ [N"-(3-cyano-5--trifluororae1:hylbenzyl)-N"-(1-met±iyl-lH-pyrazol-3-yl) amino]methyl} -5 , 6 ,7 , 8-tetrahydronaphthalen-2-yl)-N-
ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride, N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethyiamino)indan-5-ylmethyl]-{5-methyl-[1,2,4]oxadiazol-3-yl) amine hydrochloride,
methyl trans-4-{[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(l-methyl-lH-pyrazol-3-yl)amino]methyl}indan-5-yl)-N-ethylamino]methyl}cyclohexanecarboxylate hydrochloride, trans-4-{[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(1-methyl-lH-pyrazol-3-yl)amino]methyl}indan-5-yl)-N-ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride, methyl trans-4-{[N-(6-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"- (l-methyl-lH-pyrazol-3-yl)amino]methyl}indan-5-yl)-N-ethylamino]methyl}cyclohexanecarboxylate,
trans-4-{[N-(6-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-(1-tnethyl-lH-pyrazol-3-yl) amino]methyl}indan-5-yl) -N-ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride, traiis-4-{ [N-(6-{ [N"-[3,5-bis (trifluoromethyl) benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}indan-5-yl)-N-ethylamino]raethyl}cyclohexanecarboxylic acid hydrochloride, trans-4-{[N-(6-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-(2-[nethyl-2H-tetrazol-5-yl) amino]methyl}indan-5-yl) -N-ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride, trans-4-{[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzylj-N"-(3-Bethylisoxazol-5-yl)amino]methyl}indan-5-yl)-N-ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride.

trans-4-{[N-(6-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-(3-
metiylisoxazol-5-yl) amino]met±iyl}indan-5-yl) -N-
ethylaniino]methyl}cyclohexanecarboxylic acid hydrochloride,
methyl 5-[N-{6-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-(1-
methyl-lH-pyrazol-3-yl)amino]methyl}indan-5-yl)-N-
ethylamino]pentanoate hydrochloride,
5-[N-(6-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-(3-raethyl-
isoxazol-5-yl)amino]methyl}indan-5-yl)-N-ethylamino]pentanoic
acid hydrochloride,
5-[N-(6-([N"-(3-cyano-5-trifluoromethylbenzyl)-N"-(1-methyl-
lH-pyra2ol-3-yl)amino]methyl}indan-5-yl)-N-
ethylamino]pentanoic acid hydrochloride,
5-[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(1-methyl-lH-
[1,2,4]triazol-3-yl)amino]methyl}indan-5-yl)-N-
ethylaraino]pentanoic acid hydrochloride,
trans-4-{[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(1-
nethyl-lH-[1,2,4]triazol-3-yl)amino]methyl}indan-5-yl)-N-
2thylamino]raethyl}cyclohexanecarboxylic acid hydrochloride,
trans-4-{[N-(6-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-(1-
nethy1-lH-[1,2,4]triazol-3-yl)amino]methyl}indan-5-yl)-N-
Jthylamino]methyl}cyclohexanecarboxylic acid,
I-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-
r-ethylamino)indan-5-ylmethyl]-(3-methyl-[1,2,4]thiadiazol-5-
^1) amine,
i-[N-(6-{[N"-(S-cyano-S-trifluoromethylbenzyl)-N"-(1-methyl-
H-[1,2,4]triazol-3-y1)amino]methyl}indan-5-yl)-N-
ithylamino]pentanoic acid hydrochloride,
lethyl 5-[N-(3-{ [N"-[3,5-bis (trifluoromethyl) benzyl]-N"-(1-
iethyl-lH-pyrazol-3-yl)amino]methyl}-5,6,7,8-
etrahydronapht±ialen-2-yl)-N-ethylamino]pentanoate
ydrochloride,
erhyl 5-[N-(3-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-(1-
ethyl-lH-pyrazol-3-yl)amino]methyl}-5,6,7,8-

tet.rahycironaphtialen-2-yl) -N-ethylaminojpentanoate
hydrochloride,
5-[N-(3-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(1-methyl-lH-
pyrazol-3-yl)amino]methyl}-5,6,7,8-tetrahydronaphthalen-2-yl)-
N-ethylamino]p>entanoic acid hydrochloride,
5-[N-(3-{[N"-(3-cyano-5-trifluororaethylbenzyl)-N"-(1-methyl-
lH-pyrazol-3-yl)amino]methyl}-5,6,7,8-tetrahydronaphthalen-2-
yl)-N-ei±iylamino]pentanoic acid hydrochloride,
trans-4-{[N-(3-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
methyl-2H-tetrazol-5-yl)amino]methyl}-5,6,7,8-
tetrahytlronaphthalen-2-yl) -N-
ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride,
trans-4-{[N-(3-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-(2-
methyl-2H-tetrazol-5-yl)amino]methyl}-5,6,7,8-
tetrahydronaphthalen-2-yl)-N-
ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride,
trans-4-{[N-(3-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(1-
nethyl-lH-[1,2,4]triazol-3-yl)amino]methyl}-5,6,7,8-
tetrahydronaphthalen-2-yl)-N-
ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride,
trans-4-{[N-(3-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-(1-
nethyl-lH-[1,2,4]triazol-3-yl)amino]methyl}-5,6,7,8-
tetrahydronaphthalen-2-yl)-N-
sthylamino]methyl}cyclohexanecarboxylic acid,
traiis-4-{ [N-(3-{ [N"-[3,5-bis (trifluoromethyl) benzyl]-N"-(3-
nethylisoxazol-5-yl)amino]methyl}-5,6,7,8-
tetrahydronaphthalen-2-yl)-N-
5thylamino]methyl}cyclohexanecarboxylic acid hydrochloride,
irans-4-{[N-(3-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-(3-
aethylisoxazol-5-yl)amino]methyl}-5,6,7,8-
:etraLhydronaphthalen-2-yl) -N-
5T:hylamino]merhyl} cyclohexanecarboxylic acid hydrochloride,
?-(5-{N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-

cyclopentylmethyl-N"-etliylainino) indan-5-yImetJiyl]amino}tetrazol-2-yl) etJianol hydrochloride, methyl 5-[N-(3-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(1-raethyl-lH-[1,2,4]triazol-3-yl)amino]methyl}-5,6,7,8-tetrahydronaphthalen-2-yl)-N-ethylamino]pentanoate hydrochloride,
methyl 5-[N-(3-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-(1-methyl-lH-[1,2,4]triazol-3-yl)amino]methyl}-5,6,7,8-tetrahydronaphthalen-2-yl)-N-ethylamino]pentanoate hydrochloride,
5-[N-(3-{IN"-[3,5-bis(trifluoromethyl)benzyl]-N"-(1-methyl-lH-[1,2,4]triazol-3-yl)amino]methyl}-5,6,7,8-tetrahydronaphthalen-2-yl)-N-ethylamino]pentanoic acid hydrochloride,
5-[N-(3-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-(1-methyl-IH-[1,2,4]triazol-3-yl)amino]methyl}-5,6,7,8-tetrahydronaphthalen-2-yl)-N-ethylamino]pentanoic acid hydrochloride,
5-[N-(3-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(3-methylisoxazol-5-yl)amino]methyl}-5,6,7,8-tetrahydronaphthalen-2-yl)-N-ethylamino]pentanoic acid hydrochloride,
5-[N-(3-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-(3-methylisoxazol-5-yl)amino]methyl}-5,6,7,8-tetrahydronaphthail en-2-yl) -N-ethylamino]pentanoic acid hydrochloride,
5-[N-(3-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl) amino]methyl}-5, 6 ,7 , 8-tet:rahydronaphthalen-2-/l)-N-ethylamino]pentanoic acid hydrochloride, 5-[N-(3-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-5,6,7,8-tetrahydronaphthalen-2-/l)-N-ethylamino]pentanoic acid hydrochloride, t:rans-4-{ [N- (6-{ [N"-[3,5-bis (trif luoromethyl) benzyl] -N"- (5-

raet±iyl-[1,2,4]oxadiazol-3-yl)amino]methyl}indan-5-yl)-N-
ethylami no]methyl}cyclohexanecarboxylic acid,
5-[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"- (1-methyl-lH-
pyrazol-3-yl)amino]methyl}-4-trifluoromethoxyphenyl)-N-
ethylaminojpentanoic acid hydrochloride,
5-[N-(2-{[N"-13,5-bis(trifluoromethyl)benzyl]-N"- (1-methyl-lH-
pyrazol-3-yl)amino]methyl}-4-trifluoromethylphenyl)-N-
ethylamino]p>entanoic acid hydrochloride,
5-[N-{2-{[N"-{3-cyano-5-trifluoromethylbenzyl)-N"-(1-raethyl-
lH-pyrazol-3-yl)amino]methyl}-4-trifluoromethylphenyl)-N-
ethylaainojpentanoic acid hydrochloride,
5-[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-
tetrazol-5-yl)amino]methyl}-4-trifluoromethylphenyl)-N-
ethylaiaino]pentanoic acid hydrochloride,
5-[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"- (2-ethyl-2H-
tetrazol-5-yl)amino]methyl}indan-5-yl)-N-ethylamino]pentanoic
acid hydrochloride,
5-{N-[6-({N"-[3,5-bis(trifluoromethyl)benzyl]-N"-[2-(2-
hydroxyethyl)-2H-tetrazol-5-yl]amino}methyl)indan-5-yl]-N-
ethylamino}pentanoic acid hydrochloride,
5-[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-
tetrazol-5-yl)amino]methyl}-4-trifluoromethoxyphenyl)-N-
ethylamino]pentanoic acid hydrochloride,
5-[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-raethyl-2H-
tetrazol-5-yl)amino]methyl}indan-5-yl)-N-ethylamino]-2,2-
dimethylpentanoic acid hydrochloride,
6-[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-
tetrazol-5-yl) amino]methyl}indan-5-yl)-N-ethylamino]hexanoic
acid hydrochloride,
5-[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-raethyl-2H-
tetrazol-5-yl) amino]methyl}indan-5-yl) -N-ethylamir.o]-3 ,3-
dimeiiylpentanoic acid hydrochloride,
rrans-4-{[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-

ei:hyl-2H-tetrazol-5-yl) ainino]met±iyl}indan-5-yl)-N-et±iylaniino]met±iyl}cyclohexanecarboxylic acid hydrochloride, (l-{2-[N-{6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-raerhyl-2ii-tet:razol-5-yl) amino]met±iyl}indan-5-yl) -N-et-hylaminoJet±iyl}cyclopentyl) acetic acid hydrochloride, trans-4-({N-[6-({N"-[3,5-bis(trifluoromethyl)benzyl]-N"-[2-(2-hydroxyethyl)-2H-tetrazol-5-yl]amino}methyl) indan-5-yl]-N-ethylamino}met±iyl) cyclohexanecarboxylic acid, t:rans-4-{ [N-{2-{ [N"-[3,5-bis (trifluoromethyl) benzyl]-N"- (2-methyl-2H-tetrazol-5-yl)amino]methyl}-4-trifiucromethylphenyl)-N-
ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride, (l-{2-[N-(3-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-raethyl-2H-tetrazol-5-yl)amino]methyl}-5,6,7,8-tetrahydronaphthalen-2-yl)-N-ethylamino]ethyl}cyclopentyl)acetic acid,
trans-4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-4-trifluoromethoxyphenyl)-N-
ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride, trans-4-{[N-(3-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-ethyl-2H-tetrazol-5-yl)amino]methyl}-5,6,7,8-tet:rahydronaphthalen-2-yl)-N-
ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride, trans-4-{{N-[3-({N"-[3,5-bis(trifluoromethyl)benzyl]-N"-[2-(2-hydroxyethyl)-2H-tetrazol-5-yl]amino}methyl)-5,6,7,8-tetrahydronaphthalen-2-yl]-N-
ethylaraino}methyl)cyclohexanecarboxylic acid hydrochloride, l-{3-[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}indan-5-yl)-N-ethylamino]propyl}cyclohexanecarboxylic acid hydrochloride, 5-[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(1-methyl-lH-pyrazol-3-yl)amino]methyl}indan-5-yl)-N-ethylamino]-3,3-

dimetiylpentanoic acid,
5-[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(5-methyl-[1,2,4] oxadiazol-3-yl) amino] met±iyl} indan-5-yl) -N-et±iylamino] -3,3-dimet±iylpentanoic acid hydrochloride,
5-[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-4-trifluoromethoxyphenyl)-N-ethylamino3-3,3-dimethylpentanoic acid hydrochloride, 5-[N-{2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-raethyl-2H-tetrazol-5-yl)amino]methyl}-4-trifluoromethylphenyl)-N-ethylamino]-3,3-dimethylpentanoic acid hydrochloride, traiis-4-{ [N-(2-{ [N"-[3,5-bis (trifluoromethyl) benzyl]-N"-(1-methyl-lH-pyrazol-3-yl)amino]methyl}-4-trifluorcxnethoxyphenyl) -N-
ethylamino]methyl}cyclohexanecarboxylie acid hydrochloride, 5-[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(1-methyl-lH-pyrazol-3-yl)amino]methyl}-4-trifluoromethoxyphenyl)-N-ethylamino]-3,3-dimethylpentanoic acid hydrochloride, 5-[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(5-methyl-[1,2,4]oxadiazol-3-yl) amino]methyl}-4-trifluoromethoxyphenyl)-N-ethylamino]-3,3-dimethylpentanoic acid hydrochloride, trans-4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(5-methyl-[1,2,4]oxadiazol-3-yl)amino]methyl}-4-trifluoromethoxyphenyl)-N-
ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride, 6-[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-4-trifluoromethoxyphenyl)-N-ethylamino]hexanoic acid hydrochloride,
trans-(4-{[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}indan-5-yl)-N-ethylaraino]methyl}cyclohexyl)acetic acid hydrochloride, 6-[N-(5-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}indan-5-yl)-N-ethylamino]-4,4-dimerhylhexanoic acid hydrochloride.

6-[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-
t-e-crazol-S-yl) amino]met±iyl}indan-5-yl) -N-etJiylamino]-3,3-
dimetiylhexanoic acid hydrochloride,
5-[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-{2-methyl^2H-
tetrazol-5-yl) ainino]methyl} indan-5-yl) -N-ethylamino]-4 , 4-
dimethylpentanoic acid hydrochloride,
trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
methyl-2H-tetrazol-5-yl)amino]methyl}-4-
trifluorcxnethoxyphenyl)-N-ethylamino]methyl}cyclohexyl)acetic
acid hydrochloride,
6-[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-
tetrazol-5-yl)amino]methyl}-4-trifluoromethoxyphenyl)-N-
ethylamino]-4,4-dimethylhexanoic acid hydrochloride,
6-[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-
tetrazol-5-yl)amino]methyl}-4-trifluoromethylphenyl)-N-
ethylamino]-4,4-dimethylhexanoic acid hydrochloride,
trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
methyl-2H-tetrazol-5-yl)amino]methyl}-4-
trifluoromethylphenyl)-N-ethylamino]methyl}cyclohexyl)acetic
acid hydrochloride,
trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
methyl-2H-tetrazol-5-yl)amino]methyl}-4-
trif luorcanethoxyphenyl) -N-
ethylamino]methyl}cyclohexyl)methanol hydrochloride,
6-[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methy1-2H-
tetrazol-5-yl)amino]methyl}indan-5-yl)-N-ethylaraino]-5,5-
dimethylhexanoic acid hydrochloride,
trans-4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
methyl-2H-tetrazol-5-yl)amino]methy1}-4-
trifluoromethoxyphenyl)-N-
propylamino]methyl}cyclohexanecarboxylic acid hydrochloride,
rrans-4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
merhyl-2K-tetrazol-5-yl)amino]methyl}-4-

trifluoromethoxyphenyl)-N-
isobutylamino]methyl}cyclohexanecarboxylic acid hydrochloride,
t:rans-4-{ [N-(2-{ [N"-[3,5-bis (trif luororaethyl) benzyl]-N"-(2-
inethyl-2E-tetrazol-5-yl) amino]methyl}-4-
trifluoromethoxyphenyl)-N-
ethylamino]methyl}cyclohexanecarboxylie acid amide,
trans-4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
methyl-2H-tetrazol-5-yl)amino]methyl}-4-
trif luorcxnethoxyphenyl) -N-
ethylamino]methyl}cyclohexanecarboxylic acid methylamide,
trans-4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
methyl-ZH-tetrazol-S-yl)amino]methyl}-4-
trifluoromethoxyphenyl)-N-
ethylamino]methyl}cyclohexanecarboxylic acid dimethylamide,
trans-4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(4-
chlorophenyl)amino]methyl}-4-trifluoromethoxyphenyl)-N-
ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride,
trans-4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(p-
tolyl)amino]methyl}-4-trifluoromethoxyphenyl)-N-
ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride,
trans-4-{[N-(2-{[N"-f3,5-bis(trifluoromethyl)benzyl]-N"-(m-
tolyl) amino]methyl}-4-trifluoromethoxyphenyl)-N-
ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride,
trans-4-{[N-(2-{[N"-(3,5-dichlorobenzyl)-N"-(2-methyl-2H-
tetrazol-5-yl)amino]methyl}-4-trifluoromethoxyphenyl)-N-
ethylaraino]methyl}cyclohexanecarboxylic acid hydrochloride,
crans-4-{[N-ethyl-N-(2-{[N"-(2-methyl-2H-tetrazol-5-yl)-N"-(3-
Tiethyl-5-trifluoromethylbenzyl) amino]methyl}-4-
trifluoromethoxyphenyl)amino]methyl}cyclohexanecarboxylic acid
tiydrochloride,
trans-4-{[N-(2-{[N"-(3-chloro-5-trifluoromethylbenzyl)-N"-(2-
Tieiihyl-2H-rerrazol-5-yl) amino]methyl}-4-
crifluoromethoxyphenyl)-N-

^thylaniino]methyl}cyclohexanecarboxylie acid hydrochloride,
trans-4-{[N-ethyl-N-(2-{[N"-(2-methyl-2H-tetrazol-5-yl)-N"-(3-
nitro-S-trifluoromethylbenzyl)amino]methy1}-4-
trifluoromethoxyphenyl)amino]methyl}cyclohexanecarboxylic acid
hydrochloride,
trans-(4-{[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
methyl-2H-tetrazol-5-yl)amino]methyl}-2,2-
difluorobenzo[1,3]dioxol-5-yl)-N-
ethylamino]methyl}cyclohexyl)methanol hydrochloride,
trans-(4-{[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
methyl-2H-tetrazol-5-yl)amino]methyl}-2,2-
difluorobenzo[1,3]dioxol-5-yl)-N-
ethylamino]methyl}cyclohexyl)acetic acid hydrochloride,
trans-3-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
methyl-2H-tetrazol-5-yl)amino]methyl}-4-
trifluoromethoxyphenyl)-N-
ethylamino]methyl}cyclohexyl)propionic acid hydrochloride,
trans-(4-{[N-(7-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
methyl-2H-tetrazol-5-yl)amino]methyl}-2,2,3,3-tetrafluoro-2,3-
dihydrobenzo[1,4]dioxin-6-yl)-N-
ethylamino]methyl}cyclohexyl)methanol hydrochloride,
trans-(4-{[N-(7-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
methyl-2H-tetrazol-5-yl)amino]methyl}-2,2,3,3-tetrafluoro-2,3-
dihydrobenzo[1,4]dioxin-6-yl)-N-
ethy1ami no]methyl}cyclohexyl)acetic acid hydrochloride,
trans-2-(4-{[N-(7-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
methyl-2H-tetrazol-5-yl)amino]methyl}-2,2,3,3-tetrafluoro-2,3-
dihydrobenzo[1,4]dioxin-6-yl)-N-
ethylamino]methyl}cyclohexyl)acetamide hydrochloride,
trans-N-[3,5-bis(trifluoromethyl)benzyl]-N-{2-[N"-ethyl-N"-(4-
(methoxymethy1)cyclohexylmethyl) amino]-5-
rrifluoromethoxybenzyl}-(2-raethyl-2H-tetrazol-5-yl)amine
hydrochloride,

rrans-2-{4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
inetliyl-2H-tetrazol-5-yl) amino]methyl}-4-
rrifluoromet±ioxyphenyl) -N-et±iylamino]met±iyl}cyclohexyl) ethanol
hydrochloride,
■Lrans-(4-{ [N-(2-{ [N"-[3 , 5-bis (trifluoromethyl) benzyl]-N"-(2-
methyl-2H-tetrazol-5-yl)amino]methyl}-4-methy1-5-
trifluorcanethylphenyl)-N-ethylamino]methyl}cyclohexyl)methanol
hydrochloride,
trans-{4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
raethyl-2H-tetrazol-5-yl)amino]methyl}-5-methyl-4-
mf luoromethylphenyl) -N-ethylamino] me thy l}cyclohexyl) acetic
acid hydrochloride,
trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
methyl-2H-tetrazol-5-yl)amino]methyl}-4-methyl-5-
trifluoromethylphenyl)-N-ethylamino]methyl}cyclohexyl)acetic
acid hydrochloride,
trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
raethyl-2H-tetrazol-5~yl)amino]methyl}-4-
trifluoromethoxyphenyl)-N-
ethylamino]methyl}cyclohexylmethyl)phosphonic acid,
trans-4-{[N-(2-{[N"-(3-bromo-5-trifluoromethylbenzyl)-N"-(2-
methyl-2H-tetrazol-5-yl)amino]methyl}-4-
trifluoromethoxyphenyl)-N-
ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride,
trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
tnethyl-2H-tetrazol-5-yl)aminolmethyl}-4-bromophenyl)-N-
ethylamino]methyl}cyclohexyl)methanol hydrochloride,
trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
methyl-2H-tetrazol-5-yl)amino]methyl}-4-bromophenyl)-N-
ethylamino]methyl}cyclohexyl)acetic acid hydrochloride,
trans-(4-{[N-{2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
me"Lhyl-2H-tetrazol-5-yl) amino]methyl}-4-chloro-5-e"Chyiphenyl) -
N-ethylamino]methyl}cyclohexyl)raerhanol hydrochloride.

trans-4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(4-
metioxyphenyl) amino]inethyl}-4-trifluoromethoxyph.enyl) -N-
et±iylamiiio]met±Lyl}cyclohexanecarboxylic acid hydrochloride,
•trans-(4-{ [N-(2-{ [N"-[3,5-bis (trifluoromethyl) benzyl]-N"-(2-
methyl-2H-tetrazol-5-yl)amino]methyl}-5-methoxy-4-
methyIphenyl)-N-ethylamino]methyl}cyclohexyl)methanol
hydrochloride,
trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
raethyl-2H-tetrazol-5-yl)amino]methyl}-4,5-dimethyIphenyl)-N-
ethylamino]methyl}cyclohexyl)acetic acid hydrochloride,
trails-(4-{ IN-(2-{ [N"-[3 , 5-bis (trifluoromethyl) benzyl]-N"-(2-
methyl-2H-tetrazol-5-yl)amino]methyl}-4-
trif luorcxnethylthiophenyl) -N-
ethylamino]methyl}cyclohexyl)acetic acid hydrochloride,
trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
methyl-2H-tetrazol-5-yl)amino]methy1}-4-chloro-5-ethyIphenyl)-
N-ethylamino]methyl}cyclohexyl)acetic acid hydrochloride,
trans-(4-{EN-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
raethyl-2H-tetrazol-5-yl)amino]methyl}-4-
trifluoromethyIphenyl)-N-propylamino]methyl}cyclohexyl)acetic
acid hydrochloride,
trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
methyl-2H-tetrazol-5-yl)amino]methyl}-5-methoxy-4-
methyIphenyl)-N-ethylamino]methyl}cyclohexyl)acetic acid
hydrochloride,
trans-4-({N-[2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
tnethyl-2H-tetrazol-5-yl) amino]methyl}-4- (2,2 , 2-
trifluoroethyl)phenyl]-N-
ethylamino}methyl)cyclohexanecarboxylic acid hydrochloride,
trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
[nethyl-2H-tetrazol-5-yl) araino]methyl}-5-raethyl-4-
trifluoromethyIphenyl)-N-propyiamino]methyl}cyclohexyl)acetic
acid hydrochloride.

trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-inel±iyl-2H-tetrazol-5-yl) amino ] me thy 1}-4-
trifluoromethoxyphenyl) -N-propylainino]methyl}cyclohexyl) acetic acid hydrochloride,
Lrans-4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(4-athylphenyl)aminojmethyl}-4-trifluoromethoxyphenyl)-N-2thylamino]methyl}cyclohexanecarboxylic acid hydrochloride, trans-4-{[N-(2-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-(2-nethyl-2H-tetrazol-5-yl)amino]methyl1-4-crif luoromethoxyphenyl) -N-
sthylamino]methyl}cyclohexanecarboxylic acid hydrochloride, Lrans-4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(4-Lsopropenylphenyl)amino]methyl}-4-trifluoromethoxyphenyl)-N-sthylamino]methyl}cyclohexanecarboxylic acid, :rans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(p-lolyl)amino]methyl}-4-trifluoromethoxyphenyl)-N-^thylaraino]methyl}cyclohexyl)acetic acid dihydrochloride, :rans-(4-{[N-{2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(5-aethyl-[1,2,4]oxadiazol-3-yl)amino]methyl}-4-
:rifluoromethoxyphenyl)-N-ethylamino]methyl}cyclohexyl)acetic icid hydrochloride,
:rans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(5-:iethyl- [1, 2 ,4] oxadia2ol-3-yl) amino]methyl}-5-methyl-4-:rifluoromethylphenyl)-N-ethylamino]methyl}cyclohexyl)acetic icid hydrochloride,
:rans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(5-lethyl-[1,2,4]oxadiazol-3-yl)amino]methyl}-5-methyl-4-:rifluoromethylphenyl)-N-propylamino]methyl}cyclohexyl)acetic icid hydrochloride,
;rans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-iethyl-2H-tetrazol-5-yl)amino]methyl}-5-methy1-4-:rifluoromethylphenyl)-N-propylamino]methyl}cyclohexyi)acetic Lcid,

trans-(4-{ [N-(2-{ [N"-[3,5-bis (trifluorometJiyl) benzyl]-N"-(2-
nieT±iyl-2H-tetrazol-5-yl) ainino]methyl}-4-met±iyl-5-
rrifluorometiylphenyl) -N-ethylamino]met±Lyl}cyclohexyl) acetic
acid,
trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
niethyl-2H-tetrazol-5-yl) amino]methyl }-5-methy 1-4-
trif luorcxoethyIphenyl) -N-ethylamino] methyl }cyclohexyl) acetic
acid methanesulfonate,
ethyl trans-(4-{ [N-(2-{ [N"-[3, 5-bis (trif luorc«nethyl) benzyl]-
N"- (2-methyl-2H-tetrazol-5-yl)amino]methyl}-5-methyl-4-
trifluororaethylphenyl)-N-ethylamino]methyl}cyclohexyl)acetate
and
trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
raethyl-2H-tetrazol-5-yl)amino]methyl}-5-methyl-4-
trifluoromethylphenyl)-N-ethylamino]methyl}cyclohexyl)acetic
acid
or a prodrug thereof or a pharmaceutically acceptable salt
thereof.
[12] The dibenzylamine compound of the above-mentioned [1],
which is selected from the group consisting of
trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
methyl-2H-tetrazol-5-yl)amino]methyl}-4-
trifluoromethoxyphenyl)-N-ethylamino]methyl}cyclohexyl)acetic
acid hydrochloride,
trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
methyl-2H-tetrazol-5-yl)amino]methyl}-4-
trifluoromethylphenyl)-N-ethylamino]methyl}cyclohexyl)acetic
acid hydrochloride,
trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
methyl-2H-tetrazol-5-yl)amino]methyl}-5-raethyl-4-
trifluoromethylphenyl)-N-ethylamino]methyl}cyclohexyl)acetic
acid hydrochloride,
trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-

raet±Lyl-2H-tetrazol-5-yl) amino]met±iyl}-4-met±iyl-5-txifluoromethylphenyl)-N-et±iylamino]methyl}cyclohexyl)acetic acid hydrochloride,
rrans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-raethyl-2H-tetrazol-5-yl)amino]methyl}-4-
trifluoromethylphenyl)-N-propylamino]methyl}cyclohexyl)acetic acid hydrochloride,
-rans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-merhyl-2H-tetrazol-5-yl)amino]methyl}-5-methyl-4-rrifluoromethylphenyl)-N-propylamino]methyl}cyclohexyl)acetic acid hydrochloride,
trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-4-
trifluoromethoxyphenyl)-N-propylamino]methyl}cyclohexyl)acetic acid hydrochloride,
trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-5-methyl-4-trifluoromethylphenyl)-N-propylamino]methyl}cyclohexyl)acetic acid,
trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-" methyl-2H-tetrazol-5-yl)amino]methyl}-4-methyl-5-trifluoromethylphenyl)-N-ethylamino]methyl}cyclohexyl)acetic acid and
trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)ami no]methyl}-5-methyl-4-trifluoromethylphenyl)-N-ethylaraino]methyl}cyclohexyl)acetic acid methanesulfonate
or a prodrug thereof or a pharmaceutically acceptable salt thereof.
[13] The dibenzylamine compound of the above-mentioned [2], which is selected from the group consisting of N-[3-(N"-cyclopentylmethyl-N"-ethylamino)-5,6,7,8-rerrahydronaphthalen-2-ylmetiiyl] -N- [3,5-

bis (trifluoromethyl) benzyl]- (2-met±iyl-2H-tetrazol-5-yl) amine, 3-{[N-[3-(N"-cyclopentylmethyl-N"-ethylamino)-5,6,7,8-t:etrahydronaphthalen-2-ylmet±:yl] -N- (2-methyl-2H-tetrazol-5-yl)amino]methyl}-5-trifluoromethylbenzonitrile, N- [3 , 5-bis (trif luorometiiyl) benzyl] -N- [6- (N"-cyclopentylmethyl-N"-ethylamino) indan-5-ylmethyl] - (2-met±iyl-2H-tetrazol-5-y 1)amine,
N-[3, 5-bis (trif luorometiiyl) benzyl]-N- [6- (N"-cyclopentylmethyl-N"-et±iylamino) indan-5-ylmet±iyl] - (2-methyl-2H-t:etrazol-5-yl)amine hydrochloride,
N- [6- {N"-cyclopentylmethyl-N"-etliylamino) indan-5-ylmethyl] -N-(2H-retjrazol-5-yl) - [3 ,5-bis (trif luorometiiyl) benzyl] amine, N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-N-[3,5-bis(trifluoromethyl)benzyl]-(pyrimidin-2-yl)amine
hydrochloride,
N-[6- (N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-N-[3,5-bis(trifluoromethyl)benzyl]-(5-methyl-lH-pyrazol-3-
yl)amine,
3-{[N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-
ylmethy1]-N-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-5-
trifluoromethylbenzonitrile,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-
N"-ethylamino)indan-5-ylmethyl]-(2-ethyl-2H-tetrazol-5-
yl)amine,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-
N"-ethylamino)indan-5-ylmethyl]-(1-methyl-lH-[1,2,4]triazol-3-
yl)amine,
3-({N-[6-(N"-cyclopentylmethyl-N"-ethylamino) indan-5-
ylmethyl]-N-phenylamino}methyl)-5-trifluoromethylbenzonitrile,
3-{[N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-
ylmethyl]-N-(4,5-dimethyl-thiazol-2-yl)amino]methyl}-5-
rrifluoromethylbenzonitrile,
N- [3,5-bis(rrifluoromethyl)benzyl]-N-[6-(N"-cyclopentyimethyl-

N"-et±iylamino) indan-5-ylmethyl] - (thiazol-2-yl) amine hydrochloride,
3-({N-[6-(N"-cyclopentylmethyl-N"-etJiylainino) indan-5-yImetiyl]-N- (t±Liazol-2-yl) amino}metJiyl) -5-trifluoromethylbenzonitrile hydrochloride,
N-[3,5-bis (trifluoromet±iyl)benzyl]-N- [6- (N"-cyclopentylmetJiyl-N"-ethylamino)indan-5-ylmetliyl]-(oxazol-2-yl) amine hydrochloride,
N-[3,5-bis(trifluoromet±iyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-eT±iylamino) indan-5-ylmethyl] - (5-methylthiazol-2-yl) amine hydrochloride,
N- [3,5-bis (trif luoromethyl) benzyl]-N- [6- (N"-cyclopentylmetliyl-N"-ethylamino) indan-5-ylmethyl] - (4-methylt±iiazol-2-yl) amine hydrochloride,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino) indan-5-ylmethyl]-(4,5-dimethylthiazol-2-yl)amine hydrochloride,
3-{[N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-N-(5-methylthiazol-2-yl)amino]methyl}-5-trifluoromethylbenzonitrile hydrochloride, 3-{[N-[6-(N"-cyclopentylraethyl-N"-ethylamino)indan-5-ylmethyl]-N-(4-methylthiazol-2-yl)amino]methyl}-5-trifluoromethylbenzonitrile hydrochloride,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino) i. ndan-5-ylmethyl] - (4-methyloxazol-2-yl) amine hydrochloride,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-(3-methylisothiazol-5-yl)amine hydrochloride,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-erhylamino)indan-5-ylraethyl]-(5-methylisoxazol-3-yl)amine hydrochloride, N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-

N"-et±iylainino) indan-5-ylmethyl] - (3-methylisoxazol-5-yl) amine hydrochloride,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-erhylamino) indan-5-ylinethyl] - (l-methyl-lH-pyrazol-3-yl)amine hydrochloride,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-(l-methyl-lH-pyrazol-4-yl)amine hydrochloride,
N-[3,5-bis (trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-(5-methyl-[1,3,4]thiadiazol-2-yI)amine hydrochloride,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-(5-methyl-[1,3,4]oxadiazol-2-yl)amine hydrochloride,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-pyridin-3-ylamine hydrochloride,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-pyridin-2-ylamine hydrochloride,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[2-(N"-cyclopentylmethyl-N"-ethylaraino)-5-trifluoromethylbenzyl]-(2-methyl-2H-tetrazol-5-yl)amine hydrochloride and
3-{[N-[2-(N"-cyclopentylraethyl-N"-ethylamino)-5-trifluoromethylbenzyl]-N-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-5-trifluoromethylbenzonitrile hydrochloride or a prodrug thereof or a pharmaceutically acceptable salt thereof.
[14] A pharmaceutical composition comprising the dibenzylamine compound of any of the above-mentioned [1] to [13] or a prodrug thereof or a pharmaceutically acceptable salt rhereof, and a pharmaceutically acceptable carrier. [15] A CETP activity inhibitor comprising a dibenzylamine

ccsnpound of any of the above-mentioned [1] to [13] or a prodxug thereof or a pharmaceutically acceptable salt thereof as an active ingredient.
[16] A therapeutic agent or a prophylactic agent for hyperlipidemia, which comprises a dibenzylamine compound of any of the above-mentioned [1] to [13] or a prodrug thereof or a pharmaceutically acceptable salt thereof as an active ingredient.
[17] A method for treating or preventing hyperlipidemia, which comprises administering a dibenzylamine compound of any of the above-^nentioned [1] to [13] or a prodrug thereof or a pharmaceutically acceptable salt thereof to a mammal. [18] Use of a dibenzylamine compound of any of the above-mentioned [1] to [13] or a prodrug thereof or a pharmaceutically acceptable salt thereof for the production of a therapeutic agent or a prophylactic agent for hyperlipidemia. [19] A therapeutic agent or a prophylactic agent for arteriosclerosis, which comprises a dibenzylamine compound of any of the above-mentioned [1] to [13] or a prodrug thereof or a pharmaceutically acceptable salt thereof as an active ingredient.
[20] A method for treating or preventing arteriosclerosis, which comprises administering a dibenzylamine compound of any of the above-mentioned [1] to [13] or a prodrug thereof or a pharmaceutically acceptable salt thereof to a mammal. [21] Use of a dibenzylamine compound of any of the above-mentioned [1] to [13] or a prodrug thereof or a pharmaceutically acceptable salt thereof for the production of a therapeutic agent or a prophylactic agent for arteriosclerosis.
[22] The pharmaceutical composition of the c±>ove-mentioned [14], which is used in combination with a different therapeutic agent for hyperlipidemia.

[23] The pharmaceutical composition of the above-mentioned [22], wherein the different therapeutic agent for hyp>erlipidemia is a statin pharmaceutical agent. [24] The pharmaceutical composition of the above-mentioned [23], wherein the statin pharmaceutical agent is at least one pharmaceutical agent selected from the group consisting of lovastatin, simvastatin, pravastatin, fluvastatin, atorvastatin and cerivastatin.
[25] The pharmaceutical composition of the above-mentioned [14], which is used in combination with a different -±erapeutic agent for obesity.
[26] The pharmaceutical composition of the above-mentioned [25], wherein the different therapeutic agent for obesity is mazindol.
[27] The pharmaceutical composition of the above-mentioned [14], which is used in combination with a different therapeutic agent for diabetes.
[28] The phaimaceutical composition of the above-mentioned [27], wherein the different therapeutic agent for diabetes is at least one pharmaceutical agent selected from the group consisting of an insulin preparation, a sulfonylurea, an insulin secretagogue, a sulfonamide, a biguanide, an a glucosidase inhibitor and an insulin sensitizer. [29] The pharmaceutical composition of the above-mentioned [28], wherein the different therapeutic agent for diabetes is at least one pharmaceutical agent selected from the group consisting of insulin, glibenclamide, tolbutamide, glyclopyramide, acetohexamide, glimepiride, tolazamide, gliclazide, nateglinide, glybuzole, metformin hydrochloride, buformin hydrochloride, voglibose, acarbose and pioglitazone hydrochloride.
[30] The pharmaceutical composirion of the above-menrioned [14], which is used in combina"cion with a different

"therapeutic agent for hypertension,.
[31] The pharmaceutical composition of the above-mentioned [30], wherein the different therapeutic agent for hypertension is ar least one pharmaceutical agent selected from the group consisting of a loop diuretic, an angiotensin converting enzyme inhibitor, an angiotensin II receptor antagonist, a Ca antagonist, a p blocker, an a,^ blocker and an a blocker. [32] The pharmaceutical composition of the above-mentioned [31], wherein the different therapeutic agent for hypertension is at least one pharmaceutical agent selected from the group consisting of a furosemide sustained-release preparation, captopril, a captopril sustained-release preparation, enalapril maleate, alacepril, delapril hydrochloride, cilazapril, lisinopril, benazepril hydrochloride, imidapril hydrochloride, temocapril hydrochloride, quinapril hydrochloride, trandrapril, perindopril erbumine, losartan potassium, candesartan cilexetil, nicardipine hydrochloride, a nicardipine hydrochloride sustained-release preparation, nilvadipine, nifedipine, a nifedipine sustained-release preparation, benidipine hydrochloride, diltiazem hydrochloride, a diltiazem hydrochloride sustained-release preparation, nisoldipine, nitrendipine, manidipine hydrochloride, barnidipine hydrochloride, efonidipine hydrochloride, amlodipine besylate, felodipine, cilnidipine, aranidipine, propranolol hydrochloride, a propranolol hydrochloride sustained-release preparation, pindolol, a pindolol sustained-release preparation, indenolol hydrochloride, carteolol hydrochloride, a carteolol hydrochloride sustained-release preparation, bunitrolol hydrochloride, a bunitrolol hydrochloride sustained-release preparation, atenolol, acebutolol hydrochloride, raetoprolol tartrate, a raetoprolol "arrrare sustained-release preparation, nipradilol, penbutolol sulfare, tilisolol hydrochloride, carvedilol, bisoprolol

ftimarate, beta-xolol hydrochloride, celiprolol hydrochloride, bopindolol malonate, bevantolol hydrochloride, labetalol hydrochloride, arotinolol hydrochloride, amosulalol hydrochloride, prazosin hydrochloride, terazosin hydrochloride, doxazosin mesylate, bunazosin hydrochloride, a bunazosin hydrochloride sustained-release preparation, urapidil and phentolamine mesylate.
[33] The therapeutic agent or a prophylactic agent of the above-mentioned [16], which aims at the treatment or prophylaxis of hyperlipidemia and which is used in combination with a different therapeutic agent for hyperlipidemia. [34] The therapeutic agent or a prophylactic agent of the above-mentioned [33] , wherein the different therap>eutic agent for hyperlipidemia is a statin pharmaceutical agent. [35] The therapeutic agent or a prophylactic agent of the above-mentioned [34], wherein the statin pharmaceutical agent is at least one pharmaceutical agent selected from the group consisting of lovastatin, simvastatin, pravastatin, fluvastatin, atorvastatin and cerivastatin. [36] The therapeutic agent or a prophylactic agent of the above-mentioned [16], which aims at the treatment or prophylaxis of hyperlipidemia and which is used in combination with a different therapeutic agent for obesity. [37] The therapeutic agent or a prophylactic agent of the above-mentioned [36], wherein the different therapeutic agent for obesity is mazindol.
[38] The therapeutic agent or a prophylactic agent of the above-mentioned [16], which aims at the treatment or prophylaxis of hyperlipidemia and which is used in combination with a different therapeutic agent for diaberes. [39] The therapeutic agent or a prophylactic agenr of the above-mentioned [38] , wherein rhe different -iherapeutic agent for diabetes is at least one pharmaceutical agent selected

from the group consisting of an insulin preparation, a sulfonylurea, an insulin secretagogue, a sulfonamide, a biguanide, an a glucosidase inhibitor and an insulin sensitizer.
[40] The therapeutic agent or a prophylactic agent of the above-mentioned [39], wherein the different therapeutic agent for diabetes is at least one pharmaceutical agent selected from the group consisting of insulin, glibenclamide, tolbutamide, glyclopyramide, acetohexamide, glimepiride, tolazamide, gliclazide, nateglinide, glybuzole, metformin hydrochloride, buformin hydrochloride, voglibose, acarbose and pioglitazone hydrochloride.
[41] The therapeutic agent or a prophylactic agent of the above-mentioned [16], which aims at the treatment or prophylaxis of hyperlipidemia and which is used in combination with a different therapeutic agent for hypertension. [42] The therapeutic agent or a prophylactic agent of the above-mentioned [41], wherein the different therapeutic agent for hypertension is at least one pharmaceutical agent.selected from the group consisting of a loop diuretic, an angiotensin converting enzyme inhibitor, an angiotensin II receptor antagonist, a Ca antagonist, a p blocker, an a,p blocker and an a blocker.
[43] The therapeutic agent or a prophylactic agent of the above—mentioned [42], wherein the different therapeutic agent for hypertension is at least one pharmaceutical agent selected from the group consisting of a furosemide sustained-release preparation, captopril, a captopril sustained-release preparation, enalapril maleate, alacepril, delapril hydrochloride, cilazapril, lisinopril, benazepril hydrochloride, imidapril hydrochloride, temocapril hydrochloride, quinapril hydrochloride, trandrapril, perindopril erbumine, losartan potassium, candesartan

cilexeril, nicardipine hydrochloride, a nicardipine hydrochloride sustained-release preparation, nilvadipine, nifedipine, a nifedipine sustained-release preparation, benidipine hydrochloride, diltiazem hydrochloride, a diltiazem hydrochloride sustained-release preparation, nisoldipine, nitrendipine, manidipine hydrochloride, barnidipine hydrochloride, efonidipine hydrochloride, amlodipine besylate, felodipine, cilnidipine, aranidipine, propranolol hydrochloride, a propranolol hydrochloride sustained-release preparation, pindolol, a pindolol sustained-release preparation, indenolol hydrochloride, carteolol hydrochloride, a carteolol hydrochloride sustained-release preparation, bunitrolol hydrochloride, a bunitrolol hydrochloride sustained-release preparation, atenolol, acebutolol hydrochloride, metoprolol tartrate, a metoprolol tartrate sustained-release preparation, nipradilol, penbutolol sulfate, tilisolol hydrochloride, carvedilol, bisoprolol fiomarate, oetaxolol hydrochloride, celiprolol hydrochloride, bopindolol nalonate, bevantolol hydrochloride, labetalol hydrochloride, arotinolol hydrochloride, amosulalol hydrochloride, prazosin lydrpchloride, terazosin hydrochloride, doxazosin mesylate, Dunazosin hydrochloride, a bunazosin hydrochloride sustained-release preparation, urapidil and phentolamine mesylate. [44] The method of the above-mentioned [17] , which aims at the treatment or prophylaxis of hyp>erlipidemia and which is used Ln combination with a different therapeutic agent for lyperlipidemia.
[45] The method of the above-mentioned [44], wherein the iifferent therapeutic agent for hyperlipidemia is a statin Dharmaceutical agent.
[46] The method of the above-mentioned [45], wherein the 3"uarin pharmaceutical agent is at least one pharmaceutical igent selected from the group consisting of lovastatin.

simvastatin, pravastatin, fluvastatin, atorvastatin and cerivastatin.
[47] The method of the above-mentioned [17] , which aims at the treatment or prophylaxis of hyperlipidemia and which is used in combination with a different therapeutic agent for obesity. [48] The method of the above-mentioned [47] , wherein the different therapeutic agent for obesity is mazindol. [49] The method of the above-mentioned [17], which aims at the treatment or prophylaxis of hyperlipidemia and which is used in combination with a different therapeutic agent for diabetes. [50] The method of the above-mentioned [49] , wherein the different therapeutic agent for diabetes is at least one pharmaceutical agent selected from the group consisting of an insulin preparation, a sulfonylurea, an insulin secretagogue, a sulfonamide, a biguanide, an a glucosidase inhibitor and an insulin sensitizer.
[51] The method of the above-mentioned [50], wherein the different therapeutic agent for diabetes is at least one pharmaceutical agent selected from the group consisting of insulin, glibenclamide, tolbutamide, glyclopyramide, acetohexamide, glimepiride, tolazamide, gliclazide, nateglinide, glybuzole, metformin hydrochloride, buformin hydrochloride, voglibose, acarbose and pioglitazone hydrochloride.
[52] The method of the above-mentioned [17], which aims at the treatment or prophylaxis of hyperlipidemia and which is used in combination with a different therapeutic agent for hypertension,
[53] The method of the above-mentioned [52], wherein the different therapeutic agent for hypertension is at least one pharmaceutical agent selected from the group consisting of a loop diuretic, an angiotensin converting enzyme inhibitor, an angiotensin II receptor antagonist, a Ca antagonist, a p

blocker, ^n a,^ blocker and an a blocker. [54] The method of the above-mentioned [53], wherein the different therapeutic agent for hypertension is at least one pharmaceutical agent selected from the group consisting of a furosenide sustained-release preparation, captopril, a captopril sustained-release preparation, enalapril maleate, alacepril, delapril hydrochloride, cilazapril, lisinopril, benazepril hydrochloride, imidapril hydrochloride, temocapril hydrochloride, quinapril hydrochloride, trandrapril, perindopril erbumine, losartan potassium, candesartan cilexetil, nicardipine hydrochloride, a nicardipine hydrochloride sustained-release preparation, nilvadipine, nifedipine, a nifedipine sustained-release preparation, benidipine hydrochloride, diltiazem hydrochloride, a diltiazem hydrochloride sustained-release preparation, nisoldipine, nitrendipine, manidipine hydrochloride, barnidipine hydrochloride, efonidipine hydrochloride, amlodipine besylate, felodipine, cilnidipine, aranidipine, propranolol hydrochloride, a propranolol hydrochloride sustained-release preparation, pindolol, a pindolol sustained-release preparation, indenolol hydrochloride, carteolol hydrochloride, a carteolol hydrochloride sustained-release preparation, bunitrolol hydrochloride, a bunitrolol hydrochloride sustained-release preparation, atenolol, acebutolol hydrochloride, metoprolol tartrate, a metoprolol tartrate sustained-release preparation, nipradilol, penbutolol sulfate, tilisolol hydrochloride, cairvedilol, bisoprolol fumarate, betaxolol hydrochloride, celiprolol hydrochloride, bopindolol malonate, bevantolol hydrochloride, labetalol hydrochloride, arotinolol hydrochloride, amosulalol hydrochloride, prazosin hydrochloride, terazosin hydrochloride, doxazosin mesylate, bunazosin hydrochloride, a bunazosin hydrochloride sustained-release preparation, urapidil and phenrolamine mesylate.

[5 5] The therapeutic agent or a prophylactic agent of the above-mentioned [19], which aims at the treatment or prophylaxis of arteriosclerosis and which is used in combination with a different therapeutic agent for hyp>erlipidemia.
[56] The therapeutic agent or a prophylactic agent of the above-mentioned [55], wherein the different therapeutic agent for hyperlipidemia is a statin pharmaceutical agent. [57] The therapeutic agent or a prophylactic agent of the above-mentioned [56], wherein the statin pharmaceutical agent is at least one pharmaceutical agent selected from the group consisting of lovastatin, simvastatin, pravastatin, fluvastatin, atorvastatin and cerivastatin. [58] The therapeutic agent or a prophylactic agent of the above-mentioned [19], which aims at the treatment or prophylaxis of arteriosclerosis and which is used in combination with a different therapeutic agent for obesity. [59] The therapeutic agent or a prophylactic agent of the above-mentioned [58], wherein the different therapeutic agent for obesity is mazindol.
[60] The therapeutic agent or a prophylactic agent of the above-mentioned [19], which aims at the treatment or prophylaxis of arteriosclerosis and which is used in combination with a different therapeutic agent for diabetes. [61] The therapeutic agent or a prophylactic agent of the above-mentioned [60], wherein the different therapeutic agent for diabetes is at least one pharmaceutical agent selected from the group consisting of an insulin preparation, a sulfonylurea, an insulin secretagogue, a sulfonamide, a biguanide, an a glucosidase inhibitor and an insulin sensitizer.
[62] The therapeutic agenr or a prophylactic agent of the above-mentioned [61] , wherein the different therapeutic agent

for diabetes is at least one pharmaceutical agent selected from the group consisting of insulin, glibenclamide, tolbutamide, glyclopyramide, acetohexamide, glimepiride, tolazamide, gliclazide, nateglinide, glybuzole, metformin hydrochloride, buformin hydrochloride, voglibose, acarbose and pioglitazone hydrochloride.
[63] The therapeutic agent or a prophylactic agent of the above-mentioned [19], which aims at the treatment or prophylaxis of arteriosclerosis and which is used in combination with a different therapeutic agent for hypertension.
[64] The therapeutic agent or a prophylactic agent of the above-mentioned [63], wherein the different therapeutic agent for hypertension is at least one pharmaceutical agent selected from the group consisting of a loop diuretic, an angiotensin converting enzyme inhibitor, an angiotensin II receptor antagonist, a Ca antagonist, a p blocker, an a,p blocker and an a blocker.
[65] The therapeutic agent or a prophylactic agent of the above-mentioned [64], wherein the different therapeutic agent for hypertension is at least one pharmaceutical agent selected from the group consisting of a furosemide sustained-release preparation, captopril, a captopril sustained-release preparation, enalapril maleate, alacepril, delapril hydrochloride, cilazapril, lisinopril, benazepril hydrochloride, imidapril hydrochloride, temocapril hydrochloride, quinapril hydrochloride, trandrapril, perindopril erbumine, losartan potassium, candesartan cilexetil, nicardipine hydrochloride, a nicardipine hydrochloride sustained-release preparation, nilvadipine, nifedipine, a nifedipine sustained-release preparation, benidipine hydrochloride, dilriazem hydrochloride, a diltiazem hydrochloride sustained-release prepararion, nisoldipine.

nitrendipine, manidipine hydrochloride, barnidipine hydrochloride, efonidipine hydrochloride, amlodipine besylate, felodipine, cilnidipine, aranidipine, propranolol hydrochloride, a propranolol hydrochloride sustained-release preparation, pindolol, a pindolol sustained-release prep>aration, indenolol hydrochloride, carteolol hydrochloride, a carteolol hydrochloride sustained-release preparation, bunitrolol hydrochloride, a bunitrolol hydrochloride sustained-release preparation, atenolol, acebutolol hydrochloride, metoprolol tartrate, a metoprolol tartrate sustained-release preparation, nipradilol, penbutolol sulfate, tilisolol hydrochloride, carvedilol, bisoprolol fumarate, betaxolol hydrochloride, celiprolol hydrochloride, bopindolol malonate, bevantolol hydrochloride, labetalol hydrochloride, arotinolol hydrochloride, amosulalol hydrochloride, prazosin hydrochloride, terazosin hydrochloride, doxazosin mesylate, bunazosin hydrochloride, a bunazosin hydrochloride sustained-release preparation, urapidil and phentolamine mesylate. [66] The method of the above-mentioned [20], which aims at the treatment or prophylaxis of arteriosclerosis and which is used in combination with a different therapeutic agent for hyperlipidemia.
[67] The method of the above-mentioned [66], wherein the different therapeutic agent for hyperlipidemia is a statin pharmaceutical agent.
[68] The method of the above-mentioned [67], wherein the statin pharmaceutical agent is at least one pharmaceutical agent selected from the group consisting of lovastatin, simvastatin, pravastatin, fluvastatin, atorvastatin and cerivastatin.
[69] The method of the above-mentioned [20], which aims at the treatment or prophylaxis of arteriosclerosis and which is used in combination with a different therapeutic agent for obesity.

[70] The method of the above-mentioned [69], wherein the different therapeutic agent for obesity is mazindol.
[71] The method of the above-mentioned [20], which aims at the treatment or prophylaxis of arteriosclerosis and which is used in combination with a different therapeutic agent for diabetes.
[72] The method of the above-mentioned [71] , wherein the different therapeutic agent for diabetes is at least one pharmaceutical agent selected from the group consisting of an insulin preparation, a sulfonylurea, an insulin secretagogue, a sulfonamide, a biguanide, an a glucosidase inhibitor and an insulin sensitizer.
[73] The method of the above-mentioned [72], wherein the different therapeutic agent for diabetes is at least one pharmaceutical agent selected from the group consisting of insulin, glibenclamide, tolbutamide, glyclopyramide, acetohexamide, glimepiride, tolazamide, gliclazide, nateglinide, glybuzole, metformin hydrochloride, buformin hydrochloride, voglibose, acarbose and pioglitazone hydrochloride.
[74] The method of the above-mentioned [20], which aims at the treatment or prophylaxis of arteriosclerosis and which is used in combination with a different therapeutic agent for hypertension.
[75] The method of the above-mentioned [74], wherein the different therapeutic agent for hypertension is at least one pharmaceutical agent selected from the group consisting of a loop diuretic, an angiotensin converting enzyme inhibitor, an angiotensin II receptor antagonist, a Ca antagonist, a p blocker, an a,p blocker and an a blocker. [76] The method of the above-mentioned [75] , wherein the different therapeutic agent for hypertension is at least one pharmaceutical agent selected from the group consisring of a furose.Tiide sustained-release preparation, captopril, a

captopril sustained-release preparation, enalapril maleate, alacepril, delapril hydrochloride, cilazapril, lisinopril, benazepril hydrochloride, imidapril hydrochloride, temocapril hydrochloride, quinapril hydrochloride, trandrapril, perindopril erbumine, losartan potassium, candesartan cilexetil, nicardipine hydrochloride, a nicardipine hydrochloride sustained-release preparation, nilvadipine, nifedipine, a nifedipine sustained-release preparation, benidipine hydrochloride, diltiazem hydrochloride, a diltiazem hydrochloride sustained-release preparation, nisoldipine, nitrendipine, manidipine hydrochloride, barnidipine hydrochloride, efonidipine hydrochloride, amlodipine besylate, felodipine, cilnidipine, aranidipine, propranolol hydrochloride, a propranolol hydrochloride sustained-release preparation, pindolol, a pindolol sustained-release preparation, indenolol hydrochloride, carteolol hydrochloride, a carteolol hydrochloride sustained-release preparation, bunitrolol hydrochloride, a bunitrolol hydrochloride sustained-release preparation, atenolol, acebutolol hydrochloride, metoprolol tartrate, a metoprolol tartrate sustained-release preparation, nipradilol, penbutolol sulfate, tilisolol hydrochloride, carvedilol, bisoprolol fumarate, betaxolol hydrochloride, celiprolol hydrochloride, bopindolol malonate, bevantolol hydrochloride, labetalol hydrochloride, arotinolol hydrochloride, amosulalol hydrochloride, prazosin hydrochloride, terazosin hydrochloride, doxazosin mesylate, bunazosin hydrochloride, a bunazosin hydrochloride sustained-release preparation, urapidil and phentolamine mesylate. Detailed Description of the Invention
The definition of each substituent used in the present specification is as follows.
The "halogen atom" is a chlorine atom, a bromine atom, a fluorine atom and the like. For RS R^ R", R\ R", R\ R^°, R"

or R^^, it is preferably a chlorine atom or a fluorine atom, and a preferable halogen atom as a substituent for the C4-10 cycloalkylalkyl group for R", R^, R^^, R^^ or R" is chlorine atom or fluorine atom.
The "02-6 alkenyl group" is a straight chain or optionally branched alkenyl.group having 2 to 6 carbon atoms, such as ethenyl group (vinyl group), 1-propenyl group, 2-propenyl group (allyl group), isopropenyl group, 1-butenyl group, 2-butenyl group, 3-butenyl group, 1-methyl-1-propenyl group, 1-inethyl-2-propenyl group, 2-methyl-2-propenyl group, 1-ethylvinyl group, 1-pentenyl group, 2-pentenyl group, 3-pentenyl group, 4-pentenyl group, 1,2-dimethyl-l-propenyl group, l,2-dimethyl-2-propenyl group, 1-ethyl-l-propenyl group, l-ethyl-2-propenyl group, 1-methyl-l-butenyl group, 1-methyl-2-butenyl group, 2-methyl-l-butenyl group, 1-isopropylvinyl group, 2,4-pentadienyl group, 1-hexenyl group, 2-hexenyl group, 3-hexenyl group, 4-hexenyl group, 5-hexenyl group, 2,4-hexadienyl group, 1-methyl-l-pentenyl group and the like, preferably a straight chain or optionally branched alkenyl group having 2 to 4 carbon atoms. Particularly preferred are ethenyl group, isopropenyl group and 2-methyl-2-propenyl group.
The "Ci-6 alkyl group" is a straight chain or optionally branched alkyl group having 1 to 6 carbon atoms, such as [Tiethyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, sec-butyl group, tert-butyl group, pentyl group, isopentyl group, neopentyl group, tert-pentyl group, hexyl group and the like, preferably a straight chain or optionally branched alkyl group having 1 to 4 carbon atoms. Particularly preferred are methyl group, ethyl group and isopropyl group. R^° and R^""^ are each preferably a methyl group. For R^, R^°, R^^ or R", it is preferably a methyl group or an erhyl group, for R^, R°, R*^, R"^ or R^^, it is preferably an sthyl group, a propyl group or a butyl group, and for R^ or R^°,

it is preferably a met±iyl group or an ethyl group. A preferable Ci-e alkyl group as a substituent for the C4-10 cycloalkylalkyl group for R^, R^, R^\ R^^ or R^^ is a methyl group or an ethyl group. For R^*, it is preferably a methyl group or an ethyl group.
The "Ci-e alkyl group optionally substituted by halogen atoms" is the aforementioned Ci-s alkyl group optionally substituted by the aforementioned halogen atoms, such as nethyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, sec-butyl group, tert-butyl group, pentyl group, isopentyl group, neopentyl group, tert-pentyl group, hexyl group, trifluoromethyl group, 1- or 2-chloroethyl group, 1- or 2-bromoethyl group, 1- or 2-fluoroethyl group, 1-, 2- or 3-chloropropyl group, 1-, 2- or 3-bromopropyl group, 1-, 2- or 3-fluoropropyl group, 1-, 2-, 3- or 4-chlorobutyl group, L-, 2-, 3- or 4-bromobutyl group, 1-, 2-, 3- or 4-fluorobutyl jroup and the like, preferably methyl group, ethyl group or trif luoromethyl group. For R^, R^, R^, R* or R^, it is preferably a methyl group, an ethyl group or a trifluoromethyl jroup.
The "Ci-e alkoxy group" means a straight chain or branched :;hain alkoxy group having 1 to 6 carbon atoms, such as methoxy jroup, ethoxy group, propoxy group, isopropoxy group, butoxy jroup, tert-butoxy group, pentyloxy group, tert-pentyloxy jroup and hexyloxy group. Preferred are methoxy group, ethoxy jroup, isopropoxy group, butoxy group and tert-butoxy group, fhich have 1 to 4 carbon atoms. Particularly preferred are tiethoxy group and ethoxy group. For R^, R^°, R^^ or R", it is preferably a methoxy group, and a preferable Ci-6 alkoxy group is a substituent for the C4-10 cycloalkylalkyl group for R", R^, l"^, R^"^ or R^"^ is a methoxy group or an ethoxy group.
The ""Ci-e alkoxy group optionally substituted by halogen iroms" is the aforementioned Ci-s alkoxy group optionally

substituted by the aforementioned halogen atoms, such as methoxy group, ethoxy group, propoxy group, isopropoxy group, butoxy group, tert-butoxy group, pentyloxy group, tert-pentyloxy group, hexyloxy group, trifluoromethoxy group, 1- or 2-chloroethoxy group, 1- or 2-bromoethoxy group, 1- or 2-fluoroethoxy group, 1-, 2- or 3-chloropropoxy group, 1-, 2- or 3-brcanopropoxy group, 1-, 2- or 3-fluoropropoxy group, 1-, 2-, 3- or 4-chlorobutoxy group, 1-, 2-, 3- or 4-broraobutoxy group, 1-, 2-, 3- or 4-fluorobutoxy group and the like. Preferred are methoxy group, ethoxy group and trifluoromethoxy group. For R^, R* or R^, it is preferably a methoxy group, an ethoxy group or a trifluoromethoxy group.
The "Ci-e alkylthio group optionally substituted by halogen atoms" is one wherein the Ci_6 alkylthio group is optionally substituted by the aforementioned halogen atoms, which is exemplified by methylthio group, ethylthio group, propylthio group, isopropylthio group, butylthio group, tert-butylthio group, pentylthio group, tert-pentylthio group, hexylthio group, trifluoromethylthio group, 1- or 2-chloroethylthio group, 1- or 2-bromoethylthio group, 1- or 2-fluoroethylthio group, 1-, 2- or 3-chloropropylthio group, 1-, 2- or 3-bromopropylthio group, 1-, 2- or 3-fluoropropylthio group, 1-, 2-, 3- or 4-chlorobutylthio group, 1-, 2-, 3- or 4-bromobutylthio group, 1-, 2-, 3- or 4-fluobutylthio group and the like, preferably methylthio group, ethylthio group or trif luoromethylthio group. For R^, R* or R^, it is preferably a methylthio group, an ethylthio group or a trifluoromethylthio group.
The "€4-10 cycloalkylalkyl group" is a C1-3 alkyl group substituted by C3-7 cycloalkyl group. Here, the "Cs-y cycloalkyl group" means a cycloalkyl group having 3 to 7 carbon atoms, which is exemplified by cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group and cycloheptyl group.

Preferred is cycloalkyl group having 3 to 6 carbon atoms, . which is specifically cyclopropyl group, cyclobutyl group, cyclopentyl group or cyclohexyl group. The "C1-3 alkyl group" means a straight chain or optionally branched alkyl group having 1 to 3 carbon atoms, which is exemplified by methyl group, ethyl group, propyl group and isopropyl group. Preferred are methyl group, ethyl group and propyl group.
Concrete examples of the *C4-io cycloalkylalkyl group" include cyclopropyImethy1 group, cyclobutylmethyl group, cyclopentylmethyl group, cyclohexylmethyl group, cycloheptylmethyl group, cyclopentylethyl group (1- or 2-(cyclopentyl)ethyl group), cyclohexylethyl group (1- or 2-(cyclohexyl)ethyl group), cyclopentylpropyl group (1-, 2- or 3-(cyclopentyl)propyl group) and cyclohexylpropyl group (1-, 2- or 3-(cyclohexyl)propyl group). Preferred is cycloalkylalkyl group preferably having 3 to 7 carbon atoms, which is specifically cyclopropylmethyl group, cyclobutylmethyl group, cyclopentylmethyl group or cyclohexylmethyl group. A preferable C4-10 cycloalkylalkyl group for R", R®, R^^, R^^ or R^^ is cyclopentylmethyl group, cyclohexylmethyl group or 2-(cyclopentyl)ethyl group.
The "*acyl group" includes alkylcarbonyl groups such as acetyl group, propionyl group, butyryl group, pivaloyl group and the like; and arylcarbonyl groups such as benzoyl group, naphthoyl and the like. Preferred is acetyl group. For R^, R^°, R^^ or R^^, it is preferably an acetyl group, a preferable acyl group as a substituent for the C4-10 cycloalkylalkyl group for R", R^ R^\ R^^ or R" is acetyl group.
The ""aryl group" is a phenyl group, a naphthyl group, a biphenyl group and the like, with preference given to a phenyl group.
As the ""heterocyclic residue", a 5- to S-membered aromatic heterocyclic group containing, besides carbon atom, 1

ro 4 heteroatoms selected from oxygen atom, sulfur atom, nitrogen atom and the like, a bicyclic or tricyclic heterocyclic group condensed therewith and the like can be mentioned. Examples thereof include pyrrolyl group (1-, 2- or 3-pyrrolyl group), furyl group (2- or 3-furyl group), thienyl group (2- or 3-thienyl group), imidazolyl group (1-, 2-, 4- or 5-imidazolyl group), oxazolyl group (2-, 4- or 5-oxazolyl group), thiazolyl group (2-, 4- or 5-thiazolyl group), pyrazolyl group (1-, 3-, 4- or 5-pyrazolyl group), isoxazolyl group (3-, 4- or 5-isoxazolyl group), isothiazolyl group (3-, 4- or 5-isothiazolyl group), oxadiazolyl group (1,2,4-oxadiazol-3 or 5-yl group, 1,3,4-oxadiazol-2-yl group, 1,2,5-oxadiazol-3-yl group), thiadiazolyl group (l,2,4-thiadiazol-3 or 5-yl group, 1,3,4-thiadiazol-2-yl group, 1,2,5-thiadiazol-3-yl group), triazolyl group (1,2,4-triazol-l, 3, 4 or 5-yl group, 1,2,3-triazol-l, 2 or 4-yl group), indolyl group (1-, 2-, 3-, 4-, 5-, 6- or 7-indolyl group), benzofuryl group (2-, 3-, 4-, 5-, 6- or 7-benzofuryl group), benzothienyl group (2-, 3-, 4-, 5-, 6- or 7-benzothienyl group), benzimidazolyl group (1-, 2-, 4-, 5-, 6- or 7-benzimidazolyl group), benzoxazolyl group (2-, 4-, 5-, 6- or 7-benzoxazolyl group), benzothiazolyl group (2-, 4-, 5-, 6- or 7-benzothiazolyl group), pyridyl group (2-, 3- or 4-pyridyl group), pyridine-1-oxide group (2-, 3- or 4-pyridine-l-oxide group), pyrimidinyl group (2-, 4- or 5-pyrimidinyl group), tetrazolyl group (lH-tetrazol-1 or 5-yl group, 2H-tetrazol-2 or 5-yl group), quinolyl group (2-, 3-, 1-, 5-, 6-, 7- or 8-quinolyl group), isoquinolyl group (1-, 3-, 1-, 5-, 6-, 7- or 8-isoquinolyl group) and the like.
As the "homocyclic ring", for example, an optionally condensed 3- to 7-merabered carbon ring such as Cg-io arene (Cg-io iryl) (e.g., benzene (phenyl), naphthalene (naphthyl) and the Like), C3-7 cycloalkane (cycloalkyl) (e.g., cyclopropane (cyclopropyl), cyclobutane (cyclobutyl), cyclopentane

(cyclopentyl), cyclohexane (cyclohexyl), cycloheptane (cycloheptyl) etc.), C3-7 cycloalkene (C3-7 cycloalkenyl group) (e.g., cyclopropene (cyclopronyl), cyclobutene (cyclobutenyl), cyclopentene (cyclopentenyl), cyclohexene (cyclohexenyl), cycloheptene (cycloheptenyl) etc.) and the like, and the like are used. The parenthesis following each name of the hcxnocyclic ring shows a homocyclic group corresponding to the homocyclic ring.
As the substituent that the above-mentioned homocyclic ring may have, for example, (1) a Ci_6 alkyl group optionally substituted by halogens (particularly, Ci_6 alkyl group substituted by halogens is preferable) , (2) a C3-10 cycloalkyl group, (3) a C2-10 alkenyl group, (4) a C2-io alkynyl group, (5) a Ce-io aryl group, (6) a C7-20 aralkyl group, (7) a nitro group, (8) a hydroxy group, (9) a mercapto group, (10) a 0x0 group, (11) a thioxo group, (12) a cyano group, (13) a carbamoyl group, (14) a carboxyl group, (15) a Ci-e alkoxycarbonyl group (e.g., methoxycarbonyl group, ethoxycarbonyl group etc.), (16) a sulfo, (17) a halogen atom, (18) a Ci-e alkoxy group, (19) a Cs-io aryloxy group (e.g., phenoxy group etc.), (20) a Ci_6 acyloxy group (e.g., acetoxy, propionyloxy) , (21) a Ci-s alkylthio group (e.g., methylthio group, ethylthio group, n-propylthio group, isopropylthio group, n-butylthio group, tert-butylthio group etc.), (22) a Ce-io arylthio group (e.g., phenylthio group etc.), (23) a Ci.-e aJ-kylsulfinyl group (e.g., methylsulfinyl group, ethylsulfinyl group etc.), (24) a Ce-io arylsulfinyl group (e.g., phenylsulfinyl group etc.), (25) a Ci_6 alkylsulfonyl group (e.g., methylsulfonyl group, ethylsulfonyl group etc.), (26) a Ce-io arylsulfonyl group (e.g., phenylsulfonyl group etc.), (27) an amino group, (28) a Ci-g acylamino group (e.g., acetylamino group, propionylamino group ere), (29) a mono- or di-Ci-4 alkylamino group (e.g., methylamino group, ethylamino group, n-propylairdno group,

isopropylamino group, n-butylamino group, dimethylamino gr diethyl amino group etc.), (30) a C3-8 cycloalkylamino group
(e.g., cyclopropylamino group, cyclobutylamino group,
cyclopentylamino group, cyclohexylamino group etc.), (31) a Ce-10 arylamino group (e.g., anilino etc.), (32) a Ci-e alkanoyl group (e.g., formyl group, acetyl group, hexanoyl group etc.),
(33) Ce-io arylcarbonyl group (e.g., benzoyl group etc.), (34) a 5- or 6-membered heterocyclic group containing, besides carbon atcan, 1 to 4 heteroatoms selected from oxygen, sulfur, nitrogen and the like (e.g., 2- or 3-thienyl group, 2- or 3-furyl group, 3-, 4- or 5-pyrazolyl group, 2-, 4- or 5-rhiazolyl group, 3-, 4- or 5-isothiazolyl group, 2-, 4- or 5-oxazolyl group, 3-, 4- or 5-isoxazolyl group, 2-, 4- or 5-imidazolyl group, 1,2,3- or 1,2,4-triazolyl (1,2,4-triazol-l, 3, 4 or 5-yl group, 1,2,3-triazol-l, 2 or 4-yl group), IH or 2H-tetrazolyl (lH-tetrazol-1 or 5-yl group, 2H-tetrazol-2 or 5-yl group),2-, 3- or 4-pyridyl group, 2-, 4- or 5-pyrimidyl group, 3- or 4-pyridazinyl group, quinolyl group (2-, 3-, 4-, 5-, 6-, 7- or 8-quinolyl group), isoquinolyl group (1-, 3-, 4-, 5-, 6-, 7- or 8-isoquinolyl group), indolyl group (1-, 2-, 3-, 4-, 5-, 6- or 7-indolyl group) etc.) and the like can be mentioned. The number of substitution is 1 to 6, preferably 1 to 3, more preferably 1 or 2.
Preferable examples of the "*homocyclic ring optionally having a siibstituent" formed by R^ and R* or R* and R^ together with carbon atoms bonded thereto are C3-7 cycloalkane and benzene, and more preferable examples are cyclopentane and cyclohexane.
As the "heterocyclic ring", a 5- ro 8-membered heterocyclic group containing, besides carbon atom, 1 to 4 heteroatoms selected from oxygen atom, sulfur atom, nitrogen auom and the like, and a bicyclic or tricyclic heterocyclic group condensed therewith and the like can be mentioned.

Specific examples of the heterocyclic ring include (1) a 5-manbered heterocyclic ring containing, besides carbon atom, 1 to 4 heteroatoms selected from oxygen atom, sulfur atom, nitrogen atom and the like, such as thiophene (thienyl group), furan (furyl group), pyrrole (pyrrolyl group), pyrroline (pyrrolinyl group), pyrrolidine (pyrrolidinyl group), 1,3-dioxole (1,3-dioxolyl group), oxazole (oxazolyl group), thiazole (thiazolyl group), pyrazole (pyrazolyl group), iinidazole (imidazolyl group) , imidazoline (imidazolinyl group) , isoxazole (isoxazolyl group), isothiazole (isothiazolyl group), furazan (furazanyl group), 1,2,3-thiadiazole (1,2,3-thiadiazolyl group), 1,2,5-thiadiazole (1,2,5-thiadiazolyl group), 1,2,3-triazole (1,2,3-triazolyl group), 1,2,3-triazolidine (triazolidinyl group) and the like, (2) a 6-membered heterocyclic ring containing, besides carbon atom, 1 to 4 heteroatoms selected from oxygen atom, sulfur atom, nitrogen atom and the like, such as pyridine (pyridyl group), pyrimidine (pyrimidinyl group), thiomorpholine (thiomorpholinyl group), morpholine (morpholinyl group), 1,2,3-triazine, 1,2,4-triazine (triazinyl group), piperidine (piperidinyl group), pyrane (pyranyl group), thiopyrane (thiopyranyl group), 1,4-oxazine (1,4-oxazinyl group), 1,4-dioxane (1,4-dioxanyl group), 1,4-thiazine (1,4-thiazinyl group), 1,3-thiazine (1,3-thiazinyl group), piperazine (pip>erazinyl group) , oxotriazine (oxotriazinyl group) , pyridazine (pyridazinyl group), pyrazine (pyrazinyl group) and the like can be mentioned. As the bicyclic or tricyclic condensed heterocyclic ring, a bicyclic or tricyclic condensed heterocyclic ring containing, besides carbon atom, 1 to 4 leteroatoms selected from oxygen atom, sulfur atom, nitrogen atom and the like, such as benzofuran (benzofuryl group), Denzothiazole (benzotiiiazolyl group) , benzoxazcle (benzoxazolyl group), retrazolo[1,5-b]pyridazine

(tetrazolo[l,5-b]pyridazinyl group), triazolo[4,5-b]pyridazine (txiazolo[4,5-b]pyridazinyl group), benzimidazole (benzimidazolyl group), quinoline (quinolyl group), isoquinoline (isoquinolyl group), cinnoline (cinnolinyl group), phthalazine (phtJialazinyl group), quinazoline (quinazolinyl group), quinoxaline (quinoxalinyl group), indolizine (indolizinyl group), indole (indolyl group), quinolizine (quinolizinyl group), 1,8-naphthyridine (1,8-napht±iyridinyl group), pteridine (pteridinyl group), dibenzofuran (dibenzofuranyl group), carbazole (carbazolyl group), acridine (acrydinyl group) , phenantliridine (phenantiiridinyl group) , chrbmane (chromanyl group), benzoxazine (benzoxazinyl group), phenazine (phenazinyl group) , phenothiazine (phenotliiazinyl group) , phenoxazine (phenoxazinyl group) and t±ie like can be mentioned. The parenthesis following each name of the heterocyclic ring shows a heterocyclic group corresponding to the heterocyclic ring.
As the substituent that the above-mentioned heterocyclic ring may have, for example, (1) a Ci-e alkyl group, (2) a C2-6 alkenyl group, (3) a C2-6 alkynyl group, (4) a C3-6 cycloalkyl group, (5) a cycloalkenyl group, (6) a Cy-n aralkyl group, (7) a C6-14 aryl group, (8) a Ci-e alkoxy group, (9) a C6-14 aryloxy group (e.g., phenoxy group etc.), (10) a Ci-6 alkanoyl group (e.g., formyl group, acetyl group, propionyl group, n-butyryl group, iso-butyryl group etc.), (11) a C6-14 arylearbony 1 group (e.g., benzoyl group etc.), (12) a Ci-e alkanoyloxy group (e.g., formyloxy group, acetyloxy group, propionyloxy group, n-butyryloxy group, iso-butyryloxy group etc.), (13) a Ce-n , arylcarbonyloxy group (e.g., benzoyloxy group etc.), (14) a carboxyl group, (15) a Ci-e alkoxycarbonyl group (e.g., methoxycarbonyl group, ethoxycarbonyl group, n-propoxycarbonyl group, iso-propoxycarbonyl group, n-butoxycarbonyl group, isobutoxycarbonyl group, tert-butoxycarbonyl group etc.), (16)

a carbamoyl group, (17) a N-mono-Ci-4 alkylcarbamoyl group (e.g., N-methy1carbamoyl group, N-ethylcarbamoyl group, N-propylcarbamoyl group, N-isopropylcarbamoyl group, N-butylcarbamoyl group etc.), (18) an N,N-di-Ci-4 alkylcarbamoyl group (e.g., N,N-dimethylcarbamoyl group, N,N-diethylcarbamoyl group, N,N-dipropyIcarbamoyl group, N,N-dibutylcarbamoy1 group etc.), (19) a cyclic aminocarbonyl group (e.g., 1-aziridinylcarbonyl group, 1-azetidinylcarbonyl group, 1-pyrrolizinylcarbonyl group, 1-piperidinylcarbonyl group, N-methylpiperazinylcarbonyl group, morpholinocarbonyl group etc.), (20) a halogen atom, (21) a Ci-e alkyl group optionally stxbstituted by halogen atoms (e.g. , chloromethyl group, dichloromethyl group, trifluoromethyl group, trifluoroethyl group etc.), (22) an 0x0 group, (23) an amidino group, (24) an imino group, (25) an amino group, (26) a mono- or di-Ci-4 alkylamino group (e.g., methylamino group, ethylamino group, propylamine group, isopropylamino group, butylamino group, dimethylamino group, diethylamino group, dipropylamino group, diisopropylamino group, dibutylamino group etc.), (27) a 3- to 6-membered cyclic amino group optionally containing, besides carbon atom and one nitrogen atom, 1 to 3 heteroatoms selected from oxygen atom, sulfur atom, nitrogen atom and the like (e.g., aziridinyl group, azetidinyl group, pyrrolizinyl group, pyrrolinyl group, pyrrolyl group, imidazolyl group, pyrazolyl group, imldazolidi nyl group, piperidino group, morpholino group, dihydropyridyl group, pyridyl group, N-methylpiperazinyl group, N-ethylpiperazinyl group etc.), (28) a Ci_6 alkanoylamino group (e.g. , formaraide group, acetamide group, trifluoroacetamide group, propionylamide group, butyrylamide group, isobutyrylamide group etc.), (29) a benzamide group, (30) a carbamoylamino group, (31) a N-C1-4 alkylcarbamoylamino group (e.g., N-merhylcarbamoylamino group, N-erhylcarbamoylamino group, N-propylcarbamoylamino group, N-

isopropylcarbamoylamino group, N-butylcarbamoylamino group etc.), (32) a N,N-di-Ci-4 alkylcarbamoylamino group (e.g., N,N-dimethylcarbamoylamino group, N,N-diet±iylcarbainoylainino group, N,N-dipropylcarbainoylainino group, N,N-dibutylcarbainoylainino group etc.), (33) a C1-3 alkylenedioxy group (e.g., methylenedioxy group, ethylenedioxy group etc.), (34) a -B(0H)2, (35) a hydroxy group, (36) an epoxy group (-0-), (37) a nitro group, (38) a cyano group, (39) a mercapto group, (40) a sulfo group, (41) a sulfino group, (42) a phosphono group, (43) a sulfamoyl group, (44) a Ci-e alkylsulfamoyl group (e.g., N-methylsulfamoyl group, N-ethylsulfamoyl group, N-propylsulfamoyl group, N-isopropylsulfamoyl group, N-butylsulfamoyl group etc.), (45) a di-Ci-e alkylsulfamoyl group (e.g., N,N-dimethyIsulfamoyl group, N,N-diethylsulfamoyl group, N,N-dipropylsulfamoyl group, N,N-dibutylsulfamoyl group etc.), (46) a Ci-6 alkylthio group (e.g., methylthio group, ethylthio group, propylthio group, isopropylthio group, n-butylthio group, sec-butylthio group, tert-butylthio group etc.), (47) a phenylthio group, (48) a Ci-e alkylsulfinyl group (e.g., methylsulfinyl group, ethylsulfinyl group, propylsulfinyl group, butylsulfinyl group etc.), (49) a phenylsulfinyl group, (50) a Ci-6 alkylsulfonyl group (e.g., methylsulfonyl group, ethylsulfonyl group, propylsulfonyl group, butylsulfonyl group etc.), (51) a phenylsulfonyl group and the like can be mentioned. The number of substitution is 1 to 6, preferably 1 to 3, more preferably 1 or 2.
Preferable examples of the "heterocyclic ring optionally having a substituent" formed by R^ and R* or R* and R^ together with carbon atoms bonded thereto are thiophene, furan, pyrrole, pyrroline, oxazole, thiazole, pyrazole, imidazole, imidazoline, isoxazole, isothiazole, furazan, 1,2,3-thiadiazole, 1,2,5-thiadiazole, 1,2,3-rriazole, 1,2,3-triazine, 1,2,4-triazine, 1,2,3-triazolidine, 2,2-difluoro-1,3-dioxole and 2,2,3,3-

tetrafluoro-1,4-dioxane.
In t±ie above-mentioned embodiments, the substituent of the ""homocyclic ring optionally having substituents" and the substituent of the ""heterocyclic ring optionally having substituents" are preferably selected from the group consisting of (1) Ci-g alkyl group optionally substituted by halogen atoms, (2) nitro group, (3) hydroxy group, (4) mercapto group, (5) cyano group, (6) carbamoyl group, (7) carboxyl group, (8) Ci-e alkoxycarbonyl group, (9) sulfo group, (10) halogen atom, (11) Ci-e alkoxy group, (12) Ci_6 alkylthio group, (13) Ci-e alkylsulfinyl group, (14) Ci-g alkylsulfonyl group, (15) amino group, (16) mono- or di-Ci_4 alkylamino group, (17) Ci-6 alkanoyl group and (18) Ci-e alkanoyloxy group.
The "pharmaceutically acceptable salt" may be any as long as it forms a nontoxic salt with the aforementioned compound represented by the formula (1). Examples thereof include, but are not limited to, salts with various inorganic acids such as hydrochloride, hydrobromide, hydroiodide, sulfate, nitrate, phosphate, carbonate, hydrogen carbonate, perchlorate and the like; salts with organic acids such as formate, acetate, trifluoroacetate, propionate, oxalate, glycolate, succinate, lactate, maleate, hydroxymaleate, methylmaleate, fumarate, adipate, tartrate, malate, citrate, benzoate, cinnamate, ascorbate, salicylate, 2-acetoxybenzoate, nicotinate, isonicotinate and the like; sulfonates such as methanesulfonate, ethanesulfonate, isethionate, benzenesulfonate, p-toluenesulfonate, naphthalenesulfonate and the like; salts with acidic amino acid such as aspartate, glutamate and the like; alkali metal salts such as sodium salt, potassium salt and the like; alkaline earth metal salts such as magnesium salt, calcium salt and the like; ammonium salt; salts with organic base such as rrimerhylarnine salt, rriethylamine salt, pyridine salt, picoline salt.

dicyclohexylamine salt, N,N"-dibenzylethylenediamine salt and the like; salts with amino acid such as lysin salt, arginine salt and the like; and the like. In some cases, the salt may be a water-containing product, hydrate or solvate with alcohol and the like.
In addition, the above-mentioned compound represented by the formula (1) may have various isomers. For example, E form and Z form are present as geometric isomers, and when an asymmetric carbon atom exists, enantiomer and diastereomer as stereoisomers based thereon exist, and a tautomer can exist. Accordingly, the present invention encompasses all of these isomers and mixtures thereof.
The compound of the present invention encompasses prodrug compounds and metabolites.
By the "prodrug compound" is meant a derivative of the compound of the present invention, which has a chemically or metabolically decomposable group and which, after administration to the body, restores to the original compound to show its inherent efficacy, including a complex and a salt free of covalent bond.
As the prodrug compound of the compound represented by the formula (1) of the present invention, a compound wherein the carboxyl group of the compound represented by the formula (1) is modified by ethyl group, pivaloyloxymethyl group, 1-(acetyloxy)ethyl group, 1-(ethoxycaxbonyloxy)ethyl group, 1-(cyclohexyloxycarbonyloxy)ethyl group, carboxylmethyl group, (5-methyl-2-oxo-l,3-dioxol-4-yl)methyl group, phenyl group, o-tolyl group and the like; a compound wherein the hydroxyl group of the compound represented by the formula (1) is modified by acetyl group, propionyl group, isobutyryl group, pivaloyl group, benzoyl group, 4-methylbenzoyl group, dimethylcarbamoyl group or sulfo group; a co.Tipound wherein the amino group of the compound represented by the formula (1) is

modified by hexylcarbamoyl group, 3-met±iylt±iio-l-(acetylainino)propylcarbonyl group, 1-sulfo-l-(3-ethoxy-4-hydroxyphenyl)methyl group, (5-methyl-2-oxo-l,3-dioxol-4-yl)methyl group and the like, and the like can be mentioned. Best Mode for Embodying the Invention
Now, various svibstituents and substitution sites are described in more detail in the following.
R""" is preferably a Ci-e alkyl group optionally substituted by halogen atoms, more preferably a trifluoromethyl group.
R^ is preferably a halogen atom, a Ci-e alkyl group optionally siobstituted by halogen atoms or a cyano group, more
i-
preferably a trifluoromethyl group or a cyano group.
R^ and R* are each preferably a hydrogen atoms, a halogen atom, a Ci-e alkyl group optionally substituted by halogen atoms, a Ci_6 alkoxy group optionally substituted by halogen atoms, a Ci-6 alkylthio group optionally substituted by halogen atoms or R^ and R* form a homocyclic ring together with carbon atoms Donded thereto.
R^ is preferably a hydrogen atom.
R^ is preferably a hydrogen atom or a Ci-e alkyl group, [lore preferably a hydrogen atom, a methyl group or an ethyl jroup.
n is preferably 0, 1 or 2.
Ring B and (R^)n are each preferably


wherein R^" and R^^ are as defined above.
A is preferably -N(R"") (R^) , more preferably that wherein R" is a Ci-6 alkyl group and R^ is a C4-10 cycloalkylalkyl group optionally substituted by - (CH2) r-COOR^° (wherein r and R^° are as defined above) or a Ci_6 alkyl group substituted by carboxyl group.
Preferable examples of the compound of the present invention (1) are as follows:
1. N-[3-(N"-cyclopentylmethyl-N"-ethylamino)-5,6,7,8-
tetrahydronaphthalen-2-ylmethyl]-N-[3,5-
bis(trifluoromethyl)benzyl]-(2-methyl-2H-tetrazol-5-yl)amine,
2. 3-{[N-[3-(N"-cyclopentylmethyl-N"-ethylaraino)-5,6,7,8-
tetrahydronaphthalen-2-ylmethyl]-N-(2-methyl-2H-tetrazol-5-
yl)amino]methyl}-5-trifluoromethylbenzonitrile,
3. N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-
cyclopentylmethyl-N"-etJiylamino) indan-5-ylmethyl] - (2-methyl-

2H-tetrazol-5-yl)amine,
4. N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-S-ylmethyl]-(2-methyl-2H-tetrazol-5-yl)amine hydrochloride,
5. N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-N-(2H-tetrazol-5-yl)-[3,5-bis(trifluorometiyl)benzyl]amine,
6. N- [6- {N"-cyclopentylmet±iyl-N"-et±iylamino) indan-5-ylmet±iyl]-N-[3,5-bis (trifluoromethyl)benzyl]-(pyrimidin-2-yl)amine hydrochloride,
7. N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-N-[3,5-bis(trifluoromethyl)benzyl]-(5-methyl-lH-pyrazol-3-
yl)amine,
8. 5-{N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(5-methyl-[1,2,4]oxadiazol-3-yl)amino]methyl}indan-5-yl)-N-ethylamino}pentanoic acid hydrochloride,
9. methyl trans-4-{[N-(2-{[N"-[3,5-
bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-4-trifluoromethoxyphenyl)-N-ethylamino]methyl}cyclohexanecarboxylate,
10. 3-{[N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-S-ylmethyl ]-N-(2-methyl-2H-tetraz ol-5-y1)amino]methyl}-5-trifluoromethylbenzonitrile,
11. N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-(2-ethyl-2H-tetrazol-5-yl)amine,
12. N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-(1-methyl-IH-[1,2,4]triazol-3-yl)amine,
13. 3-({N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-S-ylmethyl] -N-phenylamino}methyl)-5-trifluoromethylbenzonitrile,
14. 3-{[N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-S-ylmethyl] -N-(4,5-dimethyl-thia2ol-2-yl)amino]methyl}-S-rrifluoromethylbenzonitrile,

15. N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylinet±iyl-N"-ethylamino) ind.an-5-ylmethyl] - (t±iiazol-2-yl)amine hydrochloride,
16. 3-({N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylinethyl]-N- (thiazol-2-yl) amino}methyl) -5-
txifluorometJiylbenzonitrile hydrochloride,
17. N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmet±iyl]-(oxazol-2-yl)amine hydrochloride,
18. N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentyljnethyl-N"-ethylamino) indan-5-ylmethyl] - (5-methylthiazol-2-yl)amine hydrochloride,
19. N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-(4-methylthiazol-2-yl)amine hydrochloride,
20. N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-(4,5-dimethylthiazol-2-yl)amine hydrochloride,
21. 3-{[N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-N-(5-methylthiazol-2-yl)amino]methyl}-5-trifluoromethylbenzonitrile hydrochloride,
22. 3-{[N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-N-(4-methylthiazol-2-yl)amino]methyl}-5-
trifluoromethylbenzonitrile hydrochloride,
23. N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-(4-methyloxazol-2-yl)amine hydrochloride,
24. N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-(3-raethylisothiazol-5-yl)amine hydrochloride,
25. N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylraethyl-N"-ethylamino)indan-5-yimethyl]-(5-methylisoxazol-3-yl)amine hydrochloride,

26. N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmet±.yl-N"-ethylainino) indan-5-ylniethyl] - (3-methylisoxazol-5-yl)amine hydrochloride,
27. N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-(1-methyl-lH-pyrazol-3-yl)amine hydrochloride,
28. N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N "-etJiylaraino) indan-5-ylmet±iyl] - (1-metJtiyl-lH-pyrazol-4-yl)amine hydrochloride,
29. N-[3,5-bis (trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-(5-methyl-[1,3,4]thiadiazol-2-yl) amine hydrochloride,
30. N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-(5-methyl-[l,3,4]oxadiazol-2-yl) amine hydrochloride,
31. N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-pyridin-3-ylamine hydrochloride,
32. N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-pyridin-2-ylamine hydrochloride,
33. N-[3,5-bis(trifluoromethyl)benzyl]-N-[2-(N"-cyclopentylmethyl-N"-ethylamino) -5-trifluororaethylbenzyl]- (2-nethyl-2H-tetrazol-5-yl)amine hydrochloride,
34. 3-{[N-[2-(N"-cyclopentylmethyl-N"-ethylamino)-5-brifluoromethylbenzyl]-N-(2-methyl-2H-tetrazol-5-
(^1) amino]methyl}-5-trifluoromethylbenzonitrile hydrochloride,
35. methyl 5-[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}indan-5-yl)-N-sthylamino]pentanoate hydrochloride,
36. methyl 5-[N-(6-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-(2-methyl-2H-tetrazol-5-yl)amino]merhy1}indan-5-ylmethy1)-N-ethylamino]pentanoate hydrochloride,

37. methyl 5-[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-
(l-methyl-lH-pyrazol-3-yl)amino]methyl}indan-5-yl)-N-
ethylamino]pentanoate hydrochloride,
38. 5-[N-{6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetra2ol-5-yl) amino]methyl}indan-5-yl) -N-ethylamino]pentanoic acid hydrochloride,
39. 5-[N-(6-{[N"-{3-cyano-5-trifluoromethylbenzyl)-N"-(2-raethyl-2H-tetrazol-5-yl)amino]methyl}indan-5-yl)-N-ethylamino]pentanoic acid hydrochloride,
40. 5-[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(3-methylisoxazol-5-yl)amino]methyl}indan-5-yl)-N-ethylamino]pentanoic acid hydrochloride,
41. 5-[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(1-methyl-lH-pyrazol-3-yl) amino]methyl}indan-5-yl)-N-
ethylamino]pentanoic acid hydrochloride,
42. methyl trans-4-{[N-(3-{[N"-[3,5-
bis(trifluoromethyl)benzyl]-N"-{l-methyl-lH-pyrazol-3-yl)amino]methyl}-5,6,7,8-tetrahydronaphthalen-2-yl)-N-ethylamino]methyl}cyclohexanecarboxylate hydrochloride,
43. methyl trans-4-{[N-(3-{[N"-(3-cyano-5-
trifluoromethylbenzyl)-N"-(l-methyl-lH-pyrazol-3-
yl)amino]methyl)-5,6,7,8-tetrahydronaphthalen-2-yl)-N-
ethylamino]methyl}cyclohexanecarboxylate hydrochloride,
44. trans-4-{[N-(3-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-
(l-methyl-lH-pyrazol-3-yl) amino]methyl}-5,6,7,8-
tetrahydronaphthalen-2-yl)-N-
ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride,
45. trans-4-{[N-(3-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-
(l-methyl-lH-pyrazol-3-yl) amino]methyl}-5,6,7,8-
tetrahydronaphthalen-2-yl)-N-
ethylamino]methyljcyclohexanecarboxylic acid hydrochloride,
46. N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-
cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-(5-methyl-

[1,2,4]oxadiazol-3-yl)amine hydrochloride,
47. methyl trans-4-{[N-(6-{[N"-[3,5-
bis ItrifluoromethyDbenzyl] -N"- (l-methyl-lH-pyrazol-3-
yl)amino]methyl}indan-5-yl)-N-
ethylamino]metJiyl}cyclohexanecarboxylate hydrochloride,
48. trans-4-{[N-(6-{[N"-[3,5-bis(trifluororaethyl)benzyl]-N"-(l-methyl-lH-pyrazol-3-yl) amino]methyl}indan-5-yl)-N-ethylcimino]methyl}cyclohexanecarboxylic acid hydrochloride,
49. methyl trans-4-{[N-(6-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-(l-methyl-lH-pyrazol-3-yl)amino]methyl}indan-5-yl)-N-
ethylamino]methyl}cyclohexanecarboxylate,
50. trans-4-{ [N- (6-{ [N"- (3-cyano-5-trifluorcxnethylbenzyl) -N"-(l-methyl-lH-pyrazol-3-yl)amino]methyl}indan-5-yl)-N-ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride,
51. trans-4-{[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}indan-5-yl)-N-ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride,
52. trans-4-{[N-(6-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}indan-5-yl)^N-ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride,
53. trans-4-{[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(3-methylisoxazol-5-yl)amino]methyl}indan-5-yl)-N-ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride,
54. trans-4-{ [N-(6-{ [N"-(3-cyano-5-trifluorcsnethylbenzyl)-N"-(3-methylisoxazol-5-yl) amino]methyl}indan-5-yl)-N-ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride,
55. methyl 5-[N-(6-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-(l-methyl-lH-pyrazol-3-yl)amino]methyl}indan-5-yl)-N-
ethylamino]pentanoate hydrochloride,
56. 5-[N-(6-{[N"-(3-cyano-5-trifluorOTiethylbenzyl)-N"-(3-
methyl-isoxazol-5-yl)amino]methyl}indan-5-yl)-N-
ethylamino]pentanoic acid hydrochloride,

57. 5-[N-(6-{[N"-(3-cyano^5-trifluoromethylbenzyl)-N"-(1-methyl-lH-pyrazol-3-yl)amino]methyl}indan-5-yl)-N-ethylamino]pentanoic acid hydrochloride,
58. 5-[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(1-methyl-lH-[1,2,4]triazol-3-yl)amino]met±iyl}indan-5-yl)-N-ethylaminojpentanoic acid hydrochloride,
59. trans-4-{[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(1-methyl-lH-[1,2,4]triazol-3-yl)amino]methyl}indan-5-yl)-N-ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride,
60. trans-4-{[N-(6-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-d-methyl-lH- [1 ,2 ,4] triazol-3-yl) amino]methyl}indan-5-yl) -N-
ethylamino]methyl}cyclohexanecarboxy1ic acid,
61. N-[3,5-bis(trifluoromethy1)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-(3-methyl-[1,2,4]thiadiazol-5-yl) amine,
62. 5-[N-(6-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-(l-i\ethyl-lH- [1,2 ,4] triazol-3-yl) amino]methyl}indan-5-yl) -N-ethylamino]pentanoic acid hydrochloride,

53. methyl 5-[N-{3-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(l-methyl-lH-pyrazol-3-yl)amino]methyl}-5,6,7,8-tetrahydronaphthalen-2-yl)-N-ethylamino]pentanoate lydrochloride,
54. methyl 5-[N-(3-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-(l-methyl-lH-pyrazol-3-yl) amino]methyl}-5,6,7,8-tetrahydronaphthalen-2-yl)-N-ethylamino]pentanoate lydrochloride,
55. 5-[N- (3-{ [N"-[3,5-bis (trif luoromethyDbenzyl]-N"- (1-iethyl-lH-pyrazol-3-yl)amino]methyl}-5,6,7,8-:etrahydronaphthalen-2-yl)-N-ethylamino]pentanoic acid lydrochloride,
>6. 5-[N-(3-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-(l-aethyl-lH-pyrazol-3-yl)amino]methyl}-5,6,7,8-:etrahydronaphthalen-2-yl)-N-ethylamino]pentanoic acid

hydrochloride,
67. trans-4-{[N-(3-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-
(2-methyl-2H-tetrazol-5-yl) amino]met±iyl }-5,6,7,8-
1:etrahydronaphthalen-2-yl) -N-ethylamino]met±iyl}cyclohexanecarboxylic acid hydrochloride,
68. trans-4-{[N-(3-{[N"-(B-cyano-S-trifluororaethylbenzyl)-N"-
(2-methyl-2H-tetrazol-5-yl) amino]methyl}-5,6,7,8-
tetrahydronaphthalen-2-yl)-N-
etliylamino]methyl}cyclohexanecarboxylic acid hydrochloride,
69. trans-4-{ [N-(3-{ [N"-[3 , 5-bis (trif luoromethyDbenzyl]-N"-
(1-methyl-lH-[1,2,4]triazol-3-yl)amino]methyl}-5,6,7,8-
tetrahydronaphthalen-2-yl)-N-
ethylamino]methyl}cyclohexanecarboxylie acid hydrochloride,
70. trans-4-{[N-(3-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-
(1-methyl-lH-[1,2,4]triazol-3-y1)amino]methyl}-5,6,7,8-
tetrahydronaphthalen-2-yl)-N-
ethylamino]methyl}cyclohexanecarboxylie acid,
71. trans-4-{[N-(3-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-
(3-methylisoxazol-5-yl)amino]methyl}-5,6,7,8-
tetrahydronaphthalen"2-yl)-N-
ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride,
72. trans-4-{[N-{3-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-
(3-methylisoxazol-5-yl) amino]methyl}-5,6,7,8-
tetrahydronaphthalen-2-yl) -N-
athylamino]methyl}cyclohexanecarboxylie acid hydroch3 oride,
73. 2-(5-{N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-
:;yclopentylmethyl-N" -ethylamino) indan-5-
(^Imethyl] amino} tetrazol-2-yl) ethanol hydrochloride,
74. methyl 5-[N-(3-( [N"-[3 , 5-bis (trif luoromethyDbenzyl]-N"-(1-methyl-lH-[1,2,4]triazol-3-yl)amino]methyl}-5,6,7,8-^etrahydronaphthalen-2-y1)-N-ethylaraino]pentanoate lydrochloride,
75. methyl 5-[N-(3-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-

(1-methyl-lH-[1,2,4]triazol-3-yl)amino]methyl}-5,6,7,8-tetrahydronaphthalen-2-yl)-N-ethylamino]pentanoate hydrochloride,
76. 5-[N-(3-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(l-methyl-lH-[1,2,4]triazol-3-yl)amino]methyl}-5,6,7,8-tetrcihydronaphthalen-2-yl) -N-ethylamino]pentanoic acid hydrochloride,
77. 5-[N-(3-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-(1-methyl-lH-[1,2,4]triazol-3-yl)amino]methyl1-5,6,7,8-tetrahydronaphthalen-2-yl)-N-ethylamino]pentanoic acid hydrochloride,
78. 5-[N-(3-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(3-methylisoxazol-5-yl)amino]methyl}-5,6,7,8-tetrahydronaphthalen-2-yl)-N-ethylamino]pentanoic acid hydrochloride,
79. 5-[N-(3-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-(3-methylisoxazol-5-yl)amino]methyl}-5,6,7,8-tetrahydronaphthalen-2-yl)-N-ethylamino]pentanoic acid hydrochloride,
80. 5-[N-(3-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-5,6,7,8-tetrahydronaphthalen-2-yl)-N-ethylamino]pentanoic acid hydrochloride,
81. 5-[N-(3-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-5,6,7,8-tetrahydronaphthalen-2-yl)-N-ethylamino]pentanoic acid hydrochloride,
82. trans-4-{[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-{5-methyl-[l,2,4]oxadiazol-3-yl)amino]methyl}indan-5-yl)-N-ethylamino]methyl}cyclohexanecarboxylic acid,
83. 5-[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(1-methyl-lH-pyrazol-3-yl)amino]methyl}-4-
trifluoromethoxyphenyl)-N-ethylamino]pentanoic acid

hydrochloride,
84. 5-[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(1-methyl-lH-pyrazol-3-yl)amino]methyl}-4-trifluorometJiylphenyl)-N-ethylamino]pentanoic acid hydrochloride,
85. 5-[N-(2-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-(l-methyl-lH-pyrazol-3-yl)amino]methyl}-4-trifluoromethylphenyl)-N-ethylamino]pentanoic acid hydrochloride,
86. 5-[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-4-trifluoromethylphenyl)-N-ethylamino]pentanoic acid hydrochloride,
87. 5-[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-ethyl-2H-tetrazol-5-yl)amino]methyl}indan-5-yl)-N-ethylamino]pentanoic acid hydrochloride,
88. 5-{N-[6-({N"-[3,5-bis(trifluoromethyl)benzyl]-N"-[2-(2-hydroxyethy1)-2H-tetrazol-5-yl] amino}methyl)indan-5-yl]-N-ethylamino}pentanoic acid hydrochloride,
89. 5-[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-4-
trifluoromethoxyphenyl)-N-ethylamino]pentanoic acid hydrochloride,
90. 5-[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}indan-5-yl)-N-ethylamino]-2,2-dimethylpentanoic acid hydrochloride,
91. 6-[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}indan-5-yl)-N-ethylamino]hexanoic acid hydrochloride,
92. 5-[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-[nethyl-2H-tetrazol-5-yl) amino]methyl}indan-5-yl) -N-ethylamino]-3,3-dimethylpentanoic acid hydrochloride,
93. trans-4-{[N-{6-{[N"-[3,5-bis(rrifluoromethyl)benzyl]-N"-(2-ethyl-2H-tetrazol-5-yl) amino]met±iyl} ir.dan-5-yl) -N-ethylamino]methyl}cyclohexanecarboxylie acid hydrochloride.

94. (1-{2-[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
inethyl-2H-tetrazol-5-yl) amino]methyl}indan-5-yl) -N-
ethylamino]ethyl}cyclopentyl)acetic acid hydrochloride,
95. trans-4-({N-[6-({N"-[3,5-bis(trifluoromethyl)benzyl]-N"-
[2-(2-hydroxyethyl)-2H-tetrazol-5-yl]amino}methyl)indan-5-yl]-
N-ethylamino}methyl)cyclohexanecarboxylic acid,
96. trans-4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-
(2-methyl-2H-tetrazol-5-yl)amino]methy1}-4-
trifluoromethylphenyl)-N-
ethylamino]methyl)cyclohexanecarboxylic acid hydrochloride,
97. (l-{2-[N-(3-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
nnethyl-2H-tetrazol-5-yl) amino]methyl} -5, 6 , 7 , 8-
tetrahydronaphthalen-2-yl)-N-
ethylamino]ethyl}cyclopentyl)acetic acid,
98. trans-4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-
(2-methyl-2H-tetrazol-5-yl)amino]methy1}-4-
trifluoromethoxyphenyl)-N-
sthylamino]methyl}cyclohexanecarboxylic acid hydrochloride,
J9. trans-4-{[N-(3-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-
(2-ethyl-2H-tetrazol-5-yl)amino]methyl}-5,6,7,8-
ietrahydronaphthalen-2-yl)-N-
sthylamino]methyl}cyclohexanecarboxylic acid hydrochloride,
.00. trans-4-({N-[3-({N"-[3,5-bis(trifluoromethyl)benzyl]-N"-
.2-(2-hydroxyethyl)-2H-tetrazol-5-yl]amino}methyl)-5,6,7,8-
letrahydronaphtha1en-2-yl]-N-
ithylamino}methyl)cyclohexanecarboxylic acid hydrochloride,
.01. 1-{3-[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
iethyl-2H-tetrazol-5-yl)amino]methyl}indan-5-yl)-N-
ithylamino]propyl}cyclohexanecarboxylic acid hydrochloride,
2. 5-[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(l-iethyl-lH-pyrazol-3-yl)amino]methyl}indan-5-yl)-N-ethylamino]-i,3-dimethylpenranoic acid,
3. 5-[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(5-

met±iyl- [1,2 ,4] oxadiazol-3-yl) amino]methyl}indan-5-yl) -N-etiiylamino]-3,3-diinethylpentanoic acid hydrochloride,
104. 5-[N-{2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
methyl-2H-■tetrazol-5-yl) amino]methyl}-4-
trifluoromethoxyphenyl)-N-ethylaraino]-3,3-dimethylpentanoic acid hydrochloride,
105. 5-[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
methyl-2H-tetrazol-5-yl)amino]methy1}-4-
trifluoromethylphenyl)-N-ethylamino]-3,3-dimethylpentanoic acid hydrochloride,
106. trans-4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-
(l-methyl-lH-pyrazol-3-yl)amino]methy1}-4-
trifluoromethoxyphenyl)-N-
ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride,
107. 5-[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(l-
methyl-lH-pyrazol-3-yl)amino]methyl}-4-
trifluoromethoxyphenyl)-N-ethylamino]-3,3-dimethylpentanoic acid hydrochloride,
108. 5-iN-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(5-
methyl-[1,2,4]oxadiazol-3-yl)amino]methyl}-4-
trifluoromethoxyphenyl)-N-ethylamino]-3,3-dimethylpentanoic acid hydrochloride,
109. trans-4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-
(5-methyl-[l,2,4]oxadiazol-3-yl)amino]methyl}-4-
trifluoromethoxyphenyl)-N-
ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride,
110. 6-[N-{2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
methyl-2H-tetrazol-5-"yl) amino ] me thy 1}-4-
trifluoromethoxyphenyl)-N-ethylamino]hexanoic acid hydrochloride,
111. trans-(4-{[N-(5-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-
(2-methyl-2H-tetrazol-5-yl)aminojmethyl}indan-5-yl)-N-
ethylamino]methyl}cyclohexyl)acetic acid hydrochloride.

112. 6-[N-(6-{ [N"-[3,5-bis(trifluorome1:hyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}indan-5-yl)-N-ethylamino]-4,4-dimet±iylhexanoic acid hydrochloride, .113. 6-[N-(6-{ [N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl) amino]methyl}indan-5-yl)-N-ethylamino]-3,3-dimethylhexanoic acid hydrochloride,
114. 5-[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
methyl-2H-tetrazol-5-yl)amino]methyl}indan-5-yl)-N-
ethylamino]-4,4-dimethylpentanoic acid hydrochloride,
115. trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-
{2-methyl-2H-tetrazol-5-yl)amino]methyl}-4-
trifluoromethoxyphenyl) -N-ethylcimino] methyl }cyclohexyl) acetic acid hydrochloride,
116. 6-[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
methyl-2H-tetrazol-5-yl)amino]methy1}-4-
trifluoromethoxyphenyl)-N-ethylamino]-4,4-dimethylhexanoic acid hydrochloride,
117. 6-[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
methyl-2H-tetrazol-5-yl)amino]methy1}-4-
trifluoromethyIphenyl)-N-ethylamino]-4,4-dimethylhexanoic acid hydrochloride,
118. trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-
(2-raethyl-2H-tetrazol-5-yl)amino]methyl}-4-
trifluoromethyIphenyl)-N-ethylamino]methyl}cyclohexyl)acetic acid hydrochloride,
119. trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-
(2-methyl-2H-tetrazol-5-yl)amino]methyl}-4-
trifluoromethoxyphenyl)-N-
ethylamino]methyl}cyclohexyl)methanol hydrochloride,
120. 6-[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}indan-5-yl)-N-ethylamino]-5,5-dimethylhexanoic acid hydrochloride,
121. trans-4-{ [N- (2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-

(2-met±iyl-2H-tetrazol-5-yl) amino]methyl)-4-trifluoromethoxyphenyl)-N-propylamino]methyl}cyclohexanecarboxylic acid hydrochloride,
122. trans-4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-
(2-methyl-2H-tetrazol-5-yl)amino]methy1}-4-
trifluoromethoxyphenyl)-N-
isobutylamino]methyl}cyclohexanecarboxylic acid hydrochloride,
123. trans-4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-
(2-methyl-2H-tetrazol-5-yl)amino]methyl}-4-
trifluoromethoxyphenyl)-N-
ethylamino]methyl}cyclohexanecarboxylic acid amide, .124. trans-4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-4-trifluoromethoxyphenyl)-N-ethylamino]methyl}cyclohexanecarboxylic acid methylamide,
125. trans-4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-
(2-methyl-2H-tetrazol-5-yl)amino]methyl}-4-
trifluoromethoxyphenyl)-N-
ethylamino]methyl}cyclohexanecarboxylic acid dimethy1amide,
126. trans-4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-
(4-chlorophenyl)amino]methyl}-4-trifluoromethoxyphenyl)-N-
ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride,
127. trans-4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-
(p-tolyl) amino]methyl}-4-trifluoromethoxyphenyl)-N-
ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride,
128. trans-4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-
(m-tolyl)amino]methyl}-4-trifluoromethoxyphenyl)-N-
ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride,
129. trans-4-{[N-(2-{[N"- 130. trans-4-{ [N-erhyl-N- (2-{ [N"- (2-metiiyl-2H-tetrazol-5-yl)-N"- (3-methyl-5-rrifluoromerhylbenzyl) a.mino]methyl}-4-

trifluorometJioxyphenyl) amino]metiayl}cyclohexanecarboxylic acid hydrochloride,
131. trans-4-{[N-(2-{[N"-(3-Ghloro-5-trifluoromethylbenzyl)-
N"- (2-methyl-2H-tetrazol-5-yl)amino]methyl}-4-
trifluoromethoxyphenyl)-N-
ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride,
132. trans-4-{[N-ethyl-N-(2-{[N"-(2-methyl-2H-tetrazol-5-yl)-
N"- (3-nitro-5-trifluoromethylbenzyl) amino]methyl}-4-
trifluoromethoxyphenyl)amino]methyl}cyclohexanecarboxylic acid hydrochloride,
133. trans-(4-{[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-
(2-methyl-2H-tetrazol-5-yl)amino]methyl}-2,2-
difluorobenzo[l,3]dioxol-5-yl)-N-
ethylamino]methyl}cyclohexyl)methanol hydrochloride,
134. trans-(4-{[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-
(2-methyl-2H-tetrazol-5-yl)amino]methyl}-2,2-
difluorobenzo[1,3]dioxol-5-yl)-N-
ethylamino]methyl}cyclohexyl)acetic acid hydrochloride,
135. trans-3-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-
N"-(2-methyl-2H-tetrazol-5-yl)amino]methy1}-4-
trifluoromethoxyphenyl)-N-
e.thylamino]methyl}cyclohexyl) propionic acid hydrochloride,
136. trans-(4-{[N-(7-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-
(2-methyl-2H-tetrazol-5-yl)amino]methyl}-2,2,3,3-tetrafluoro-
2,3-d i hydrobenzo[1,4]diox i n-6-yl)-N-
ethylamino]methyl}cyclohexyl)methanol hydrochloride,
137. trans-(4-{[N-(7-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-
(2-methyl-2H-tetrazol-5-yl)amino]methyl}-2,2,3,3-tetrafluoro-
2,3-dihydrobenzo[1,4]dioxin-6-yl)-N-
ethylamino]methyl}cyclohexyl)acetic acid hydrochloride,
138. trans-2-(4-{[N-(7-{[N"-[3,5-bis(trifluoromethyl)benzyl]-
N"-{2-methyl-2H-tetrazol-5-yl)amino]methyl}-2,2,3,3-
tetrafluoro-2,3-dihydrobenzo[1,4]dioxin-6-yl)-N-

ethylamino]methyl}cyclohexy1)acetamide hydrochloride,
139. trans-N-[3,5-bis{trifluoromethyl)benzyl]-N-{2-[N"-ethyl-N"- (4- (metJioxymethyl) cyclohexyImethyl) amino] -5-trifluoromethoxybenzyl}- (2-methyl-2H-t.etrazol-5-yl) amine hydrochloride,
140. trans-2-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-4-trifluoromethoxyphenyl)-N-ethylamino]methyl}cyclohexyl)ethanol hydrochloride,
141. trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-
(2-methyl-2H-tetrazol-5-yl)amino]methyl}-4-methyl-5-
trif luoromethylphenyl) -N-ethyleimino] methyl} cyclohexyl) methanol hydrochloride,
142. trans-(4-{[N-{2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-
(2-methyl-2H-tetrazol-5-yl)amino]methyl}-5-raethyl-4-
trifluoromethylphenyl)-N-ethylamino]methyl}cyclohexyl)acetic acid hydrochloride,
143. trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-
(2-methyl-2H-tetrazol-5-yl)amino]methyl}-4-methyl-5-
trifluoromethylphenyl)-N-ethylamino]methyl}cyclohexyl)acetic acid hydrochloride,
144. trans-(4-{[N-(2"{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-
(2-methyl-2H-tetrazol-5-yl)amino]methyl}-4-
trifluoromethoxyphenyl)-N-
e thy lamino ] methyl} cyclohexy Imethyl) phosphonic acid,
145. trans-4-{[N-(2-{[N"-(3-bromo-5-trifluoromethylbenzyl)-N"-
(2-methyl-2H-tetrazol-5-yl)amino]methyl}-4-
trifluoromethoxyphenyl)-N-
ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride,
146. trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-4-bromophenyl)-N-ethylamino] methyl} cyclohexyl) metiianol hydrochloride,
147. trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-

(2-met±iyl-2H-tetrazol-5-yl)amino]methyl}-4-bromophenyl)-N-ethylamino]methyl}cyclohexyl)acetic acid hydrochloride,
148. trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-4-chloro-5-ethylphenyl)-N-ethylamino]methyl}cyclohexyl)methanol hydrochloride,
149. trans-4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(4-methoxyphenyl)amino]methyl}-4-trifluoromethoxyphenyl)-N-ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride,
150. trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-5-methoxy-4-
methylphenyl)-N-ethylamino]methyl}cyclohexyl]methanol hydrochloride,
151. trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-
(2-methyl-2H-tetrazol-5-yl)amino]methyl}-4,5-dimethylphenyl)-
N-ethylamino]methyl}cyclohexyl)acetic acid hydrochloride,
152. trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-
(2-methyl-2H-tetrazol-5-yl)amino]methy1}-4-
trifluoromethylthiophenyl)-N-
ethylamino]methyl}cyclohexyl)acetic acid hydrochloride,
153. trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-4-chloro-5-ethylphenyl)-N-ethylamino]methyl}cyclohexyl)acetic acid hydrochloride,
154. trajis-(4-{ [N-(2-{ [N"-[3,5-bis (trifluoromethyl) benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methy1}-4-
trifluoromethylphenyl)-N-propylamino]methyl}cyclohexyl)acetic acid hydrochloride,
155. trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-
(2-methyl-2H-tetrazol-5-yl)amino]methyl}-5-raethoxy-4-
nethylphenyl)-N-ethylamino]methyl}cyclohexyl)acetic acid
lydrochloride,
L56. trans-4-({N-[2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-

(2-methyl-2H-tetrazol-5-yl)amino]methyl}-4-(2,2,2-trifluoroethyl)phenyl]-N-ethylamino}methyl)cyclohexanecarboxylic acid hydrochloride,
157. trans-(4-{[N-(2-{[N"-[3,5-bis (trifluoromethyl)benzyi]-N"-
(2-methyl-2H-tet.razol-5-yl) amino]methyl}-5-methyl-4-
trifluoromethylphenyl)-N-propylamino]methyl}cyclohexyl)acetic acid hydrochloride,
158. trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethy1)benzyl]-N"-
(2-raethyl-2H-tetrazol-5-yl)amino]methyl}-4-
trifluoromethoxyphenyl)-N-propylamino]methyl}cyclohexyl)acetic acid hydrochloride,
159. trans-4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-
(4-ethylphenyl)amino]methyl}-4-trifluoromethoxyphenyl)-N-
ethylamino]methyl)cyclohexanecarboxylic acid hydrochloride,
160. trans-4-{[N-(2-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-
(2-methyl-2H-tetrazol-5-yl) amino]methyl}-4-
trifluoromethoxyphenyl)-N-
ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride,
161. trans-4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-
(4-isopropenylphenyl)amino]methyl}-4-trifluoromethoxyphenyl)-
N-ethylamino]methyl}cyclohexanecarboxylic acid, 1,62. trans-(4-{ [N-{2-{ [N"-[3 , 5-bis (trifluoromethyl) benzyl]-N"-(p-tolyl)amino]methyl}-4-trifluoromethoxyphenyl)-N-ethylamino]methyl}cyclohexyl)acetic acid dihydrochloride,
163. trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-
(5-methyl-[l,2,4]oxadiazol-3-yl)amino]methyl}-4-
trifluoromethoxyphenyl)-N-ethylamino]methyl}cyclohexyl)acetic acid hydrochloride,
164. trans-(4~{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-
(5-methyl-[1,2,4]oxadiazol-3-yl)amino]methyl}-5-methyl-4-
trifluoromethylphenyl)-N-ethylamino]methyl}cyclohexyl)acetic acid hydrochloride,
165. trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-

(5-methyl- [1,2,4] oxadiazol-3-yl) amino ] methyl} -5-met:hyl-4-trifluoromethylphenyl)-N-propylaraino]methyl}cyclohexyl)acetic acid hydrochloride,
166. trans-(4-{[N-(2-{IN"-[3,5-bis(trifluoromethyl)benzyl]-N"-
(2-methyl-2H-tetrazol-5-yl)amino]methyl}-5-methyl-4-
trifluoromethylphenyl)-N-propylamino]methyl}cyclohexyl)acetic acid,
167. trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-
(2-methyl-2H-tetrazol-5-yl)amino]methyl}-4-methyl-5-
trifluoromethylphenyl)-N-ethylamino]methyl}cyclohexyl)acetic acid,
168. trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-
(2-methyl-2H-tetrazol-5-yl)amino]methyl}-5-methyl-4-
trifluoromethylphenyl)-N-ethylamino]methyl}cyclohexyl)acetic acid methanesulfonate,
169. ethyl trans-(4-{[N-(2-{[N"-[3,5-
bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-5-methyl-4-trifluoromethylphenyl)-N-ethylamino]methyl}cyclohexyl)acetate,
170. trans-(4-{[N-(2-{[N"-[3,5-bis (trifluoromethyl)benzyl]-N"-
(2-methyl-2H-tetrazol-5-yl)amino]methyl}-5-methyl-4-
trifluoromethylphenyl)-N-ethylamino]methyl}cyclohexyl)acetic acid,
171. trans-(4-{[N-(2-{[N"-(3-methyl-5-trifluoromethylbenzyl)-
(^"- (2-methyl-2H-tetrazol-5-yl) amino]methyl}-5-methyl-4-
trifluoromethylphenyl)-N-ethylamino]raethyl}cyclohexyl)acetic
acid,
L72. trans-(4-{[N-(2-{[N"-(3-methyl-5-trifluoromethylbenzyl)-
irifluoromethylphenyl)-N-ethylamino]methyl}cyclohexyl)acetic
icid,
L73. ethyl cis-(4-{[N-(2-{[N"-[3,5-
5is(trifluoromethyl)benzyl]-N"-(2-meuhyl-2H-tetrazol-5-

yl) amino]met±iyl}-5-methyl-4-trifluoromethylphenyl) -N-etJiylamino ] met±iyl} cyclohexy 1) acetate,
174. {4-[2-(2-{[N-[3,5-bis(trifluoromethyl)benzyl]-N-(2-
methyl-2H-tetrazol-5-yl) amino]methyl}-5-methyl-4-
r
trifluoromethylphenyl)butyl]cyclohexyl}acetic acid and
175. 5-[2-({N-[3,5-bis(trifluoromethyl)benzyl]-N-[2-methyl-2H-
tetrazol-5-yl]amino}methyl)-5-methyl-4-
trifluoromethylphenoxy]heptcinoic acid.
Of the compounds recited above, the compound shown below are particularly prefereible. 115. trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-
(2-methyl-2H-tetrazol-5-yl)amino]methyl}-4-
trifluoromethoxyphenyl)-N-ethylamino]methyl}cyclohexyl)acetic acid hydrochloride, 118. trans-{4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-
(2-methyl-2H-tetrazol-5-yl)amino]methyl}-4-
trifluoromethylphenyl)-N-ethylamino]methyl}cyclohexyl)acetic acid hydrochloride,
142. trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-
(2-methyl-2H-tetrazol-5-yl)amino]methyl}-5-methyl-4-
trifluoromethylphenyl)-N-ethylamino]methyl}cyclohexyl)acetic acid hydrochloride,
143. trans-(4-{[N-(2-([N"-[3,5-bis(trifluoromethyl)benzyl]-N"-
(2-methyl-2H-tetrazol-5-yl)amino]methyl}-4-methyl-5-
trifluoromethylphenyl)-N-ethylamino]methyl}cyclohexyl)acetic acid hydrochloride,
154. trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-4-
trifluoromethylphenyl)-N-propylamino]methyl}cyclohexyl)acetic acid hydrochloride,
157. trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-raethyl-2H-tetrazol-5-yl)amino]methyl}-5-methyl-4-trifluoromethylphenyl)-N-propylamino]methyl}cyclohexyl)acetic

acid hydrochloride,
158. trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-niethyl-2H-t.,etra2ol-5-yl) amino ] me thy 1}-4-
trifluoromethoxyphenyl)-N-propylamino]methyl}cyclohexyl)acetic acid hydrochloride,
166. trans-(4-{[N-{2-{tN"-[3,5-bis(trifluoromethyl)benzyl]-N"-
(2-methyl-2H-tetrazol-5-yl) amino]methyl}-5-methyl-4-
trifluoromethylphenyl) -N-propyleimino]methyl)cyclohexyl) acetic acid,
167. trans-(4-{[N-(2-{[N"-[3,5-bis(trifluororaethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-4-methyl-5-trifluoromethylphenyl)-N-ethylamino]methyl)cyclohexyl)acetic acid and
168. trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl) amino]methyl}-5-methyl-4-brif luoromethylphenyl) -N-ethylamino]methyl)cyclohexyl)acetic acid methanesulfonate.
The compound of the present invention, a prodrug thereof md a pharmaceutically acceptable salt thereof have superior :ETP inhibitory activity in mammals (e.g., human, monkey, jovine, horse, dog, cat, rabbit, rat, mouse and the like), and ;an be used as CETP activity inhibitors. In addition, itilizing the superior CETP inhibitory activity of the :ompound of the present invention, a prodrug thereof and a )harmaceutically acceptable salt thereof, they aire useful as )harmaceutical agents effective for the prophylaxis or .reatment of the diseases in which CETP is involved (e.g., lyperlipidemia, arteriosclerosis, atherosclerosis, peripheral ascular disease, dyslipidemia, hyperbetalipoproteinemia, ypoalphalipoproteinemia, hypercholesterolemia, ypertriglyceridemia, familial hypercholesterolemia, ardiovascular disorder, angina, ischemia, heart ischemia, hrombosis, cardiac infarction, reperfusion injury.

angioplasty restenosis, hypertension, diabetic vascular complications, obesity or endotoxemia etc.), particularly as prophylactic or therapeutic agents for hyperlipidemia or arteriosclerotic diseases.
When the compound represented by the formula (1) of the present invention, a prodarug thereof or a phaimaceutically acceptcible salt thereof is used as a pharmaceutical preparation, it is generally admixed with a pharmacologically acceptable carrier, excipient, diluent, filler, disintegrant, stabilizer, preservative, buffer, eraulsifier, aromatic, coloring agent, sweetening agent, thickening agent, corrigent, dissolution aids, and other additives, which are known per se, specifically water, vegetable oil, alcohol such as ethanol and benzyl alcohol, polyethylene glycol, glycerol triacetate gelatin, carbohydrates such as lactose, starch and the like, magnesium stearate, talc, lanolin, petrolatiim and the like, and can be administered orally or parenterally in the form of tablet, pill, powder, granule, suppository, injection, eye drop, liquid, capsule, troche, aerosol, elixir, suspension, emulsion, syrup and the like.
While the dose of the pharmaceutical agent of the present invention varies depending on the kind and severity of the disease, the compound to be administered and administration route, age, sex and body weight of patients and the like, it is generally about 1-1000 mg, particularly about 50 mg-800 mg in the amount of the ccanpound represented by the formula (1) of the present invention, a prodrug thereof or a pharmaceutically acceptcible salt thereof per day for an adult by oral administration.
The pharmaceutical agent of the present invention may be administered alone or concurrently with a different prophylactic or therapeutic agent for hyperlipidemia and/or a prophylactic or therapeutic agent for arteriosclerotic

diseases, or may be used concurrently with a different pharmaceutical agent (e.g., therapeutic agent for obesity, therapeutic agent for dicibetes, therapeutic agent for hypertension, therapeutic agent for arteriosclerosis, therapeutic agent for coronary artery disease etc.). Particularly, concurrent use with a different therapeutic agent for hyperlipidemia (statin pharmaceutical agent) is expected to provide an extremely superior synergistic effect of particularly remarkable suppression of blood cholesterol.
As used herein, by "concurrent use" means a combined use of the compound of the present invention, a prodrug thereof or a pharmaceutically acceptable salt thereof with a different pharmaceutical agent, such as a therapeutic agent for hyperlipidemia, wherein the mode of use thereof is not particularly limited. For example, it includes both the administration of a pharmaceutical composition containing the compound of the present invention, a prodrug thereof or a phainnaceutically acceptable salt thereof and a different pharmaceutical agent, and the simultaneous or staggered administration of respective preparations produced separately without mixing.
While the dose of the different pharmaceutical agent to be used concurrently varies depending on the kind and severity of the disease, administration route, age, sex and body weight of patients and the like, it is generally about 1-1000 mg, particularly about 50 mg-800 mg thereof per day for an adult by oral administration.
As a therapeutic agent for hyperlipidemia to be used concurrently with the pharmaceutical agent of the present invention, statin pharmaceutical agents such as lovastatin, simvastatin, pravastatin, fluvastatin, atorvastatin, cerivastatin and the like can be menrioned.
As a therapeutic agent for obesity to be used

concurrently with the pharmaceutical agent of the present invention, raazindol and the like can be mentioned.
As a therapeutic agent for diabetes to be used concurrently with the pharmaceutical agent of the present invention, insulin preparations, sulfonylureas (e.g., glibenclamide, tolbutamide, glyclopyraraide, acetohexamide, glimepiride, tolazamide, gliclazide etc.), insulin secretagogues (e.g., nateglinide etc.), sulfonamides (e.g., glybuzole etc.), biguanides (e.g., metformin hydrochloride, bufoinnin hydrochloride etc.), a glucosidase inhibitors (e.g., voglibose, acarbose etc.), insulin sensitizers (e.g., pioglitazone hydrochloride etc.) and the like can be mentioned.
As a therapeutic agent for hypertension to be used concurrently with the pharmaceutical agent of the present invention, loop diuretics (e.g., furosemide sustained-release preparation etc.), angiotensin converting enzyme inhibitors (e.g., captopril, captopril sustained-release preparation, enalapril maleate, alacepril, delapril hydrochloride, cilazapril, lisinopril, benazepril hydrochloride, imidapril hydrochloride, temocapril hydrochloride, quinapril hydrochloride, trandrapril, perindopril erbumine etc.), angiotensin II receptor antagonists (e.g., losartan potassium, candesartan cilexetil etc.), Ca antagonists (e.g., nicardipine hydrochloride, nicardipine hydrochloride sustained-release preparation, nJLlvadipine, nifedipine, nifedipine sustained-release preparation, benidipine hydrochloride, diltiazem hydrochloride, diltiazem hydrochloride sustained-release preparation, nisoldipine, nitrendipine, manidipine hydrochloride, barnidipine hydrochloride, efonidipine hydrochloride, amlodipine besylate, felodipine, cilnidipine, aranidipine etc.), p blockers (e.g., propranolol hydrochloride, propranolol hydrochloride sustained-release preparation, pindolol, pindolol sustained-release preparation, indenolol

hydrochloride, carteolol hydrochloride, carteolol hydrochloride sustained-release preparation, bunitrolol hydrochloride, bunitrolol hydrochloride sustained-release preparation, atenolol, acebutolol hydrochloride, metoprolol tartrate, metoprolol tartrate sustained-release preparation, nipradilol, penbutolol sulfate, tilisolol hydrochloride, carvedilol, bisoprolol fumarate, betaxolol hydrochloride, celiprolol hydrochloride, bopindolol malonate, bevantolol hydrochloride etc.), a,^ blockers (e.g., labetalol hydrochloride, arotinolol hydrochloride, amosulalol hydrochloride etc.), a blockers (e.g., prazosin hydrochloride, terazosin hydrochloride, doxazosin mesylate, bunazosin hydrochloride, bunazosin hydrochloride sustained-release preparation, urapidil, phentolamine mesylate etc.) and the like can be mentioned.
Moreover, the pharmaceutical agent of the present invention can be administered not only to hiomans but also to other mammals (e.g., monkey, bovine, horse, dog, cat, rabbit, rat, mouse and the like).
Now, one embodiment of the production method of the dibenzylamino compound represented by compound (1) is explained, but the production method of the present invention is not limited to this example.
When the reaction to be mentioned below is carried out, functional groups at positions other than the reaction site may be protected beforehand as necessary and may be deprotected at a suitable stage.
Moreover, the reaction in each step may be carried out according to a conventional method, wherein isolation and purification are performed by appropriately selecting or combining conventional methods, such as crystallization, recrystallizarion, column chromatography, preparative HPLC and the like.




herein R^, R^, R^, R*, R^, R^, A, ring B and n are as defined above, X is a halogen atom and Ph is a phenyl group. Production Method 1
Step 1-1
This step is directed to a general reductive amination. The compound represented by the formula (2) is reacted with a compound represented by the formula (3) in the presence of a reducing agent in a solvent to give a compound represented by the formula (4).
As the solvent to be used for tlie reaction, for example, ether solvents such as diethyl ether, tetrahydrofuran (THF), dioxane, 1,2-dimethoxyethane, diglyrae and the like;

hydrocarbon solvents such as benzene, toluene, hexane, xylene and the like; halogenated solvents such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; alcohol solvents such as methanol, ethanol, isopropyl alcohol, tert-butanol and the like; ester solvents such as ethyl acetate, methyl acetate, butyl acetate and the like; polar solvents such as acetic acid, N,N-dimethylformamide and the like; and the like can be mentioned, which can be used alone or in combination. Preferable solvents in this reaction are chloroform and dichloromethane.
As the reducing agent, sodium triacetoxyborohydride, sodiiam cyanoborohydride, sodium borohydride and the like can be mentioned. A preferable reducing agent in this reaction is sodium triacetoxyborohydride. Step 1-2
This step is directed to a general alkylation. A compound represented by the formula (4) is reacted with a compound represented by the formula (5) in a solvent in the presence of a base to give one of the object compounds, which is represented by the formula (1-a) .
As the solvent to be used for the reaction, for example, ether solvents such as diethyl ether, tetrahydrofuran (THF), dioxane, 1,2-dimethoxyethane, diglyme and the like; hydrocarbon solvents such as benzene, toluene, hexane, xylene and the like; alcohol solvents such as methanol, ethanol, isopropyl alcohol, tert-butanol and the like; ester solvents such as ethyl acetate, methyl acetate, butyl acetate and the like; polar solvents such as acetone, N,N-dimethylformamide, dimethyl sulfoxide and the like; and the like can be mentioned, which can be used alone or in combination. A preferable solvent in this reaction is N,N-dimethylformamide.
As the base, for example, alkali metal hydrides (e.g., sodium hydride, potassium hydride etc.); alkali metal

alkoxides (e.g., sodium ethoxide, sodium methoxide, potassium tert-butoxide etc.); alkyllithiums (e.g., n-butyllithium, sec-butyllithium etc.); alkali metal amides (e.g., lithiiom diisopropylamide, sodiiom amide, lithium bistrimethylsilylamide etc.); alkali metal carbonates (e.g., sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassi\am hydrogen carbonate etc.); alkali metal hydroxides (e.g., lithium hydroxide, sodium hydroxide, potassiiom hydroxide etc.); alkali metal phosphates (e.g., sodium phosphate, potassium phosphate etc.); and organic bases (e.g., triethylamine, pyridine, N-methylmorpholine etc.) can be mentioned, with preference given to sodium hydride and potassium tert-butoxide.
The obtained object compound may be subjected to a salt-forming reaction to give a desired salt. Production Method 2 Step 2-1
This step is directed to a general reductive amination. A compound represented by the formula (6) is reacted with a compound represented by the formula (3) in a solvent in the presence of a reducing agent to give a compound represented by the formula (7) .
As the solvent, for example, ether solvents such as diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane, diglyme and the like; hydrocarbon solvents such as benzene, toluene, hexane, xylene and the like; halogenated solvents such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; alcohol solvents such as methanol, ethanol, isopropyl alcohol, tert-butanol and the like; ester solvents such as ethyl acetate, methyl acetate, butyl acetate and the like; polar solvents such as N,N-dimethylformamide and the like; and the like can be mentioned, which can be used alone or in combination. Preferable solvents

in this reaction are dichloromethane and toluene.
As the reducing agent, sodium triacetoxyborohydride, sodium cyanoborohydride, sodium borohydride, lithium hydride, aluminum hydride and the like can be mentioned. A preferable reducing agent in this reaction is sodium borohydride.
As a different method, the formula (6) is reacted with the formula (3) to once give a Schiff base, which is followed by a reduction. For a reaction to form a Schiff base, azeotropic dehydration may be conducted in a solvent such as benzene, toluene, ethanol and the like without catalyst or in the presence of an acid catalyst such as hydrochloric acid, acetic acid and the like, or a method using a dehydrating agent such as molecular sieves and the like in an aprotic solvent such as methylene chloride, toluene and the like may be employed. Step 2-2
A compound represented by the formula (8), which is obtained by treating the formula (2) by a general reduction, is reacted with thionyl chloride in a solvent such as toluene, tetrahydrofuran, chloroform and the like to give a compound wherein hydroxyl group of the formula (8) is chlorinated. Next, a similar reaction as in Step 1-2 using the obtained compound and a compound represented by the formula (7) gives one of the object compounds, which is represented by the formula (1-a). Production Method 3 Step 3-1
This step is directed to a general reductive amination. h compound represented by the formula (2) is reacted with a compound represented by the formula (9) in a solvent in the presence of a reducing agent to give a compound represented by the formula (10).
As the solvent, for example, ether solvents such as diethyl ether, retrahydrofuran, dioxane, 1,2-dimethoxyethane,

diglyine and the like; hydrocarbon solvents such as benzene, toluene, hexane, xylene and the like; halogenated solvents such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; alcohol solvents such as methanol, ethanol, isopropyl alcohol, tert-butanol and the like; ester solvents such as ethyl acetate, methyl acetate, butyl acetate and the like; polar solvents such as NjN-dimethylformamide and the like; and the like can be mentioned, which can be used alone or in combination. A preferable solvent in this reaction is dichloromethane.
As the reducing agent, sodium triacetoxyborohydride, sodium cyanoborohydride, sodium borohydride and the like can be mentioned. A preferable reducing agent in this reaction is sodium triacetoxyborohydride. Step 3-2
This step is directed to a general nucleophilic substitution reaction. In a similar manner as in Step 1-2, a compound represented by the formula (10) is reacted with a compound represented by the formula (11) to give one of the object compounds, which is represented by the formula (1-a).
Besides such method comprising directly reacting a compound having ring B, which is represented by the formula (11), there is a method comprising forming ring B on the nitrogen atom of compound (10) by a known method. As an exan^ile of this method, the following production method 3" and production method 3" are shown.

Step 3"-l
A compound represenred bv rhe formula (10) is reacted

witJi compound (12) in a solvent. The obtained residue is reacted with hydrazine hydrate in a solvent in the presence of an acid to give a compound represented by the formula (1-b), which is one of the object compounds.
As the solvent to be used for the first reaction, for example, ether solvents such as diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane, diglyme and the like; hydrocarbon solvents such as benzene, toluene, hexane, xylene and the like; halogenated solvents such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; ester solvents such as ethyl acetate, methyl acetate, butyl acetate and the like; polar solvents such as N,N-dimethylformaraide and the like; and the like can be mentioned, which can be used alone or in combination. A preferable solvent in this reaction is dichloromethane.
As the solvent to be used for the next reaction, for example, ether solvents such as diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane, diglyme and the like; hydrocarbon solvents such as benzene, toluene, hexane, xylene and the like; halogenated solvents such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; alcohol solvents such as methanol, ethanol, isopropyl alcohol, tert-butanol and the like; ester solvents such as athyl acetate, methyl acetate, butyl acetate and the like; polar solvents such as N,N-dimethylformamide, dimethyl sulfoxide and the like; and the like can be mentioned, which :an be used alone or in combination. A preferable solvent in ihis reaction is 1,2-dimethoxyethane.
As the acid to be used for the reaction, for example. Inorganic acids such as hydrochloric acid, sulfuric acid, litric acid and the like; organic acids such as :rifluoroacetic acid, trichloroacetic acid, acetic acid, [lethanesulfonic acid, p-toluenesulfonic acid and the like; and

a mixture thereof can be mentioned, with preference given to methanesulfonic acid. Production Method 3"

Step 3"-!
A compound represented by the formula (10) is reacted with cyanogen bromide in a solvent in the presence of a base, and the obtained residue is reacted with hydroxylamine in a solvent. The obtained residue is reacted with an acylating agent, such as acid chloride represented by the formula (13) and the like, in a solvent to give a compound represented by the formula (1-c), which is one of the object compounds.
As the solvent to be used for the first reaction, for example, alcohol solvents such as methcinol, ethanol, isopropyl alcohol, tert-butanol and the like; ether solvents such as diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane, diglyme and the like; hydrocarbon solvents such as benzene, toluene, hexane, xylene and the like; halogenated solvents such as dichlororaethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; ester solvents such as ethyl acetate, methyl acetate, butyl acetate and the like; polar solvents such as N,N-d±methylformamide and the like; and the like can be mentioned, which can be used alone or in combination. A preferable solvent in this reaction is methanol.
As the base to be used for the first reaction, for example, alkali metal carbonates (e.g., sodium carbonate, potassiijm carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate etc.); alkali metal phosphates (e.g., sodium phosphate, potassium phosphate etc.); and organic bases (e.g., trierhylamine, pyridine, N-methylmorpholine etc.) can

be mentioned, witii preference given to sodium hydrogen carbonate.
As the solvent to be used for the next reaction, for example, ether solvents such as diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane, diglyme and the like; hydrocarbon solvents such as benzene, toluene, hexane, xylene and the like; halogenated solvents such as dichlororaethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; alcohol solvents such as methanol, ethanol, isopropyl alcohol, tert-butanol and the like; polar solvents such as N,N-dimethylformamide, dimethyl sulfoxide and the like; and the like can be mentioned, which can be used alone or in combination. A prefercible solvent in this reaction is dioxane.
As the solvent to be used for the final reaction, for example, ether solvents such as diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane, diglyme and the like; hydrocarbon solvents such as benzene, toluene, hexane, xylene and the like; halogenated solvents such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; ester solvents such as ethyl acetate, methyl acetate, butyl acetate and the like; polar solvents such as N,N-dimethylformamide, dimethyl sulfoxide and the like; and the like can be mentioned, which can be used alone or in combination. A preferable solvent in this reaction is pyridine.
In addition. A, B and R^ to R^ may be further subjected to conversion of a functional group according to a known nethod, after synthesis of compound (1) in the above-mentioned production method.
As a functional group conversion reaction, for example, (fhen the terminal of substituent A is an ester, the obtained compound (1-a) is subjected to a conventional ester hydrolysis, thereby a compound having a carboxyl group as the terminal of substituent A can be easily obtained. As the solvent to be

used for this ester hydrolysis reaction, for example, ether solvents such as diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane, diglyme and the like; alcohol solvents such as methanol, ethanol, isopropyl alcohol, tert-butanol and the like, and water can be mentioned, which may be used alone or in combination. Similarly, as the base to be used for this ester hydrolysis reaction, metal hydroxides such as sodium hydroxide, potassium hydroxide, lithium hydroxide and the like, and the like can be mentioned.
In addition, a method exists which comprises, after deprotection of protected hydroxyl group at the terminal of substituent A, conversion to cyano group, carboxyl group and the like.
A compound represented by the formula (2), which is a starting material of the above-mentioned production method, can be produced according to a conventionally known method. In the following, some examples thereof are explained. Production Method 4

wherein R^, R*, R^ and R" are as defined above, and -CHaR^* is a group corresponding to the aforementioned R^.
Aniline represented by the formula (15) is reacted with an acid halide and the like in the presence or absence of a oase under cooling to heating in an organic solvent, water, or

without solvent, whereby a compound represenred by the formula (16) can be synthesized (Step 4-1). The compound represented by the formula (16) is reacted with a reducing agent such as lithium aluminiom hydride, Red-Al, sodium borohydride and the like under cooling to heating in an organic solvent, whereby a compound represented by the forimila (17) can be synthesized (Step 4-2) . The compound represented by the formula (17) is reacted with alkyl halide and the like in the presence or absence, of a base under cooling to heating in an organic solvent or water, or without solvent, whereby a compound represented by the formula (18) can be synthesized (Step 4-3). The compound represented by the formula (18) is reacted using a Vilsmeier reagent prepared from phosphorus oxychloride and N,N-diraethylformamide and the like under cooling to heating in an organic solvent or without solvent, whereby a compound represented by the formula (2-a), which is one of the desired starting materials, can be synthesized (Step 4-4). Production Method 5

wherein R^, R*, R^, R"^, R" and R" are as defined above.
Phenol represented by the formula (19) is reacted with alcohol represented by the formula; (R") (R") (R")COH (wherein R^^, R^^ and R^^ are as defined above) in the presence of triphenylphosphine using a condensing agent such as diethyl azodicarboxylate and the like under cooling to heating in an organic solvent or water, or without solvent, whereby a compound represented by rhe formula (20) can be synthesized (Step 5-1). The compound represented by the formula (20) is

reacted using a Vilsmeier reagent prepared from phosphoirus oxychloride and N,N-dimethylfonnamide and the like under cooling to heating in an organic solvent or without solvent, whereby a compound represented by the formula (2-b), which is one of the desired starting materials, can be synthesized (Step 5-2).

wherein R^, R*, R^, R^^ and R"^^ are as defined above, and X is a halogen atom.
Halobenzene represented by the formula (21) and butyllithium are reacted in an organic solvent under cooling to room temperature and a lithio form generated is treated with ketone, aldehyde and the like, whereby a compound represented by the formula (22) can be synthesized (Step 6-1). The conqDound represented by the formula (22) is hydrogenated in the presence of a catalyst such as palladium hydroxide and the like at room temperature or under heating in an organic solvent or water, whereby a compound represented by the formula (23) can be synthesized (Step 6-2). The compound represented by the formula (23) is reacted using a brominating agent such as bromosuccinimide and the like under cooling to heating in an organic solvent or without solvent, whereby a compound represented by rhe formula (24) can be synthesized

(Step 6-3) . The compound represented by the formula (24) and butyllithium are reacted in an organic solvent under cooling to room temperature and a lithio form generated is treated with N,N-dimethylformamide and the like, whereby a compound represented by the formula (2-c), which is one of the desired starting materials, can be synthesized (Step 6-4).

wherein R^, R*, R^, R" and R^ are as defined above.
A fluorobenzene compound represented by the formula (25) and LDA, butyllithium and the like are reacted in an organic solvent under cooling to room temperature and a lithio form generated is treated with N,N-dimethylfo3::mamide and the like, whereby a compound represented by the formula (26) can be synthesized (Step 7-1). The compound represented by the formula (26) is reacted with an amine represented by the formula; (R?) (R8)NH in the presence of a base such as potassium carbonate and the like under cooling to heating in an organic solvent or without solvent, whereby a confound represented by the formula (2-d), which is one of the desired starting materials, can be synthesized (Step 7-2).
The present invention is explained in more detail in the following by referring to Examples, which are not to be construed as limitative.
Examples Example 1 N-[3-(N"-cyclopentylmethyl-N"-ethylamino)-5,6,7,8-

tetrahydronaphthalen-2-ylmethyl]-N-[3,5-
bis(trifluoromet±iyl)benzyl]-(2-methyl-2H-tetrazol-5-yl) amine a) N-[3-(N"-cyclopentylmethyl-N"-ethylamino)-5,6,7,8-tetrahydronaphthalen-2-ylmethyl]-(2-methyl-2H-tetrazol-5-yl)amine
To a solution (10 ml) of 3-(N-cyclopentylmet±lyl-N-ethylamino) -5,6,7,8-tetrahydronaphthalene-2-carbaldehyde (333 mg) and 5-amino-2-methyltet,razole (231 mg) in chloroform was added sodium triacetoxyborohydride (745 mg) with stirring at room temperature, and acetic acid (13 jil) was added successively. The reaction solution was stirred overnight.and sodium borohydride (50 mg) and methanol (3 ml) were added. The mixture was further stirred for 2 hr. The reaction solution was washed successively with saturated aqueous sodium hydrogen carbonate, water and saturated brine, and the organic layer was dried over sodium sulfate. Sodium sulfate was filtered off and the filtrate was concentrated. The obtained residue was purified by coliomn chromatography (n-hexane: ethyl acetate=6:1 -^3:1) to give the title compound (254 mg, 59%). ^HNMR(CDCl3, 400MHz)5: 1.01(t, J=7. IHz, 3H) , 1.10-1.30(m, 2H) , L.30-1.62(m, 4H), 1.67-1.82(m, 6H), 1.93-2.10(m, IH), 2.63-2.77(m, 4H), 2.81(d, J=7.1Hz, 2H), 2.94(q, J=7.1Hz, 2H), 1.14(s, 3H), 4.51(d, J=5.8Hz, 2H), 5.35-5.50 (brs, IH), 6.87(s, LH) , 7.03(s, IH) .
3) N-[3-(N"-cyclopentylmethyl-N"-ethylamino)-5,6,7,8-:etrahydronaphthalen-2-ylmethyl]-N-[3,5-)is(trifluoromethyl)benzyl]-(2-methyl-2H-tetrazol-5-yl)amine
To a solution (2 ml) of N-[3-(N"-cyclopentylmethyl-N"-ithylamino) -5,6,7,8-tetrahydronaphthalen-2-ylmethyl]-(2-iethyl-2H-tetrazol-5-yl)amine (121 mg) obtained in Example 1 .) in N,N-dimethylformamide (DMF) was added sodium hydride (16 ig) with stirring at room temperature. The reaction solution "as stirred for 1 hr and 3,5-bis(trifluoromethyl)benzyl

bromide (73 jj,l) was added. The mixture was further stirred overnight. Water was added to the reaction solution and the mixture was extracted with ethyl acetate. The extract was washed successively with water and saturated brine and the organic layer was dried over sodium sulfate. Sodium sulfate was filtered off and the filtrate was concentrated. The obtained residue was purified by column chromatography (n-hexane:ethyl acetate=10:1) to give the title compound (102 mg, 52%) (see Table 1). Example 2
3-{[N-[3-(N"-cyclopentylmethyl-N"-ethylamino)-5,6,7,8-tetrahydronaphthalen-2-ylmethyl]-N-(2-methyl-2H-tetrazol-5-yl) amino]methyl}-5-trifluoromethylbenzonitrile
a) 3-bromomethyl-5-trifluororaethylbenzonitrile
To a solution (10 ml) of 3-hydroxymethyl-5-trifluoromethylbenzonitrile (1.00 g) and carbon tetraisromide (1.81 g) in dichloromethane was added triphenylphosphine (1.37 g) with stirring under ice-cooling, and the mixture was continuously stirred for 30 min. The reaction solution was concentrated and the obtained residue was purified by column chromatography (n-hexane:ethyl acetate=9:l) to give the title compound (1.11 g, 84%). ^HNMR(CDCl3, 400MHz)5: 4.50(s, 2H) , 7.85(s, IH) , 7.87(s, 2H) .
b) 3-{[N-[3-(N"-cyclopentylmethyl-N"-ethylamino)-5,6,7,8-
tetrahydronaphthalen-2-ylmethyl]-N-(2-methyl-2H-tetrazol-5-
yl)amino]methyl}-5-trifluoromethylbehzonitrile
To a solution (2 ml) of N-[3-(N"-cyclopentylmethyl-N"-ethylamino)-5,6,7,8-tetrahydronaphthalen-2-ylmethyl]-(2-Tiethyl-2H-tetrazol-5-yl) amine (132 mg) obtained in Example 1 a) in DMF was added sodium hydride (17 mg) with stirring at room temperature. The reaction solution was stirred for 1 hr and 3-bromomethyl-5-trifluororaethylbenzonitrile (114 mg) obtained in Example 2 b) was added. The mixture was further

stirred overnight.
Water was added to the reaction solution and the mixture was extracted with ethyl acetate. The extract was washed successively with water and saturated brine and the organic layer was dried over sodium sulfate. Sodium sulfate was filtered off and the filtrate was concentrated. The obtained residue was purified by column chromatography (n-hexane:ethyl acetate=6:l) to give the title compound (86 mg, 44%) (see Table 1). Example 3
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-(2-methyl-2H-tetrazol-5-yl) cimine
In a similar manner as in Example 1, the title compound was obtained (see Table 1). Example 4
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-(2-methyl-2H-tetrazol-5-yl)amine hydrochloride
To a solution (12 ml) of N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-(2-methyl-2H-tetrazol-5-yl)amine (550 mg) obtained in Example 3 in n-hexane was added dropwise IN hydrochloric acid-diethyl ether (0.76 ml) with stirring at room temperature. The precipitated solid was collected by filtration and dried to give the title compound (332 mg) (see Table 1). Exanple 5
N-[6-(N"-cyclopentylmethy1-N"-ethylamino)indan-5-yImethy1]-N-(2H-tetrazol-5-yl)-[3,5-bis(trifluoromethyl)benzyl]amine
To a solution (1 ml) of a compound obtained in a similar manner as in Example 1, N-[6-(N"-cyclopentylmethyl-N"-ethylamino) indan-5-ylmerhyl]-N-[3,5-

bis(trifluoromethyl)benzyl]-(2-triphenylmethyl-2H-tetrazol-5-yl) amine (75 mg) , in et±iyl acetate was added dropwise 4N hydrochloric acid-ethyl acetate (3 ml) with stirring at room temperature. The mixture was stirred at room temperature for 1.5 hr and IN aqueous sodium hydroxide, then aqueous citric
acid solution were added. The mixture was extracted with ethyl
*
acetate and the extract was washed successively with water and saturated brine. The organic layer was dried over sodium sulfate. Sodium sulfate was filtered off and the filtrate was concentrated. The obtained residue was purified using a preparative TLC plate (n-hexane:ethyl acetate=2:1) to give the title compound (24 mg, 46%) (see Table 1). Example 6
N-[6-(N"-cyclopentyLmethyl-N"-ethylamino)indan-5-ylmethyl]-N-[3,5-bis(trifluoromethyl)benzyl]-(pyrimidin-2-yl) amine hydrochloride
a) N-cyclopentylmethyl-N-{6-[[3,5-bis(trifluoromethyl)benzylamino]methyl]indan-5-yl}-ethylamine
To a solution (20 ml) of 6-(N-cyclopentylmethyl-N-ethylamino) indane-5-carbaldehyde (1.09 g) and 3,5-bis(trifluoromethyl)benzylamine (1.26 g) in dichloromethane was added sodium triacetoxyborohydride (1.70 g) with stirring at room temperature. The reaction solution was stirred overnight. The reaction solution was washed successively with satiirated aqueous sodium hydrogen carbonate, water and saturated brine, and the organic layer was dried over sodium sulfate. Sodiiam sulfate was filtered off and the filtrate was concentrated. The obtained residue was purified by coliomn chromatography (n-hexane:ethyl acetate=6:l) to give the title compound (1.65 g, 83%).
^HNMR(CDCl3, 300MHz)5: 0.95(t, J=7.1Hz, 3H), 1.04-1.22(m, 2H), 1.35-1.78(m, 6H), 1.90-2.17 (m, 3H), 2.78(d, J=7.4Hz, 2H), 2.75-2.95(m, 6H) , 3.84(s, 2H) , 3.88(s, 2H) , 7.07{s, IH) ,

7.12(s, IH) , 7.75(s,lH), 7.83(s, 2H) .
b) N-[6-(N"-cyclopentylmethyl-N"-ethylamino) indan-5-ylinethyl]-
N-[3,5-bis(trifluoromethyl)benzyl]-{pyrimidin-2-yl)amine
To a solution (3 ml) of N-cyclopentylmethyl-N-{6-[[3,5-bis(trifluoromethyl)benzylamino]methyl]indan-5-yl}-ethylamine (150 mg) obtained in Exan^sle 6 a) and 2-chloropyrimidine (69 mg) in toluene was added triethylamine (0.17 ml) with stirring at room ten5)erature. The reaction solution was refluxed with stirring overnight and concentrated. The obtained residue was purified using a preparative TLC plate (n-hexane:ethyl acetate=6:l) to give the title compound (68 mg, 39%). ^HNMR(CDCl3, 400MHz)5: 0.92(t, J=7.1Hz, 3H), 0.97-1.12(m, 2H), 1.30-1.60(m, 6H) , 1.83-2.08(m, 3H) , 2.80-2.93(m, 8H), 4.86{s, 2H) , 5.06(s, 2H) , 6.59(t, J=4.7Hz, IH) , 6.91(s, IH) , 7.04{s, IH) , 7.66(s, 2H) , 7.71(s, IH) , 8.36(d,J=4.7Hz,2H) .
c) N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-
N-[3,5-bis(trifluoromethyl)benzyl]-(pyrimidin-2-yl)amine
hydrochloride
In a similar manner as in Example 4, the title compound (50 mg) was obtained from N-[6-(N"-cyclopentylmethyl-N"-ethylamino) indan-5-ylmethyl]-N-[ 3,5-
bis(trifluoromethyl)benzyl]-(pyrimidin-2-yl)amine (68 mg) obtained in Example 6 b) (see Table 2). Exanple 7
N-[6-(N"-cyclopentylmethyl-N"-ethylami no)indan-5-ylmethyl]-N-[3,5-bis(trifluoromethyl)benzyl]-(5-methyl-lH-pyrazol-3-yl) amine
To a solution (20 ml) of N-cyclopentylmethyl-N-{6-[[3,5-bis(trifluoromethyl)benzylamino]methyl]indan-5-yl}-ethylamine (500 mg) obtained in Example 6 a) in dichloromethane was added liketene (85 p.!) with sT.irring under ice-cooling. The reaction solution was stirred for 2 hr. The reaction solution was concentrated and a parr (250 mg) of the obtained residue was

dissolved in dimethoxyet±iane (0.7 ml) and methanestilfonic acid (0.56 ml) and then hydrazine hydrate (0.21 ml) were added dropwise with stirring under ice-cooling. The reaction solution was stirred at room temperature for 5 days and saturated aqueous sodiuim hydrogen carbonate was added. The mixture was extracted with ethyl acetate and washed successively with water and saturated brine. The organic layer was dried over sodium sulfate. Sodium sulfate was filtered off and the filtrate was concentrated. The obtained residue was purified using a preparative thin layer chromatography (TLC) plate (n-hexane:ethyl acetate=4:l) to give the title compound (58 mg) (see Table 2). Example 8
5-(N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(5-methyl-[l,2,4]oxadiazol-3-yl)amino]methyl}indan-5-yl)-N-ethylamino}pentanoic acid hydrochloride
a) methyl 5-[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(5-methyl-[l,2,4]oxadiazol-3-yl)amino]methyl}indan-5-yl)-N-ethylamino]pentanoate
To a suspension (10 ml) of methyl 5-(N-{6-[N"-(3,5-bis(trifluoromethyl)benzylamino)methyl]indan-5-yl}-N-ethylamino)pentanoate (500 mg) obtained in a similar manner as in Example 6 a) and sodium hydrogen carbonate (160 mg) in methanol was added cyanogen bromide (165 mg) with stirring at room temperature and the stirring was continued for 2 hr.
The reaction solution was diluted with ethyl acetate and washed successively with water and saturated brine. The organic layer was dried over sodium sulfate. Sodium sulfate was filtered off and the filtrated was concentrated. The obtained residue was dissolved in 1,4-dioxane (5 ml). Thereto was added aqueous hydroxylamine solution (50%, 0.14 ml) and the mixture was stirred at room temperature for 5 hr. The reaction solution was concentrated and the obtained residue

was dissolved in pyridine (10 ml). Acetyl chloride (0.1 ml) was added with stirring under ice-cooling. The stirring was continued at room temperature for 30 min, and at 13(>°C for 3 hr. The reaction solution was concentrated and the obtained residue was purified by column chromatography (n-hexane:ethyl acetate=4:l) to give the title compound (178 mg, 31%). ^HNMR(CDCl3, 300MHz) 5: 0.88(t, J=7. OHz, 3H) , 1.25-1.60 (m, 4H) , L.95-2.10(m, 2H), 2.20(t, J=7.3Hz, 2H) , 2.49 (s, 3H) , 2.70-?.90(m, 8H) , 4.56(s, 2H) , 4.72(s, 2H) , 6.99(s, IH) , 7.02(s, LH) , 7.65(s, 2H) , 7.72{s, IH) .
3) 5-{N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(5-methyl-[l,2,4]oxadiazol-3-yl) amino]methyl}indan-5-yl)-N-jthylamino}pentanoic acid hydrochloride
To a solution (5 ml) of methyl 5-[N-(6-{[N"-[3,5-)is(trifluoromethyl)benzyl]-N"-{5-methyl-[1,2,4]oxadiazol-3-"^l) amino]methyl}indan-5-yl)-N-ethylamino]pentanoate (178 mg) )btained in Example 8a) in tetrahydrofuran-methanol (THF-MeOH ::1) was added aqueous sodium hydroxide solution (4N, 2 ml) rith stirring at room temperature. The reaction solution was itirred overnight and water was added. The mixture was :xtracted with ethyl acetate and the extract was washed uccessively with water and saturated brine. The organic layer as dried over sodium sulfate and sodium sulfate was filtered ff. The filtrate was concentrated and the obtained residue as purified by column chromatography (n-hexane:ethyl cetate=2:l). To a solution (7 ml) of the obtained compound in -hexane was added dropwise IN hydrochloric acid-diethyl ether 0.3 ml) with stirring at room temperature. The precipitated olid was collected by filtration and dried to give the title ompound (158 mg, 86%) (see Table 2). xample 9
ethyl ■crans-4-{ [N- (2-{ [N"-[3,5-bis (trif luoromethyl) benzyl]-"- (2-merhyl-2H-tetra2ol-5-yl)amino]methyl}-4-

trifluoromethoxyphenyl)-N-
ethylamino]methyl}cyclohexanecarboxylate
a) 5-{[3,5-bis(trifluoromethyl)benzyl]amino}-2-methyl-2H-
:etrazole
A solution (70 ml) of 3,5-)is (trifluorcMnethyl)benzaldehyde (6.71 g) and 5-amino-2-lethyltetrazole (3.30 g) in toluene was heated under reflux :or 4 hr. The reaction solution was concentrated and the )btained residue was dissolved in ethanol (70 ml), and sodium )orohydride (2.10 g) was added with stirring at room :emperature. The reaction solution was stirred at room lemperature for 30 min, and saturated aqueous ammonium ihloride was added. The mixture was extracted with ethyl icetate. The extract was washed successively with water and saturated brine. The organic layer was dried over sodium iUlfate and sodium sulfate was filtered off. The filtrate was :oncentrated and the obtained residue was recrystallized from sopropanol - water (3:7, 50 ml) to give the title compound. HNMR(CDCl3,300MHz) 6: 4.16(s,3H), 4 . 66 (d, J=6 . 3Hz2H) , .92(brs,lH), 7.79(s,lH), 7.83(s,2H). ) methyl trans-4-{[N-(2-{[N"-[3,5-
is(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-1)amino]methyl}-4-trifluoromethoxyphenyl)-N-thylamino]methyl}cyclohexanecarboxylate
To a solution (5 ml) of methyl trans-4-{[N-ethyl-N-(2-ydroxyraethy1-4-
rifluoromethoxyphenyl) amino]methyl}cyclohexylcarboxylate (330 g) in chloroform was added thionyl chloride (0.074 ml) with tirring under ice-cooling, and the stirring was continued for 0 min. The reaction solution was treated with aqueous sodium ydrogen carbonate, extracted with ethyl acetate and washed uccessively with water and saturated brine. The organic layer as dried over sodium sulfate and sodium sulfate was filtered

off. The filtrate was concentrated and the obtained residue was dissolved in DMF (3 ml). This solution was added dropwise to a solution (3 ml) of 5-[[3,5-
bis(trifluoromethyl)benzyl]amino]-2-methyl-2H-tetrazole (331 mg) obtained in Example 9 a) and sodium hydride (51 mg) in DMF with stirring at room temperature. The stirring was continued for 15 min and saturated aqueous ammonium chloride was added. The mixture was extracted with ethyl acetate. The extract was washed successively with water and saturated brine. The organic layer was dried over sodium sulfate and sodium sulfate was filtered off. The filtrate was concentrated and the obtained residue was purified by column chromatography (n-hexane:ethyl acetate=4:l) to give the title compound (366 mg, 62%) (see Table 2). Example 169
ethyl trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-5-methyl-4-trifluoromethylphenyl)-N-ethylamino]methyl}cyclohexyl)acetate a) 2-fluoro-4-methyl-5-trifluoromethylbenzaldehyde
To a suspension (200 ml) of 5-fluoro-2-iodotoluene (110.6 g) and copper iodide (76.2 g) in N-methylmorpholine was added dropwise methyl fluorosulfonyl(difluoro)acetate (150 g) with stirring at 120°C over 2 hr. The stirring was continued at the same temperature for 3.5 hr and the reaction solution was distilled under atmospheric pressure to give a yellow liquid. This was diluted with hexane (300 ml) and washed with saturated brine. The organic layer was dried over sodium sulfate and sodium sulfate was filtered off. The obtained tiexane solution was added dropwise over 1.5 hr to a mixture of tetrahydrofuran (300 ml) and 1.0 M solution (600 ml) of s-outyllithium in hexane, which had been cooled to -78°C and stirred. The stirring was ccnlinued for 1 hr and N,N-dimethylformamide (57 ml) was added dropwise. After completion

of t±ie dropwise addition, 2N aqueous hydrochloric acid (600
ml) was added and the mixture was allowed to warm to room
temperature. This was extracted with hexane and washed with
water and saturated brine. The organic layer was dried over
sodium sulfate and sodium sulfate was filtered off. The
filtrate was concentrated to give the title compound (61.54 g,
52%) .
^HNMR(CDCl3, 300MHz)5: 2.56(s, 3H), 7.14(d, J=10.7Hz, IH),
8.15(d, J=6.8Hz, IH), 10.32 (s, IH) .
b) ethyl trans-8{4-[(N-ethylamino)methyl]cyclohexyl)acetate
b-1) trans-4-(ethoxycarbonylmethyl)cyclohexanecarboxylic acid
To a solution (600 ml) of ethyl 4-oxocyclohexanecarboxylate (150 g) in ethanol was added sodiiom hydroxide (38.8 g) with stirring at room temperature. The reaction solution was stirred for 1 hr and ethyl diethylphosphonoacetate (192 ml) was added. To this reaction solution was added dropwise 21% sodium ethoxide/ethanol solution (363 ml) with stirring under ice-cooling over 1 hr. The stirring was continued for 1 hr and acetic acid (126 ml) was added. Then ammonium formate (111 g) and palladium carbon (5%, 15 g) were added and the mixture was stirred at 60°C for 6 hr with heating. The reaction solution was allowed to return to room temperature and insoliible materials were filtered off through celite. The filtrate was concentrated and the obtained residue was diluted with ethyl acetate. The mixture was washed successively with 2N aqueous hydrochloric acid, water and saturated brine. The organic layer was dried over sodiiam sulfate and sodium sulfate was filtered off. The filtrate was concentrated to give a crudely purified product (180.4 g) of the title compound. b-2) ethyl trans-[4-(N-ethylcarbamoyl)cyclohexyl]acetate
To a solution (200 ml) of the crudely purified product (180.4 g) of trans-4-

(ethoxycarbonylmethyl)cyclohexanecarboxylic acxd obtained in b-1) in tetrahydrofuran was added thionyl chloride (74 ml) with stirring at room temperature. The reaction solution was stirred for 3 hr and concentrated to give an- acid chloride. A solution (80 ml) of the above-mentioned acid chloride in tetrahydrofuran was added dropwise to tetrahydrofuran (250 ml) and 70% aqueous ethylamine (250 ml) with stirring under ice-cooling. This reaction solution was stirred for 30 rain and water (800 ml) was added. The mixture was extracted with ethyl acetate and the extract was washed successively with water and saturated brine. The organic layer was dried over sodium sulfate and sodium sulfate was filtered off. The filtrate was concentrated and the obtained residue was recrystallized from hexane-ethyl acetate to give the title compound (78.9 g, yield from ethyl 4-oxocyclohexanecarboxylate 37%).
^HNMR(CDCl3, 300MHz)5: 0.90-1.10(m, 2H), 1.13(t, J=7.3Hz, 3H), 1.25(t, J=7.1Hz, 3H), 1.40-1.60(m, 2H), 1.72-1.95(m, 5H), 1.99(m, IH), 2.19(d, J=6.8Hz, 2H), 3.28(m, 2H), 4.13(q, J=7.1Hz, 2H), 5.39(brs, IH). b-3) ethyl trans-8{4-[(N-ethylamino)methyl]cyclohexyl}acetate
To a suspension (800 ml) of ethyl trans-[4-(N-ethylcarbamoyl) cyclohexyl] acetate (100 g) and sodiiam borohydride (75.2 g) in tetrahydrofuran was added dropwise acetic acid (114 ml) over 1 hr with stirring under reflux, and the reaction solution was further stirred for 2 hr. The reaction solution was quenched by dropwise addition of water (200 ml) with stirring under ice-cooling. 1.5N Aqueous sodixom hydroxide (1000 ml) was added. The mixture was extracted with ethyl acetate and the extract was washed successively with water and saturated brine. The organic layer was dried over sodium sulfate and sodium sulfate was filtered off. The filtrate was concentrated and the obtained residue was dissolved in ethanol (500 ml). 4N Hydrochloric acid-ethyl

acetate (125 ml) was addfed dropwise with stirring at room temperature, and the stirring was continued for 20 hr. The reaction mixture was diluted with ethyl acetate and washed successively with 2N aqueous sodium hydroxide, water and saturated brine. The organic layer was dried over sodi\am sulfate and sodium sulfate was filtered off. The filtrate was concentrated to give the title compound (81.9 g, 87%). ^HNMR(CDCl3, 300MHz)5: 0.82-1.08(m, 4H), 1.10(t, J=7.1Hz, 3H), 1.25(t, J=7.lHz, 3H), 1.37(m, IH), 1.66-1.88(m, 5H), 1.99(m, IH), 2.18(d, J=6.8Hz, 2H) , 2.44(d, J=6.6Hz, 2H), 2.62(q, J=7.1Hz, 2H), 4.12(q, J=7.IHz, 2H). c) ethyl trans-(4-{[N-(2-{[N"-[3,5-
bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-5-methyl-4-trifluoromethylphenyl)-N-ethylamino]methyl}cyclohexyl)acetate
c-1) ethyl trans-(4-{[N-ethyl-N-(2-hydroxymethyl-5-methyl-4-trif luoromethylphenyl) amino]methyl}cyclohexyl)acetate p-toluenesulfonate
A solution (470 ml) of 2-fluoro-4-methyl-5-trifluoromethylbenzaldehyde (47.03 g), ethyl trans-{4-[(N-ethylamino)methyl]cyclohexyl}acetate (57.05 g) and potassium carbonate (94.5 g) in toluene was heated under reflux for 48 hr. The reaction solution was allowed to return to room temperature and washed successively with water, aqueous potassivrai hydrogen sulfate cind saturated brine. The organic layer was dried over magnesium sulfate and magnesium sulfate was filtered off. Ethanol (100 ml) was added to the obtained solution and sodium borohydride (4.31 g) was added with stirring at room temperature. The reaction solution was stirred for 1 hr and aqueous ammonium chloride (200 ml) was added to allow for partitioning. The organic layer was washed successively with water and saturated brine, and dried over sodium sulfate. Sodium sulfate was filtered off and the

filtrate was concentrated. The obtained residue was dissolved
in diethyl ether (1060 ml) , and p-toluenesulfonic acid hydrate
(43.4 g) was added with stirring at room temperature. The
stirring was continued for 2 hr. The precipitated crystals
were collected by filtration and dried to give the title
compound (120 g, 32%).
^HNMR(CDCl3, 300MHz)5: 0.70-1.14(m, 4H), 1.21(t, J=7.1Hz, 3H),
1.23(t, J=7.1Hz, 3H), 1.42(m, IH), 1.50-1.78(m, 4H), 1.93(m,
IH), 2.09(d, J=6.7Hz, 2H), 2.36(s, 3H), 2.54(s, 3H), 3.10-
4.15(m, 4H), 4.09(q, J=7.1Hz, 2H), 4.85-5.25(m, 2H), 7.07(d,
J=8.0Hz, 2H) , 7.33 (s, IH) , 7.54 (s, IH) , 7.77(d, J=8.0Hz, 2H),
11.57(brs, IH).
c-2) ethyl trans-(4-{[N-(2-{[N"-[3,5-
bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-
yl)amino]methyl}-5-methyl-4-trifluoromethylphenyl)-N-
ethylamino]methyl}cyclohexy1)acetate
A solution of ethyl trans-(4-{[N-ethyl-N-(2-hydroxymethyl-5-methyl-4-trifluoromethylphenyl) amino]methyl}cyclohexyl)acetate p-toluenesulfonate (120 g) and sodium hydrogen carbonate (32.3 g) in toluene-water (480-480 ml) was stirred at room temperature for 30 min and partitioned. The organic layer was washed successively with water and saturated brine and dried over magnesium sulfate. Magnesium sulfate was filtered off and the resulting solution was added dropwise to a solution (360 ml) of thionyl chloride (17.65 ml) in toluene with stirring under ice-cooling. The stirring was continued at room temperature for 30 rain and pyridine (33 ml) was added to the reaction solution. The mixture was washed successively with water and saturated brine. The organic layer was dried over sodium sulfate and sodiiira sulfate was filtered off. The filtrate was concentrated and potassium t-butoxide (27.5 g) was added to a solution (900 ml) of the obtained residue and

5-{[3,5-bis(trifluororaethyl)benzyl]amino}-2-methyl-2H-tetrazole (69.7 g) obtained in Example 9 a) in N,N-dimethylformaraide with stirring at room temperature. The stirring was continued for 2 hr and saturated aqueous ammonium chloride was added. The mixture was extracted with ethyl acetate and the extract was washed successively with water and saturated brine. The organic layer was dried over sodium sulfate and sodium sulfate was filtered off. The filtrate was concentrated and the obtained residue was purified by column chromatography (n-hexane:ethyl acetate=4:l) to give the title compound (118 g, 80%) (see Table 34). Example 170
trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-5-methyl-4-trifluoromethylphenyl)-N-ethylamino]methyl}cyclohexyl)acetic acid
To a solution (326 ml) of ethyl trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-ff. The filtrate was concentrated. The obtained residue was jurified by column chromatography (n-hexane:ethyl acetate=2:l) :o give the title coir^jound (104 g, 92%) (see Table 34) . •iXninple 142
:rans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-■ieT:hyl-2H-tetrazol-5-yl) amino]methyl}-5-methy 1-4-

trifluoromethylphenyl) -N-ethylamino]inethyl}cyclohexyl) acetic acid hydrochloride
To a solution (1.5 ml) of trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethy1)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)araino]methyl}-5-methyl—4-trifluoromethylphenyl)-N-ethylamino]methylIcyclohexyl)acetic acid (130 mg) in ether was added IN hydrochloric acid-ether (0.20 ml) with stirring at room t«nperature. The precipitated solid was collected by filtration and dried to give the title compound (128 mg, 94%) (see Table 29). Example 168
trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-5-methyl-4-trifluoromethylphenyl)-N-ethylamino]methylIcyclohexyl)acetic acid methanesulfonate
To a solution (580 ml) of trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-5-methyl-4-trifluoromethylphenyl)-N-ethylamino]methyl}cyclohexyl)acetic acid (96.3 g) in ethyl acetate was added methanesulfonic acid (13.56 ml) with stirring at room temperature. The stirring was continued for 15 hr and the precipitated solid was collected by filtration and dried to give an ethyl acetate solvate of methanesulfonate. This was suspended in heptane-ethyl acetate (3:1, 990 ml) and the suspension was stirred with heating at 80°C for 20 hr, allowed to return to room temperature, filtered and dried to give the title compound (91.0 g, 83%) (see Table 34).
In a similar manner as in Examples 1-9, 142, 168, 169 and 170, the compounds of Examples 10-141 and 143-167 were obtained. These are shown in Tables 1-34 together with Examples 1-9, 142, 168, 169 and 170.






































































































Kxper1mPTTl-a1 Examples
The following tests were performed for the CETP activity inhibitory effect of the compound of the present invention. "reparation of Donor Lipoprotein
Potassium bromide (KBr) was added to plasma (40 mL) of lealthy subject and the mixture was adjusted to have a ip>ecific density d=1.125 g/mL. The mixture was subjected to
lensity gradient centrifugation {227,000xg, 4°C, 17 hr) and a ■raction showing a specific density of d>1.125 g/mL (HDL3 ■raction) was harvested. The obtained fraction was dialyzed igainst PBS solution [10 mmol/L Na2HP04; 10 mmol/L NaH2P04; 0.15 tol/L NaCl; 1 mol/L EDTA (pH 7.4)]. Then, tritium-labeled iholesterol (37 MBq) was dissolved in 95% ethanol, gradually .dded to the above-mentioned HDL3 fraction with stirring and
ncubated at 37°C for 18 hr. [By this operation, tritium-abeled cholesterol was esterified by the action of lecithin cyl transferase (LCAT) present on the HDL3 surface and taken p into HDL3 as tritium-labeled cholesteryl ester ([^H]CE)]. fter incubation, KBr was added, the mixture was adjusted to ave a specific density d=1.21 g/mL, subjected to density radient centrifugation (227,000xg, 4°C, 17 hr) and a fraction f specific density d>1.21 g/mL was harvested. The obtained raction was dialyzed against the aforementioned PBS solution o give HDL3 incorporating [^H]CE ( [^H] CE-HDL3, specific ensity: 1.125
Experimental Example 1: inhibitory effect in vitro on CETP activity in total plasma
The donor lipoprotein obtained above was added to plasma of healthy subject to prepare a [^H] CE-HDLj-containing plasma (1,000 dpm/^L) . The compound was dissolved in dimethyl formamide. A solution of the compound or a solvent alone (2 )iL) and the [^H]CE-HDL3-containing plasma (100 pi) were added into a microti±)e, and this was incubated at 37°C or 4°C for 4 hr. After ice-cooling, TBS solution [100 ^iL, 20 mmol/L Tris ; 0.15 mol/L NaCl (pH 7.4)] containing 1 mol/L magnesium chloride and 2% dextran sulfate was added to each microtube and the mixture was thoroughly stirred. After keeping at 4°C for 30 min, the mixture was centrifuged (10,000xg, 4°C, 10 min) , and the radioactivity in the obtained supernatant (HDL fraction) was measured with a scintillation counter. The difference in the measurement values obtained by incubation of solvent alone at 4°C and. 37°C was taken as CETP activity, and the proportion of decrease in the difference in the measurement values of specimen was taken as percent inhibition of CETP activity. The concentration of the compound necessary for inhibiting the CETP activity by 50% was calculated as an IC50 value. The results are shown in the following.





Experimental Example 2: inhibitory effect exo vivo on CETP activity in total plasma of normal hamster
The compound of the present invention was suspended in 0.5% methyl cellulose solution and orally administered once to a healthy hamster with a plastic gavage needle. Blood was taken at 2 or 4 hr after the administration and CETP activity in plasma was measured according to the following method.
The donor lipoprotein obtained above was added to hamster plasma (100 )iL) to prepare [^H] CE-HDLs-containing plasma (ca. 1,000 dpm/^L) . The [^H] CE-HDLs-containing plasma was dispensed to two microtubes by 25 }j,L each, and one was incubated at 37°C and the c-^"^"- "-^^ ^„„„K-,4-^^ -,+- Aon for 4 hr

eacn. Arrer ice-cooxing, Ttm soiurion (DU (ii/; conraining 1 mol/L magnesium chloride and 2% dextran sulfate was added to each microtube and the mixture was thoroughly stirred. After keeping at 4°C for 30 min, the mixture was centrifuged (10,000xg, 4°C, 20 min), and the radioactivity in the obtained supernatant (HDL fraction) was measured with a liquid scintillation counter. The radioactivity of the [^HJCE-HDLs-containing plasma was measured with a liquid scintillation counter, and taken as the total radioactivity. The transfer rate of [^H]CE was calculated from the following formula using the total radioactivity (Total count), radioactivity by 37°C incubation (37°C count) and radioactivity by 4°C incubation (4°C count) of the sample of each individual and taken as the CETP activity.
ZETP activity (transfer ratio (%)) = { [ (4°C count)-(37°C zount)]/(Total count)}xlOO
The CETP activity inhibitory ratio of each compound administration group based on the CETP activity of the solvent idministration group as 100% was calculated from the following formula and expressed in %.
:ETP activity inhibitory ratio (%) = 100-[(CETP activity of sach con^xaund administration group)/(CETP activity of solvent idministration group)xlOO]
The results are shown in the following.



values.
Experimental Example 3: blood HDL cholesterol increasing effect in normal hcimster
To the plasma (40 p.L) obtained from the above-mentioned animal at 4 or 8 hr after the administration was added 15% polyethylene glycol solution (40 j^L) and the mixture was thoroughly stirred. After keeping at room temperature for 10 min, the mixture was centrifuged (10,000xg, 4°C, 20 min) and the cholesterol content (HDL cholesterol content) of the obtained supernatant (HDL fraction) was measured. The increase ratio of the HDL cholesterol content of each compound administration group when the HDL cholesterol content of the

solvent administration group as 100% was calculated from the following formula and expressed in %.
HDL cholesterol increase ratio {%)= [(HDL cholesterol content of each compound administration group/HDL cholesterol content of solvent administration group)xlOO]-100
The results are shown in the followina.
values.
Experimental Example 4: concomitant use test
For the experiment, 10-week-old male Japanese white rabbits (manufactured by KITAYAMA LABES Co., Ltd.) were used. The animal was acclimated on normal food (RC-4, manufactured by Oriental Bio-Service Co.) and fasted for 24 hr and a high cholesterol food (0.25% cholesterol-added RC-4, manufactured by Oriental Bio-Service Co.) was given by 100 g/day per rabbit (preliminary feeding) for 3 days. On the next day of day 3 of preliminary feeding, blood was taken from the auricular artery before feeding, and the animals were grouped by 6 rabbits per group based on the parameters (HDL cholesterol content, total cholesrerol content, triglyceride content) of plasma and body

weight.
Foods were prepared (manufactured by Oriental Bio-Service Co.) by adding simvastatin (0.002%), compound (0.2%) of Example 168, or simvastatin (0.002%) + compound (0.2%) of Example 168 to a high cholesterol food, and each food was given to the grouped animals by 100 g/day per rabbit for 15 days. At 8 hr after feeding on day 15, the total blood was taken from the carotid artery under anesthesia, HDL cholesterol content, total cholesterol content and ApoA-I content in plasma were measured. The arteriosclerosis index was calculated from [(total cholesterol content-HDL cholesterol content)/HDL cholesterol content]. Furthermore, the HDL3 fraction was separated from plasma by ultracentrifugation and the cholesterol content of the fraction was measured. In Table, arteriosclerotic index, ApoA-I content and HDL3 cholesterol content are shown based on the value of the control group as 100%.

Industrial Applicability
From the foregoing test results and the like, the

compound and a salt thereof of the present invention have superior CETP activity inhibitory effect. Therefore, they can decrease IDL, VLDL and LDL that promote arteriosclerosis and increase HDL that acts suppressively. As a result, they are useful as prophylactic or therapeutic agents for hyperlipidemia. In addition, they are useful as prophylactic or therapeutic agents for arteriosclerotic disease and the like.
Moreover, concurrent use of the confound of the present invention with a different therapeutic agent for hyperlipidemia (statin pharmaceutical agent) is expected to promote increase in HDL cholesterol, decrease arteriosclerotic index particularly remarkably, and show extremely superior synergistic effect. Therefore, it is clear that the compound of the present invention can be used concurrently with a different pharmaceutical agent, particularly other therapeutic agents for hyperlipidemia, arteriosclerosis, coronary artery disease, obesity, diabetes or hypertension.
This application is based on patent application Nos. 255604/2002 and 1071610/2003 filed in Japan, the contents of which are hereby incorporated by reference.


WE CLAIM :
^^ A dibenzylamine compound represented by the formula (1):

wherein
R^ and R^
are the same or different and each is a halogen atom, a nitro group, a cyano group or a Ci,^ alkyl group optionally substituted by halogen atoms;
R^ R^ and R*
are the same or different and each is a hydrogen atom, a halogen atom, a Cj-s alkyl group optionally substituted by halogen atoms, a Ci-e alkylthlo group optionally substituted by halogen atoms or a Ci-6 alkoxy group optionally sxibstituted by halogen atoms, or R^ and R^ or R* and R^ may form, together with a carbon atom bonded thereto, a carbocyclic ring or a heterocyclic ring, each optionally substituted by halogen atom(s); is -N(R^) (R^) wherein
R^ and R® are the same or different and each is a Ci-e alkyl group
wherein the Ci-e alkyl group is optionally
substituted by - (CHz)„-COOR^
wherein R" is a hydrogen atom or a Ci-e
177

alkyl group and m is 0 or an integer of 1 to 5, or a C^-io cycloalkylalkyl group
wherein the C4.10 cycloalkylalkyl group is optionally substituted by Ci-e alkyl group wherein the Ci-e alkyl group is optionally substituted by hydroxyl group, C1..6 alkoxy group or phosphono group, -(CH2)q-C0N(R") (R")
wherein R^"" and R^^ are the same or different and each is hydrogen atom or Cx-e alkyl group and q is 0 or an integer of 1 to 5/ or - (CH2) r-COOR"
wherein R^° is hydrogen atom or Ci-e alkyl group and r is 0 or an integer of 1 to 5/ -C(R") (R") (R^3)
wherein R^^, R-"^ and R" are the same or different and each is a hydrogen atom, a Ci-e alkyl group or a C4-ao cycloalkylalkyl group
wherein the C4.10 cycloalkylalkyl group is optionally substituted by -(CH2)r-CCX)R^°
wherein R^" and r are as defined above, or -0-C{R") (R") (B}^y
wherein R", R^^ and R" are the same or different and each is a hydrogen atom or a Ci-e alkyl group, wherein the Ci-e alkyl group is optionally substituted by -COOR"
wherein R* is as defined above; ring B is an aryl group or a heterocyclic residue containing
hetero atom(s) selected from N, 0 and S;
\^ is a hydrogen atom, a halogen atom, a Ci-g alkoxy group,
a C2-6 alkenyl group or a Ci-g alkyl group optionally

substituted by hydroxyl group; and n is an integer of 1 to 3 or a pharmaceutically acceptable salt thereof.
The dibenzylamine compound as claimed in claim 1
wherein
R\ R* and R^
are the same or different and each is a hydrogen atom/ a halogen atom, a Ci-6 alkyl group optionally substituted by halogen atoms or a Ci-e alkoxy group optionally substituted by halogen atoms,, or R^ and R^ or R* and R^ may form, together with a carbon atom bonded thereto, a carbocyclic ring or a heterocyclic ring, each optionally substituted by halogen atom(s); is -N(R") (R^) wherein
R"" and R® are the same or different and each is a a Ci.6 alkyl group
wherein the Ci-e alkyl group is optionally substituted by -COOR*
wherein R* is as defined in claim 1, or a C4.10 cyclbalkylalkyl group
wherein the C4.10 cycloalkylalkyl group is optionally substituted by Ci.e alkyl group wherein the Ci-s alkyl group is optionally substituted by hydroxyl group, Ci-e alkoxy group or phosphono group, or -{CH2)r-C00R"
wherein R^° and r are as defined in claim 1, -C(R") (R"^) (R^^)
wherein R^ , R" and R are the same or different and each is a hydrogen atom, a Ci-e alkyl group or

a C4-10 cycloalkylalkyl group
wherein the C4-io cycloalkylalkyl group is optionally substituted by - (CHz) r-COOR^""
wherein R^° and r are as defined in claim 1/ or -0-C(R") (R") (R")
wherein R", R^^ and R" are the same or different and each is a hydrogen atom or a Ci-6 alkyl group, wherein the Ci-e alkyl group is optionally substituted by -COOR"
wherein R" is as defined in claim 1; R^ is a hydrogen atom, a halogen atom, a Ci-e alkoxy
group or a Ci-e alkyl group optionally substituted by hydroxyl group, or a pharmaceutically acceptable salt thereof,
3. The dibenzylamine compound as claimed in claim 2, wherein R^ is a Ci.e alkyl group substituted by a halogen atom, or a
pharroaceutically acceptable salt thereof.
20
4 ^ The dibenzylamine compound as claimed in claim 3, wherein R^ is a trifluoromethyl group, or a pharmaceutically acceptable salt thereof.
5. The dibenzylamine compound as claimed in claim 4, wherein ring B and (R*)n are each


wherein R*°, R*^ and R*^ are the same or different and each is a hydrogen atom, a halogen atom, a Ci-e alkoxy group, a C2-6 alkenyl group or a Ci-e alkyl group optionally substituted by hydroxyl group, or a pharmaceutically acceptable salt thereof.
6. The dibenzylamine compound as claimed in claim 5, wherein ring B and (R*)n are each


wherein R®°, R" and R*^ are as defined in claim 5, or a pharmaceutically acceptable salt thereof.
7. The dibenzylamine compound as claimed in claim 6, wherein ring B and
(R*)„ are each

wherein R^° and R*^ are as defined in claim 5, or a pharmaceutically acceptable salt thereof.
8. The dibenzylamine compound as claimed in claim 7, wherein A is
N(R"") (R^) (wherein R" and R^ are as defined in claim 1), or a
pharmaceutically acceptable salt thereof.
9. The dibenzylamine compound as claimed in claim 8, wherein R^ is a Ci-e
alkyl group, or a pharmaceutically acceptable salt thereof.
10. The dibenzylamine compound as claimed in claim 9, wherein R® ig ^ Cj.g
alkyl group, or a pharmaceutically acceptable salt thereof.

11 "The dibenzylamine compound as claimed in claim 1, which is selected from the group consisting of
N-[3-(N"-cyclopentylmethyl-N"-ethylamino)-5,6,7,8-tetrahydronaphthalen-2-ylmethyl]-N-[3,5-
bis(trifluoromethyl)benzyl]-(2-methyl-2H-tetrazol-5-yl)amine, 3-{[N-[3-(N"-cyclopentylmethyl-N"-ethylamino)-5,6,7,8-tetrahydronaphthalen-2-ylmethyl]-N-(2-methyl-2H-tetrazol-5-yl)amino] methyl}-5-trifluoromethylbenzonitrile, N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-(2-methyl-2H-tetrzol-5-yl)amine,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino) indan-5-ylmethyl]-(2-methyl-2H-tetrazol-5-yl)amine hydrochloride,
N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-N-(2H-tetrazol-5-yl)-[3,5-bis(trifluoromethyl)benzyl]amine, N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-N-13,5-bis (trif luoromethyl) benzyl] - (pyriniidin-2-yl) amine hydrochloride,
N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-N-[3,5-bis(trifluoromethyl)benzyl]-(5-methyl-lH-pyrazol-3-yl)amine,
5-{N-(6-{[N"-t3,5-bis(trifluoromethyl)benzyl]-N"-(5-methyl-[1,2,41oxadiazol-3-yl)amino]methyl}indan-5-yl)-N-ethylamino}pentanoic acid hydrochloride, methyl trans-4-{[N-(2-{[N"-[3,5-bis(trifluoromethvl)benzvll-

N"-(2-methyl-2H-tetra2ol-5-yl)amino]methyl}-4-trifluororaethoxyphenyl)-N-ethylamino]methyl}cyclohexanecarboxylate, 3-{[N-[6-{N"-cyclopentylraethyl-N"-et±iylamino)indan-5-ylmethyl]-N-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-5-trifluororaethylbenzonitrile,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino) indan-5-ylmethyl]-(2-ethyl-2H-tetrazol-5-yl)amine,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylaraino)indan-5-ylmethyl]-(1-methyl-lH-[1,2,4]triazol-3-yl)amine,
3-({N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-N-phenylamino}methyl)-5-trifluororaethylbenzonitrile, 3-{[N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-N-(4,5-dimethyl-thiazol-2-yl)amino]methyl}-5-trifluoromethylbenzonitrile,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino) indan-5-ylmethyl]-(thiazol-2-yl)amine hydrochloride,
3-({N-[6-(N"-cyclopentylmethyl-N"-ethylamino) indan-5-ylmethyl]-N-(thiazol-2-yl)amino}methyl)-5-trifluoromethylbenzonitrile hydrochloride,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentyImethyl-N"-ethylamino)indan-5-ylmethyl]-(oxazol-2-yl)amine hydrochloride,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentyImethyl-N"-ethylamino)indan-5-ylmethyl]-(5-methylthiazol-2-yl)amine hydrochloride,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentyImethyl-N"-ethylamino)indan-5-ylmethyl]-(4-methylthiazol-2-yl)amine hydrochloride, N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentyImethyl-

N"-ethylamino)indan-5-ylmethyl]-(4,5-dimethylthiazol-2-yl)amine hydrochloride,
3-{[N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-N-(5-methylthiazol-2-yl)amino]methyl}-5-trifluoromethylbenzonitrile hydrochloride, 3-{[N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-N-(4-methylthiazol-2-yl) aminoJmethyl}-5-trifluoromethylbenzonitrile hydrochloride,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino) indan-5-ylmethyl]-(4-methyloxazol-2-yl)amine hydrochloride,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-(3-methylisothiazol-5-yl)amine hydrochloride,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino) indan-5-ylmethyl]-(5-methylisoxazol-3-yl)amine hydrochloride,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino).indan-5-ylmethyl] - (3-methylisoxazol-5-yl) amine hydrochloride,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-(l-methyl-lH-pyrazol-3-yl)amine hydrochloride,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indem-5-ylmethyl]-(l-methyl-lH-pyrazol-4-yl)amine hydrochloride,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-(5-methyl-[1,3,4]thiadiazol-2-y 1) eimine hydrochloride,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-yImethy1]-(5-methyl-[1,3,4]oxadiazol-2-yl)amine hydrochloride, N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-

N"-ethylamino)indan-5-ylmethy1]-pyridin-3-ylamine hydrochloride,
N-[3,5-bis(trifluoromethy1)benzyl]-N-[6-(N"-cyclopentylmethy1-N"-ethylamino)indan-5-ylmethyl]-pyridin-2-ylamine hydrochloride,
N-[3,5-bis(trifluoromethy1)benzyl]-N-[2-(N"-cyclopentylmethyl-N"-ethylamino)-5-trifluoromethyIbenzyl]-(2-methyl-2H-tetrazol-5-yl)amine hydrochloride,
3-{[N-[2-(N"-cyclopentylmethyl-N"-ethylamino)-5-trifluoromethyIbenzyl]-N-{2-methyl-2H-tetrazol-5-yl)amino]methyl}-5-trifluoromethyIbenzonitrile hydrochloride, methyl 5-[N-(6-{[N"-[3,5-bis(trifluororaethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl) amino]methyl}indan-5-yl)-N-ethylamino]pentanoate hydrochloride,
methyl 5-[N-(6-{[N"-(3-cyano-5-trifluoromethyIbenzyl)-N"-(2-methyl-2H-tetrazol-5-yl)aminojmethyl}indan-5-ylmethyl)-N-ethylamino]pentanoate hydrochloride,
methyl 5-[N-(6-{[N"-[3,5-bis(trifluoromethy1)benzyl]-N"-(1-methyl-lH-pyrazol-3-yl)amino]methyl}indan-5-yl)-N-ethylamino]pentanoate hydrochloride,
5- [N- (6- {[N"-13,5-bis (trif luoromethy 1) benzyl] -N"- (2-methyl-2H-tetrazol-5-yl)amino]methyl}indan-5-yl)-N-ethylamino]pentanoic acid hydrochloride,
5-[N-(6-{[N"-(3-cyano-5-trifluoromethyIbenzyl)-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}indan-5-yl)-N-ethylamino]pentanoic acid hydrochloride, 5-[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(3-methylisoxazol-5-yl) amino]methyl)indan-5-yl)-N-ethylamino]pentanoic acid hydrochloride,
5-[N-(6-{[N"-[3,5-bis(trifluoromethy1)benzyl]-N"-(1-methyl-lH-pyrazol-3-yl)amino]methyl}indan-5-yl)-N-ethylamino]pentanoic acid hydrochloride, methyl trans-4-{[N-(3-{[N"-[3,5-bis(trifluoromethyl)benzyl]-

N"-(l-methyl-lH-pyrazol-3-yl)amino]methyl}-5,6,7,8-tetrahydronaphthalen-2-yl)-N-
ethylamino]methyl}cyclohexanecarboxylate hydrochloride, methyl trans-4-{[N- (3-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-(l-methyl-lH-pyrazol-3-yl)amino]methyl}-5,6,7,8-tetrahydronaphthalen-2-yl) -N-
ethylamino]methyl}cyclohexanecarboxylate hydrochloride, trans-4-{[N-(3-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(1-methyl-lH-pyrazol-3-yl)amino]methyl}-5,6,7,8-tetrahydronaphthalen-2-yl)-N-
ethylaminoJmethylIcyclohexanecarboxylie acid hydrochloride, trans-4-{[N-(3-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-(1-methyl-lH-pyrazol-3-yl)amino]methyl}-5,6,7,8-tetrahydronaphthalen-2-yl)-N-
ethylamino]methylIcyclohexanecarboxylie acid hydrochloride, N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N "-ethylamino)indan-5-ylmethyl]-(5-methyl-[1,2,4]oxadiazol-3-yl)amine hydrochloride,
methyl trans-4-{[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(l-methyl-lH-pyrazol-3-yl)amino]methyl}indan-5-yl)-N-ethylamino]methyl}cyclohexaneearboxylate hydrochloride, trans-4-{[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(l-methyl-lH-pyrazol-3-yl)amino]methyl}indan-5-yl)-N-ethylamino]methyl Jcyclohexaneearboxylic acid hydrochloride, methyl trans-4-{[N-(6-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-(l-methyl-lH-pyrazol-3-yl)amino]methyl}indan-5-yl)-N-ethylamino]methyl)eyclohexaneearboxylate,
trans-4-{[N-(6-{[N"-(3-eyano-5-trifluoromethylbenzyl)-N"-(1-methyl-lH-pyrazol-3-yl)amino]methyl}indan-5-yl)-N-ethylamino]methyl}cyclohexaneearboxylic acid hydrochloride, trans-4-{[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}indan-5-yl)-N-ethylamino]methyl}cyclohexaneearboxylic acid hydrochloride.

trans-4-{ [N- (6-{ [N"- (3-cyano-5-trifluoromethylbenzyl) -N"- (2-methyl-2H-tetra2ol-5-yl) ainino]methyl}indan-5-yl) -N-ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride, trans-4-{[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(3-methylisoxazol-5-yl) ainino]met±yl }indan-5-yl)-N-ethylaininolmethyl}cyclohexanecarboxylic acid hydrochloride, trans-4-{[N-(6-{ [N"- (3-cyano-5-trifluoromethylbenzyl)-N"-(3-methylisoxazol-S-yl) ainino]methyl}indan-5-yl) -N-ethylamino]methyl}cyclohexanecarboxylie acid hydrochloride, methyl 5-[N-(6-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-(1-methyl-lH-pyrazol-3-yl)amino]methyl}indan-5-yl)-N-ethylamino]pentanoate hydrochloride,
5-[N-(6-{[N"-(3-cyano-5-trifluororaethylbenzyl)-N"-(3-raethyl-isoxazol-5-yl)amino]methyl}indan-5-yl)-N-ethylamino]pentanoic acid hydrochloride,
5-[N-(6-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-(1-methyl-lH-pyra2ol-3-yl)amino]methyl)indan-5-yl) -N-ethylaminojpentanoic acid hydrochloride,
5-[N-(6-{[N"-[3,5-bis (trifluoromethyl)benzyl]-N"-(1-methyl-lH-[1,2,4]triazol-3-yl)amino]methyl}indan-5-yl)-N-ethylamino]pentanoic acid hydrochloride,
trans-4-{[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(1-methyl-lH-[1,2,4]triazol-3-yl)amino]methyl}indan-5-yl)-N-ethylamino]methyl}cyclohexanecarboxylie acid hydrochloride, trans-4-{[N-(6-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-(l-methyl-lH-[l,2,4]triazol-3-yl) amino]methyl}indan-5-yl) -N-ethylamino]methyl}cyclohexanecarboxylic acid,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino) indan-5-ylmethyl]-(3-methyl-[1,2,4]thiadiazol-5-yl)amine,
5-[N-(6-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-(1-methyl-IH-[1,2,4]triazol-3-yl)amino]methyl}indan-5-yl)-N-ethylamino]pentanoic acid hydrochloride.

methyl 5-[N-(3-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(1-
methyl-lH-pyrazol-3-yl)amino]methyl}-5,6,7,8-
tetrahydronaphthalen-2-yl)-N-ethylamino]pentanoate
hydrochloride,
methyl 5-[N-(3-{[N"- (3-cyano-5-trifluoromethylbenzyl)-N"-(1-
methyl-lH-pyrazol-3-yl)amino]methyl}-5,6,7,8-
tetrahydronaphthalen-2-yl)-N-ethylamino]pentanoate
hydrochloride,
5-[N-(3-{[N"-[3,5-bis (trifluoromethy1)benzyl]-N"-(1-methy1-lH-
pyrazol-3-yl)amino]methyl}-5,6,7,8-tetrahydronaphthalen-2-yl) -
N-ethylamino]pentanoic acid hydrochloride,
5- [N- (3-{ [N""- (3-cyano-5-trifluoromethylbenzyl) -N"- (1-methyl-
lH-pyrazol-3-yl)amino]methyl}-5,6,7,8-tetrahydronaphthalen-2-
yl)-N-ethylamino]pentanoic acid hydrochloride,
trans-4-{[N-(3-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
raethyl-2H-tetrazol-5-yl)amino]methyl}-5,6,7,8-
tetrahydronaphthalen-2-yl)-N-
ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride,
trans-4-{[N-(3-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-(2-
methyl-2H-tetrazol-5-yl)amino]methyl}-5,6,7,8-
tetrahydronaphthalen-2-yl)-N-
ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride,
trans-4-{[N-(3-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(1-
methyl-lH-[1,2,4]triazol-3-yl)amino]methyl}-5,6,7,8-
tetrcihydronaphthalen-2-yl)-N-
ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride,
trans-4-{[N-(3-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-(l-
methyl-lH-[1,2,4]triazol-3-yl)amino]methyl}-5,6,7,8-
tetrahydronaphthalen-2-yl)-N-
ethylamino]methyl}cyclohexanecarboxylic acid,
trans-4-{[N-(3-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(3-
methylisoxazol-5-yl)amino]methyl}-5,6,7,8-
tetrahydronaphthalen-2-yl)-N-

ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride,
trans-4-{[N-(3-{[N"-(3-cyanb-5-trifluoromethylbenzyl)-N"-(3-
methylisoxazol-5-yl)amino]methyl}-5,6,7,8-
tetrahydronaphthalen-2-yl)-N-
ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride,
2-(5-{N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-
cyclopentylraethyl-N"-ethylamino)indan-5-
ylmethyl]amino}tetrazol-2-yl)ethanol hydrochloride,
methyl 5-[N-{3-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(1-
methyl-lH-[1,2,4]triazol-3-yl)amino]methyl}-5,6,7,8-
tetrahydronaphthalen-2-yl)-N-ethylamino]pentanoate
hydrochloride,
methyl 5-[N-{3-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-(1-
methyl-lH-[1,2,4]triazol-3-yl)amino]methyl}-5,6,7,8-
tetrahydronaphthalen-2-yl)-N-ethylamino]pentanoate
hydrochloride,
5-[N-(3-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(1-methy1-lH-
[1,2,4]triazol-3-yl)amino]methyl}-5,6,7,8-
tetrahydronaphthalen-2-yl)-N-ethylamino]pentanoic acid
hydrochloride,
5-[N-(3-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-(1-methyl-
IH-[1,2,4]triazol-3-yl)amino]methyl}-5,6,7,8-
tetrahydronaphthalen-2-yl)-N-ethylamino]pentanoic acid
hydrochloride,
5-[N-(3-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(3-
methylisoxazol-5-yl)amino]methyl}-5,6,7,8-
tetrahydronaphthalen-2-yl)-N-ethylamino]pentanoic acid
hydrochloride,
5-[N-(3-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"- (3-
methylisoxazol-5-yl)amino]methyl}-5,6,7,8-
tetrahydronaphthalen-2-yl)-N-ethylamino]pentanoic acid
hydrochloride,
5-[N-(3-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-

tetrazol-5-yl)amino]methyl}-5,6,7,S-tetrahydronaphthalen-Z-
yl)-N-ethylamino]pentanoic acid hydrochloride,
5-[N-(3-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-(2-methyl-
2H-tetrazol-5-yl)amino]methyl}-5,6,7,8-tetrahydronaphthalen-2-
yl)-N-ethylamino]pentanoic acid hydrochloride,
trans-4-{[N-(6-{[N"-t3,5-bis(trifluoromethyl)benzyl]-N"-(5-
methyl-[1,2,4]oxadiazol-3-yl)amino]methyl}indan-5-yl)-N-
ethylamino]methyl}cyclohexanecarboxylic acid,
5-[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(1-methyl-lH-
pyrazol-3-yl)amino]methyl)-4-trifluoromethoxyphenyl)-N-
ethylamino]pentanoic acid hydrochloride,
5-[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(l-methyl-lH-
pyrazol-3-yl)amino]methyl}-4-trifluoromethylphenyl)-N-
ethylamino]pentanoic acid hydrochloride,
5-[N-(2-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-(1-raethyl-
lH-pyrazol-3-yl)amino]methyl}-4-trifluoromethylphenyl)-N-
ethylamino]pentanoic acid hydrochloride,
5-[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-
tetrazol-5-yl)amino]methyl)-4-trifluororaethylphenyl)-N-
ethylamino]pentanoic acid hydrochloride,
5-[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-ethyl-2H-
tetrazol-5-yl)amino]methyl}indan-5-yl)-N-ethylamino]pentanoic
acid hydrochloride,
5-{N-[6-({N"-[3,5-bis(trifluoromethyl)benzyl]-N"-[2-(2-
hydroxyethyl)-2H-tetrazol-5-yl]amino)methyl)indan-5-yl]-N-
ethylamino}pentanoic acid hydrochloride,
5-[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-
tetrazol-5-yl)amino]methyl}-4-trifluoromethoxyphenyl)-N-
ethylaminojpentanoic acid hydrochloride,
5-[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-
tetrazol-5-yl)amino]methyl}indan-5-yl)-N-ethylamino]-2,2-
dimethylpentanoic acid hydrochloride,
6-[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-

tetrazol-5-yl) amino] methyl }indan-5-yl) -N-ethylamino] hexanoic acid hydrochloride,
5-[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}indan-5-yl)-N-ethylamino]-3,3-dimethylpentanoic acid hydrochloride,
trans-4-{[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-{2-ethyl-2H-tetrazol-5-yl)amino]methyl}indan-5-yl)-N-ethylamino]methyl)cyclohexanecarboxylic acid hydrochloride, (l-{2-[N-(6-{[N"-[3,5-bis (trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}indan-5-yl)-N-ethylamino]ethyl}cyclopentyl)acetic acid hydrochloride, trans-4-({N-[6- ({N"-[3,5-bis(trifluoromethyl)benzyl]-N"-[2-(2-hydroxyethyl)-2H-tetrazol-5-yl]amino}methyl)indan-5-yl]-N-ethylamino}methyl)cyclohexanecarboxylic acid, trans-4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl) cunino]methyl)-4-trifluoromethylphenyl)-N-
ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride, (l-{2-tN-(3-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-5,6,7,8-tetrahydronaphthalen-2-yl)-N-ethylamino]ethyl}cyclopentyl)acetic acid,
trans-4-{[N-(2-{[N"-[3,5-bis(trifluororaethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-4-trifluoromethoxyphenyl)-N-
ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride, trans-4-{[N-(3-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-ethyl-2H-tetrazol-5-yl)amino]methyl}-5,6,7,8-tetrahydronaphthalen-2-yl)-N-
ethyleimino]methyl}cyclohexanecarboxylic acid hydrochloride, trans-4-({N-[3-({N"-[3,5-bis (trifluoromethyl)benzyl]-N"-[2-(2-hydroxyethyl)-2H-tetrazol-5-yl] amino}methyl) -5,6,7,8-tetrahydronaphthalen-2-yl]-N-

ethylamino}methyl)cyclohexanecarboxylic acid hydrochloride,
1-{3-[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-
2H-tetrazol-5-yl) aniino]methyl}indan-5-yl) -N-
ethylainino]propyl}cyclohexanecarboxylic acid hydrochloride,
5-[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(1-methyl-lH-
pyrazol-3-yl)amino]methyl}indan-5-yl)-N-ethylamino]-3,3-
dimethylpentanoic acid,
5-[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(5-methyl-
[1,2,4]oxadiazol-3-yl)amino]methyl}indan-5-yl)-N-ethylamino]-
3,3-dimethylpentanoic acid hydrochloride,
5-[N-(2-{[N"-[3,5-bis (trifluoromethyl)benzyl]-N"-(2-raethyl-2H-
tetrazol-5-yl)amino]methyl)-4-trifluoromethoxyphenyl)-N-
ethylamino]-3,3-dimethylpentanoic acid hydrochloride,
5-[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-raethyl-2H-
tetrazol-5-yl)amino]methyl}-4-trifluoromethylphenyl)-N-
ethylamino]-3,3-dimethylpentanoic acid hydrochloride,
trans-4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(1-
methyl-lH-pyrazol-3-yl)amino]methy1}-4-
trifluoromethoxyphenyl)-N-
ethylaraino]methyl)cyclohexanecarboxylic acid hydrochloride,
5-[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(l-methyl-lH-
pyrazol-3-yl)amino]methyl}-4-trifluoromethoxyphenyl)-N-
ethylamino]-3,3-dimethylpentanoic acid hydrochloride,
5-[N-(2-{[N"-[3,5-bis (trifluoromethyl)benzyl]-N"-(5-methy1-
[l,2,4]oxadiazol-3-yl)amino]raethyl}-4-trifluoromethoxyphenyl) -
N-ethylamino]-3,3-dimethylpentanoic acid hydrochloride,
trans-4-{[N-(2-{ [N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(5-
methyl-[1,2,4]oxadiazol-3-yl)amino]methyl}-4-
trifluoromethoxyphenyl)-N-
ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride,
6-[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-
tetrazol-5-yl)amino]methyl}-4-trifluoromethoxyphenyl)-N-
ethylaminojhexanoic acid hydrochloride.

trans-(4-{[N-(6-{[N"-[3,5-bis(trifluororaethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}indan-5-yl)-N-ethylaraino]methyl}cyclohexyl)acetic acid hydrochloride, 6-[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}indan-5-yl)-N-ethylaraino]-4,4-dimethylhexanoic acid hydrochloride,
6-[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}indan-5-yl)-N-ethylamino]-3,3-dimethylhexanoic acid hydrochloride,
5-[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl) eunino]methyl}indan-5-yl)-N-ethylamino]-4,4-dimethylpentanoic acid hydrochloride,
trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)araino]methyl}-4-trif luoromethoxyphenyl) -N-ethylamino]methyl}cyclohexyl)acetic acid hydrochloride,
6-[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-4-trifluoromethoxyphenyl)-N-ethylamino]-4,4-dimethylhexanoic acid hydrochloride, 6-[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-4-trifluoromethylphenyl)-N-ethylamino]-4,4-dimethylhexanoic acid hydrochloride, trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methy1}-4-
trifluoromethylphenyl)-N-ethylaraino]methyl}cyclohexyl)acetic acid hydrochloride,
trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetra zol-5-y1)amino]methyl}-4-trifluoromethoxyphenyl)-N-
ethylamino]methyl}cyclohexyl)methanol hydrochloride, 6-[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}indan-5-yl)-N-ethylamino]-5,5-dimethylhexanoic acid hydrochloride.

trans-4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-4-trifluoromethoxyphenyl)-N-
propylamino]methyl}cyclohexanecarboxylic acid hydrochloride, trans-4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-niethyl-2H-tetra2ol-5-yl) amino] methyl}-4-trifluoromethoxyphenyl)-N-
isobutylamino]methyl}cyclohexanecarboxylic acid hydrochloride, trans-4-{[N-(2-{[N"-[3,5-bis(trifluororaethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl) ainino]methyl }-4-trif luoromethoxyphenyl) -N-
ethylamino]methyl}cyclohexanecarboxylie acid amide, trans-4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)aminojmethyl1-4-trif luoromethoxyphenyl) -N-
ethylamino]methyljcyclohexanecarboxylie acid methylamide, trans-4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-y1)amino]methyl}-4-trifluoromethoxyphenyl)-N-
ethylamino]methyl}cyclohexanecarboxylic acid dimethylamide, trans-4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(4-chlorophenyl)amino]methyl}-4-trifluoromethoxyphenyl)-N-ethylaraino]methyl}cyclohexanecarboxylie acid hydrochloride, trans-4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(p-tolyl)amino]methyl}-4-trifluoromethoxyphenyl)-N-ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride, trans-4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(m-tolyl)amino]methyl}-4-trifluoromethoxyphenyl)-N-ethylamino]methyl}cyclohexanecarboxylie acid hydrochloride, trans-4-{[N-(2-{[N"-(3,5-dichlorobenzyl)-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-4-trifluoromethoxyphenyl)-N-ethylamino]methyl}cyelohexanecarboxylie acid hydrochloride, trans-4-{[N-ethyl-N-(2-{[N"-{2-methyl-2H-tetrazol-5-yl)-N"-(3-

methyl-5-trifluoromethylbenzyl)amino]methyl}-4-
trif luoromethoxyphenyl) eimino]methyl }cyclohexanecarboxylic acid
hydrochloride,
trans-4-{(N-(2-{[N"-(3-chloro-5-trifluoromethylbenzyl)-N"-(2-
methyl-2H-tetra2ol-5-yl)amino]methyl}-4-
trifluoromethoxyphenyl)-N-
ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride,
trans-4-{[N-ethyl-N-(2-{[N"-(2-methyl-2H-tetrazol-5-yl)-N"-(3-
nitro-5-trifluoromethylbenzyl)amino]methyl}-4-
trifluoromethoxyphenyl)amino]methyl}cyclohexanecarboxylie acid
hydrochloride,
trans-(4-{[N- (6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
methyl-2H-tetrazol-5-yl)amino]methyl)-2,2-
difluorobenzo[1,3]dioxol-5-yl)-N-
ethylamino]methyl}cyclohexyl)methanol hydrochloride,
trans-(4-{[N-(6-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
methyl-2H-tetrazol-5-yl)amino]methyl}-2,2-
difluorobenzo[1,3]dioxol-5-yl) -N-
ethylamino]methyl)cyclohexyl)acetic acid hydrochloride,
trans-3-(4-{[N- (2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
methyl-2H-tetrazol-5-y1)amino]methyl}-4-
trifluoromethoxyphenyl)-N-
ethylamino]methyl}cyclohexyl)propionic acid hydrochloride,
trans-(4-{[N-(7-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
raethyl-2H-tetrazol-5-yl) amino]methyl}-2,2,3,3-tetrafluoro-2,3-
dihydrobenzo[1,4]dioxin-6-yl) -N-
ethylamino]methyl)cyclohexyl)methanol hydrochloride,
trans-(4-{[N-(7-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
methyl-2H-tetrazol-5-yl)amino]methyl}-2,2,3,3-tetrafluoro-2,3-
dihydrobenzo[l,4]dioxin-6-yl)-N-
ethylamino]methyl)cyclohexyl)acetic acid hydrochloride,
trans-2-(4-{[N-(7-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
methyl-2H-tetrazol-5-yl)amino]methyl}-2,2,3,3-tetrafluoro-2,3-

dihydrobenzo[1,4]dioxin-6-y1)-N-
ethyIcimino ] methyl} cyclohexy 1) acetamide hydrochloride, trans-N-[3,5-bis(trifluoromethyl)benzyl]-N-{2-[N"-ethyl-N"-(4-(methoxymethyl)cyclohexylmethyl)amino]-5-trifluoromethoxybenzyl}-(2-methyl-2H-tetrazol-5-yl)amine hydrochloride,
trans-2-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-4-
trifluoromethoxyphenyl)-N-ethylaraino]methyllcyclohexyl)ethanol hydrochloride,
trans-(4-{[N-(2-{tN"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-4-methyl-5-trifluoromethylphenyl)-N-ethylamino]methyl}cyclohexyl)methanol hydrochloride,
trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-raethyl-2H-tetrazol-5-yl)amino]methyl}-5-methyl-4-trifluoromethylphenyl)-N-ethylamino]methyl}cyclohexy1)acetic acid hydrochloride,
trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-4-methyl-5-trifluoromethylphenyl)-N-ethylaraino]methyl}cyclohexyl)acetic acid hydrochloride,
trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl)-4-trifluoromethoxyphenyl)-N-
ethylamino]methyl)cyclohexylmethyl)phosphonic acid, trans-4-{[N-{2-{[N"-(3-bromo-5-trifluoromethylbenzyl)-N"-(2-methyl-2H-tetrazol-5-yl)amino]raethyl)-4-trifluoromethoxyphenyl)-N-
ethyleimino]methyl)cyclohexanecarboxylic acid hydrochloride, trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl)-4-bromophenyl)-N-ethylamino]methyl)cyclohexyl)methanol hydrochloride.

trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-inethyl-2H-tetrazol-5-yl)amino]methyl}-4-bromophenyl)-N-ethylcunino]methyl}cyclohexyl)acetic acid hydrochloride, trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetra2ol-5-yl)amino]methyl}-4-chloro-5-ethylphenyl) -N-ethylamino]methyl}cyclohexyl)methanol hydrochloride, trans-4-{[N-(2-{tN"-[3,5-bis(trifluoromethyl)benzyl]-N"-(4-methoxyphenyl)amino]methyl1-4-trifluoromethoxyphenyl)-N-ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride, trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-5-methoxy-4-methylphenyl) -N-ethylcunino] methyl} cyclohexyl) methanol hydrochloride,
trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-4,5-dimethylphenyl)-N-ethylamino]methyl)cyclohexyl)acetic acid hydrochloride, trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl)-4-trifluoromethylthiophenyl)-N-
ethylamino]methyl)cyclohexyl)acetic acid hydrochloride, trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-raethyl-2H-tetrazol-5-yl)amino]methyl}-4-chloro-5-ethylphenyl) -N-ethylamino]methyl)cyclohexyl)acetic acid hydrochloride, trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-4-
trifluoromethylphenyl)-N-propylamino]methyl)cyclohexyl)acetic acid hydrochloride,
trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-5-methoxy-4-methylphenyl)-N-ethylamino]methyl}cyclohexyl)acetic acid hydrochloride,
trans-4-({N-[2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-4-(2,2,2-

trifluoroethyl)phenyl]-N-
ethylamino}methyl)cyclohexanecarboxylie acid hydrochloride,
trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
raethyl-2H-tetra2ol-5-yl)amino]methyl}-5-methyl-4-
trifluoromethylphenyl)-N-propylamino]methyl}cyclohexyl)acetic
acid hydrochloride,
trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
methyl-2H-tetra2ol-5-yl)amino]methyl}-4-
trifluoromethoxyphenyl)-N-propylaraino]methyl}cyclohexyl)acetic
acid hydrochloride,
trans-4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(4-
ethylphenyl)amino]methyl}-4-trifluoromethoxyphenyl)-N-
ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride,
trans-4-{[N-(2-{[N"-(3-cyano-5-trifluoromethylbenzyl)-N"-(2-
methyl-2H-tetrazol-5-yl)amino]methyl}-4-
trifluoromethoxyphenyl)-N-
ethylamino]methyl}cyclohexanecarboxylic acid hydrochloride,
trans-4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(4-
isopropenylphenyl)amino]methyl}-4-trifluoromethoxyphenyl)-N-
ethylamino]methyl}cyclohexanecarboxylic acid,
trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(p-
tolyl)amino]methyl)-4-trifluoromethoxyphenyl)-N-
ethylamino]methyl}cyclohexyl)acetic acid dihydrochloride,
trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(5-
methyl-[1,2,4]oxadiazol-3-yl)amino]methyl}-4-
trifluoromethoxyphenyl)-N-ethylamino]methyl}cyclohexyl)acetic
acid hydrochloride,
trans-(4-{[N- (2-{ [N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(5-
methyl-[1,2,4]oxadiazol-3-yl)amino]methyl}-5-methyl-4-
trifluoromethylphenyl)-N-ethylamino]methyl}cyclohexyl)acetic
acid hydrochloride,
trans-(4-{[N- (2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(5-
methyl-[1,2,4]oxadiazol-3-yl)amino]methyl}-5-methyl-4-

trifluoromethylphenyl)-N-propylamino]methyl}cyclohexyl)acetic
acid hydrochloride,
trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
methyl-2H-tetrazol-5-yl)amino]methyl}-5-methyl-4-
trifluoromethylphenyl)-N-propylamino]methyl}cyclohexyl)acetic
acid,
trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
methyl-2H-tetrazol-5-yl)amino]methyl}-4-methyl-5-
trifluoromethylphenyl)-N-ethylamino]methyl}cyclohexyl)acetic
acid,
trans-(4-{[N-(2-{[N"-[3,5-bi3(trifluoromethyl)benzyl]-N"-(2-
raethyl-2H-tetrazol-5-yl)amino]methyl}-5-methyl-4-
trifluoromethylphenyl)-N-ethylamino]methyl}cyclohexyl)acetic
acid methanesulfonate,
ethyl trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-
N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-5-methyl-4-
trifluoromethylphenyl)-N-ethylamino]methyl}cyclohexyl)acetate
and
trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
methyl-2H-tetrazol-5-yl)amino]methyl}-5-methyl-4-
trifluoromethylphenyl)-N-ethylamino]methyl}cyclohexyl)acetic
acid
or a prodrug thereof or a pharmaceutically acceptable salt
thereof,
12. The dibenzylamine compound as claimed in claim 1, which is selected
from the group consisting of
trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
methyl-2H-tetrazol-5-yl)amino]methyl)-4-
trifluoromethoxyphenyl)-N-ethylamino]methyl)cyclohexyl)acetic
acid hydrochloride,
trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-
methyl-2H-tetrazol-5-yl)amino]methyl}-4-

trifluoromethylphenyl)-N-ethylamino]methyl}cyclohexyl)acetic acid hydrochloride,
trans-(4-{[N-(2-{ [N"-[3,5-bis(trifluoromethyl)ben2yl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-5-methyl-4-trifluoromethylphenyl)-N-ethylamino]methyl}cyclohexyl)acetic acid hydrochloride,
trans-(4-{[N-{2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-4-methyl-5-trifluoromethylphenyl)-N-ethylamino]methyl}cyclohexyl)acetic acid hydrochloride,
trans-(4-{[N-(2-{ [N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-4-
trifluoromethylphenyl)-N-propylamino]methyl}cyclohexyl)acetic acid hydrochloride,
trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-5-methyl-4-trifluoromethylphenyl)-N-propylamino]methyl}cyclohexyl)acetic acid hydrochloride,
trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-4-
trifluororaethoxyphenyl)-N-propylamino]methyl}cyclohexyl)acetic acid hydrochloride,
trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-5-methyl-4-trifluoromethylphenyl)-N-propylamino]methyl}cyclohexyl)acetic acid,
trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-4-methyl-5-trif luoromethylphenyl) -N-ethylamino]methyl}cyclohexyl)acetic acid and
trans-(4-{[N-(2-{[N"-[3,5-bis(trifluoromethyl)benzyl]-N"-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-5-methyl-4-trifluoromethylphenyl)-N-ethylamino]methyl}cyclohexyl)acetic

acid methanesulfonate
or a prodrug thereof or a pharmaceutically acceptable salt
thereof.
13. The dibenzylamine compound as claimed in claim 2, which is selected from the group consisting of
N-[3-(N"-cyclopentylmethyl-N"-ethylamino)-5,6,7,8-tetrahydronaphthalen-2-ylmethyl]-N-[3,5-
bis(trifluoromethyl)benzyl]-(2-methyl-2H-tetrazol-5-yl)amine, 3-{[N-[3-(N"-cyclopentylmethyl-N"-ethylamino)-5,6,7,8-tetrahydronaphthalen-2-ylmethyl]-N-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-5-trifluoromethylbenzonitrile, N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-(2-methyl-2H-tetrazol-5-yl)amine,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentyImethyl-N"-ethylamino)indan-5-ylmethyl]-(2-methyl-2H-tetrazol-5-yl)amine hydrochloride,
N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-N-(2H-tetrazol-5-yl)-[3,5-bis(trifluoromethyl)benzyl]amine, N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-N-[3,5-bis(trifluoromethyl)benzyl]-(pyrimidin-2-yl)amine hydrochloride,
N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-N-[3,5-bis(trifluoromethyl)benzyl]-(5-methyl-lH-pyrazol-3-yl)amine,
3-{[N-16-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-N-(2-methyl-2H-tetrazol-5-yl)amino]methyl}-5-trifluoromethylbenzonitrile,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentyImethyl-N"-ethylamino)indan-5-ylmethyl]-(2-ethyl-2H-tetrazol-5-yl)amine, N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentyImethyl-

N"-ethylamino)indan-5-ylmethyl]-(1-methyl-lH-[1,2,4]triazol-3-yl) amine,
3-({N-[6-(N"-cyclopentylmethy1-N"-ethylamino)indan-5-ylmethyl]-N-phenylamino}methyl)-5-trifluoromethylbenzonitrile, 3-{[N-[6-(N"-cyclopentylmethy1-N"-ethylamino)indan-5-ylmethyl]-N-(4,5-dimethyl-thiazol-2-yl) amino]methyl}-5-trifluoromethylbenzonitrile,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino) indan-5-ylmethyl]-(thiazol-2-yl)amine hydrochloride,
3-({N-[6-(N"-cyclopentylmethy1-N"-ethylamino)indan-5-ylmethylJ-N-(thiazol-2-yl)amino}methyl)-5-trifluoromethylbenzonitrile hydrochloride,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylraethyl-N"-ethylamino)indan-5-ylmethyl]-(oxazol-2-yl)amine hydrochloride,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-(5-methylthiazol-2-yl)amine hydrochloride,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-(4-methylthiazol-2-yl)amine hydrochloride,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-(4,5-dimethylthiazol-2-yl)amine hydrochloride,
3-{[N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-N-(5-methylthiazol-2-yl)amino]methyl}-5-trifluoromethylbenzonitrile hydrochloride, 3-{[N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-N-{4-methylthiazol-2-yl)amino]methyl)-5-trifluoromethylbenzonitrile hydrochloride,
N-t3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-(4-methyloxazol-2-yl)amine

hydrochloride,
N-[3,5-bis(trifluoromethy1)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-(3-methylisothiazol-5-yl)amine hydrochloride,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino) indan-5-ylmethyl] - {5-niethylisoxazol-3-yl) amine hydrochloride,
N-[3,5-bis(trifluorpmethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-(3-methylisoxazol-5-yl)amine hydrochloride,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino) indan-5-ylmethyl]-(l-methyl-lH-pyrazol-3-yl)amine hydrochloride,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino) indan-5-ylmethyl]-(l-methyl-lH-pyrazol-4-yl)amine hydrochloride,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-(5-methyl-[1,3,4]thiadiazol-2-yl)amine hydrochloride,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-(5-methyl-[1,3,4]oxadiazol-2-yl)amine hydrochloride,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylcimino) indan-5-ylmethyl] -pyridin-3-ylamine hydrochloride,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[6-(N"-cyclopentylmethyl-N"-ethylamino)indan-5-ylmethyl]-pyridin-2-ylamine hydrochloride,
N-[3,5-bis(trifluoromethyl)benzyl]-N-[2-(N"-cyclopentylmethyl-N"-ethylamino) -5-trifluoromethylbenzyl]-(2-raethyl-2H-tetrazol-5-yl)amine hydrochloride and
3-{[N-[2-(N"-cyclopentylmethyl-N"-ethylamino)-5-trifluoromethylbenzyl]-N-(2-methyl-2H-tetrazol-5-

yl) amino]methyl}-5-trifluorpmethylbenzonitrile hydrochloride or a prodrug thereof or a pharmaceutically acceptable salt thereof.
14. A pharmaceutical composition comprising the diben^ylamine compound of any of claims 1 to 13 or a prodrug thereoff or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
15. A CETP activity inhibitor comprising a dibenzyleunine compound of any of claims 1 to 13 or a prodrug thereof or a pharmaceutically acceptable salt thereof as an active ingredient.
16. A therapeutic agent or a prophylactic agent for hyperlipidemia, which comprises a dibenzylamine compound of any of claims 1 to 13 or a prodrug thereof or a pharmaceutically acceptable salt thereof as an active ingredient.

17. A therapeutic agent or a prophylactic agent for arteriosclerosis, which comprises a dibenzylamine compound of any of claims 1 to 13 or a prodrug thereof or a pharmaceutically acceptable salt thereof as an active ingredient.
18. The pharmaceutical composition as claimed in claim 14, which is used in combination with a different therapeutic agent for hyperlipidemia.

19. The pharmaceutical composition as claimed in claim 18, wherein the different therapeutic agent for hyperlipidemia is a statlin pharmaceutical agent.
20. The pharmaceutical composition as claimed in claim 19, wherein the statin pharmaceutical agent is at least one pharmaceutical agent selected from the group consisting of lovastatin, simvastatin, pravastatin, fluvastatin, atorvastatin and cerivastatin,
21. The pharmaceutical composition as claimed in claim 14, which is used in combination with a different therapeutic agent for obesity.

22. The pharmaceutical composition as claimed in claim 21, wherein the different therapeutic agent for obesity is mazindol.
23. The pharmaceutical composition as claimed in claim 14, which is used in combination with a different therapeutic agent for diabetes.
24. The pharmaceutical composition as claimed in claim 23, wherein the different therapeutic agent for diabetes is at least one pharmaceutical agent selected from the group consisting of an insulin preparation, a sulfonylurea, an insulin secretagogue, a sulfonamide, a biguanide, an a glucosidase inhibitor and an insulin sensitizer.

25. The pharmaceutical composition as claimed in claim 24, wherein the different therapeutic agent for diabetes is at least one pharmaceutical agent selected from the group consisting of insulin, glibenclamide, tolbutamide, glyclopyramide, acetohexamide, glimepiride, tolazamide, gliclazide, nateglinide, glybuzole, metformin hydrochloride, buformin hydrochloride, voglibose, acarbose and pioglitazone hydrochloride.
26. The pharmaceutical composition as claimed in claim 14, which is used in combination with a different therapeutic agent for hypertension.
27. The pharmaceutical composition as claimed in claim 26, wherein the different therapeutic agent for hypertension is at least one pharmaceutical agent selected from the group consisting of a loop diuretic, an angiotensin converting enzyme inhibitor, an angiotensin II receptor antagonist, a Ca antagonist, a p blocker, an a^p blocker and an a blocker.
28. The pharmaceutical composition as claimed in claim 27, wherein the different therapeutic agent for hypertension is at least one pharmaceutical agent selected from the group consisting of a

captopril sustained-release preparation, enalapril maleate, alacepril, delapril hydrochloride, cilazapril, lisinopril, benazepril hydrochloride, imidapril hydrochloride, teraocapril hydrochloride, quinapril hydrochloride, trandrap|ril, perindopril erbxmiine, losartan potassium, candes^rtan cilexetil, nicardipine hydrochloride, a nicardipitne hydrochloride sustained-release preparation, nilVadipine, nifedipine, a nifedipine sustained-release prepafcation, benidipine hydrochloride, diltiazem hydrochloridie, a diltiazem hydrochloride sustained-release preparation, nisoidipine, nitrendipine, manidipine hydrochloride, barnidifline hydrochloride, efonidipine hydrochloride, amlodilpine besylate, felodipine, cilnidipine, aranidipine, propranolol hydrochloride, a propranolol hydrochloride sustained-release preparation, pindolol, a pindolol sustained-release preparation, indenolol hydrochloride, carteolol hydrochloride, a carteolol hydrochloride sustained-release preparatipn, bunitrolol hydrochloride, a bunitrolol hydrochloride sustained-release preparation, atenolol, acebutolol hydrochloride, metoprolol tartrate, a metoprolol tartrate sustained-release preparation, nipradilol, penbutolol sulfate, tilisolol hydrochloride, carvedilol, bisoprolol furaarate, betaxolol hydrochloride, celiprolol hydrochloride, bopindolol malonate, bevantolol hydrochloride, labetalol hydrochloride, arotinolol hydrochloride, amosulalol hydrochloride, prazosin hydrochloride, terazosin hydrochloride, doxazosin mesylate, bunazosin hydrochloride, a bunazosin hydrochloride sustained-release preparation, urapidil and phentolamine mesylate.
29. The therapeutic agent or a prophylactic agent as claimed in claim 16, which aims at the treatment or prophylaxis of hyperlipidemia and which is used in combination with a different therapeutic

agent for hyperlipidemia.
30. The therapeutic agent or a prophylactic agent as claimed in claim 29,
wherein the different therapeutic agent for hyperlipidemia is a statin pharmaceutical agent.
31. The therapeutic agent or a prophylactic agent as claimed in claim 30,
wherein the statin pharmaceutical agent is at lea^t one
pharmaceutical agent selected from the group consisting of
lovastatin, simvastatin, pravastatin, fluvastatih,
atorvastatin and cerivastatin.
32. The therapeutic agent or a prophylactic agent as claimed in claim 16, which aims at the treatment or prophylaxis of Hyperlipidemia and which is used in combination with a different therapeutic agent for obesity.
33. The therapeutic agent or a prophylactic agent as claimed in claim 32, wherein the different therapeutic agent for obesity is
mazindol.
34. The therapeutic agent or a prophylactic agent as claimed in claim 16, which aims at the treatment or prophylaxis of hyperlipideipia and which is used in combination with a different therapeutic agent for diabetes.
35. The therapeutic agent or a prophylactic agent as claimed in claim 34, wherein the different therapeutic agent for diabetes is at least one pharmaceutical agent selected from the group consisting of an insulin preparation, a sulfonylurea, an insulin secretagogue, a sulfonamide, a biguanide, an a glucosidase inhibitor and an insulin sensitizer.

36. The therapeutic agent or a prophylactic agent as claimed in claim 35,
wherein the different therapeutic agent for diabetes is at least one pharmaceutical agent selected from the group . consisting of insulin, glibenclamide, tolbutamide, glyclopyramide, acetohexamide, glimepiride, tolazamide, gliclazide, nateglinide, glybuzole, metformin hydrochloridte, bufoirmin hydrochloride, voglibose, acarbose and pioglitazqne hydrochloride.
37. The therapeutic agent or a prophylactic agent as claimed in claim 16, which aims at the treatment or prophylaxis of hyperlipidemia and which is used in combination with a different therapeutic agent for hypertension.
38. The therapeutic agent or a prophylactic agent as claimed in claim 37, wherein the different therapeutic agent for hypertension is at least one pharmaceutical agent selected from the group consisting of a loop diuretic, an angiotensin converting enzyme inhibitor, an angiotensin II receptor antagonist, a Ca antagonist, a p blocker, an a^P blocker and an a blocker.
39. The therapeutic agent or a prophylactic agent as claimed in claim 38, wherein the different therapeutic agent for hypertension is at least one pharmaceutical agent selected from the group consisting of a furosemide sustained-release preparation, a captopril, captopril sustained-release preparation, enalapril maleate, alacepril, delapril hydrochloride, cilazapril, lisinopril, benazepril hydrochloride, imidapril hydrochloride, temocapril hydrochloride, quinapril hydrochloride, trandrapril, perindopril erbumine, losartan potassium, candesartan cilexetil, nicardipine hydrochloride, a nicardipine hydrochloride sustained-release preparation, nilvadipine, nifedipine, a nifedipine sustained-release preparation,

benidipine hydrochloride, diltiazem hydrochloride, a diltiazem hydrochloride sustained-release preparation, nisoldipine, nitrendipine, manidipine hydrochloride, barnidipine hydrochloride, efonidipine hydrochloride, amlodipine besylate, felodipine, cilnidipine, aranidipine, propranolol hydrochloride, a propranolol hydrochloride sustained-release preparation, pindolol, a pindolol sustained-release preparation, indenolol hydrochloride, carteolol hydrochloride, a carteolol hydrochloride sustained-release preparation, bunitrolol hydrochloride, a bunitrolol hydrochloride sustained-release preparation, atenolol, acebutolol hydrochloride, metoprolol tartrate, a metoprolol tartrate sustained-release preparation, nipradilol, penbutolol sulfate, tilisolol hydrochloride, carvedilol, bisoprolol fuinarate, betaxolol hydrochloride, celiprolol hydrochloride, bopindolol malonate, bevantolol hydrochloride, labetalol hydrochloride, arotinolol hydrochloride, amosulalol hydrochloride, prazosin hydrochloride, terazosin hydrochloride, doxazosin mesylate, bunazosin hydrochloride, a bunazosin hydrochloride sustained-release preparation, urapidil and phentolamine mesylate.
40. The therapeutic agent or a prophylactic agent as claimed in claim 17, which aims at the treatment or prophylaxis of arteriosclerosis and which is used in combination with a different therapeutic agent for hyperlipidemia.
41. The therapeutic agent or a prophylactic agent as claimed in claim 40, wherein the different therapeutic agent for hyperlipidemia is a statin phainnaceutical agent.

42. The therapeutic agent or a prophylactic agent as claimed in claim 41,
wherein the statin pharmaceutical agent is at least one
pharmaceutical agent selected from the group consisting of
lovastatin, simvastatin, pravastatin, fluvastatin,
atorvastatin and cerivastatin.
43. The therapeutic agent or a prophylactic agent as claimed in claim 17,
which aims at the treatment or prophylaxis of arteriosclerosis
and which is used in combination with a different therapeutic
agent for obesity.
44. The therapeutic agent or a prophylactic agent as claimed in claim 43, wherein the different therapeutic agent for obesity is mazindol.
45. The therapeutic agent or a prophylactic agent as claimed in claim 17, which aims at the treatment or prophylaxis of arteriosclerosis and which is used in combination with a different therapeutic agent for diabetes.
46. The therapeutic agent or a prophylactic agent as claimed in claim 45, wherein the different therapeutic agent for diabetes is at least one pharmaceutical agent selected from the group consisting of an insulin preparation", a sulfonylurea, an insulin secretagogue, a sulfonamide, a biguanide, an a glucosidase inhibitor and an insulin sensitizer.

47. The therapeutic agent or a prophylactic agent as claimed in claim 46, wherein the different therapeutic agent for diabetes is at least one pharmaceutical agent selected from the group consisting of insulin, glibenclamide, tolbutamide, glyclopyramide, acetohexamide, glimepiride, tolazamide, gliclazide, nateglinide, glybuzole, metformin hydrochloride, buformin hydrochloride, voglibose, acarbose and pioglitazone hydrochloride.
48. The therapeutic agent or a prophylactic agent as claimed in claim 17, which aims at the treatment or prophylaxis of arteriosclerosis and which is used in combination with a different therapeutic agent for hypertension.
49. The therapeutic agent or a prophylactic agent as claimed in claim 48, wherein the different therapeutic agent for hypertension is at least one pharmaceutical agent selected from the group consisting of a loop diuretic, an angiotensin converting enzyme inhibitor, an angiotensin II receptor antagonist, a Ca antagonist, a p blocker, an a^P blocker and an a blocker.
50. The therapeutic agent or a prophylactic agent as claimed in claim 49, wherein the different therapeutic agent for hypertension is at least one pharmaceutical agent selected from the group consisting of a furosemide sustained-release preparation, captopril, a captopril sustained-release preparation.

enalapril maleate, alacepril, delapril hydrochloride, cilazapril, lisinopril, benazepril hydrochloride, iraidapril hydrochloride, temocapril hydrochloride, quinapril hydrochloride, trandrapril, perindopril erbumine, losartan potassium, candesartan cilexetil, nicardipine hydrochloride, a nicardipine hydrochloride sustained-release preparation, nilvadipine, nifedipine, a nifedipine sustained-release preparation, benidipine hydrochloride, diltiazera hydrochloride, a diltiazem hydrochloride sustained-release preparation, nisoldipine, nitrendipine, manidipine hydrochloride, barnidipine hydrochloride, efonidipine hydrochloride, amlodipine besylate, felodipine, cilnidipine, aranidipine, propranolol hydrochloride, a propranolol hydrochloride sustained-release preparation, pindolol, a pindolol sustained-release preparation, indenolol hydrochloride, carteolol hydrochloride, a carteolol hydrochloride sustained-release preparation, bunitrolol hydrochloride, a bunitrolol hydrochloride sustained-release preparation, atenolol, acebutolol hydrochloride, metoprolol tartrate, a metoprolol tartrate sustained-release preparation, nipradilol, penbutolol sulfate, tilisolol hydrochloride, carvedilol, bisoprolol fvimarate, betaxolol hydrochloride, celiprolol hydrochloride, bopindolol malonate, bevantolol hydrochloride, labetalol hydrochloride, arotinolol hydrochloride, amosulalol hydrochloride, prazosin hydrochloride, terazosin hydrochloride, doxazosin mesylate, bunazosin hydrochloride, a bunazosin hydrochloride sustained-release preparation, urapidil and phentolamine mesylate.

Documents:

0889-chenp-2004 abstract-duplicate.pdf

0889-chenp-2004 abstract.pdf

0889-chenp-2004 claims-duplicate.pdf

0889-chenp-2004 claims.pdf

0889-chenp-2004 correspondences-others.pdf

0889-chenp-2004 correspondences-po.pdf

0889-chenp-2004 description (complete)-1.pdf

0889-chenp-2004 description (complete)-2.pdf

0889-chenp-2004 description (complete)-duplicate-1.pdf

0889-chenp-2004 description (complete)-duplicate-2.pdf

0889-chenp-2004 form-1.pdf

0889-chenp-2004 form-19.pdf

0889-chenp-2004 form-26.pdf

0889-chenp-2004 form-3.pdf

0889-chenp-2004 form-5.pdf

0889-chenp-2004 others document.pdf

0889-chenp-2004 pct.pdf

889-chenp-2004.jpg


Patent Number 214358
Indian Patent Application Number 889/CHENP/2004
PG Journal Number 13/2008
Publication Date 31-Mar-2008
Grant Date 11-Feb-2008
Date of Filing 28-Apr-2004
Name of Patentee JAPAN TOBACCO INC
Applicant Address 2-1, Toranomon 2-chome, Minato-ku, Tokyo 105-8422,
Inventors:
# Inventor's Name Inventor's Address
1 MAEDA, Kimiya c/o Central Pharmaceutical Research Institute of Japan Tobacco Inc., 1-1, Murasaki-cho, Takatsuki-shi, Osaka 569-1125,
2 NAGAMORI, Hironobu c/o Central Pharmaceutical Research Institute of Japan Tobacco Inc., 1-1, Murasaki-cho, Takatsuki-shi, Osaka 569-1125,
3 NAKAMURA, Hiroshi c/o Central Pharmaceutical Research Institute of Japan Tobacco Inc., 1-1, Murasaki-cho, Takatsuki-shi, Osaka 569-1125,
4 SHINKAI, Hisashi c/o Central Pharmaceutical Research Institute of Japan Tobacco Inc., 1-1, Murasaki-cho, Takatsuki-shi, Osaka 569-1125,
5 SUZUKI, Yasunori c/o Central Pharmaceutical Research Institute of Japan Tobacco Inc., 1-1, Murasaki-cho, Takatsuki-shi, Osaka 569-1125,
6 TANIGUCHI, Toshio c/o Central Pharmaceutical Research Institute of Japan Tobacco Inc., 1-1, Murasaki-cho, Takatsuki-shi, Osaka 569-1125,
7 TAKAHASHI, Daisuke c/o Central Pharmaceutical Research Institute of Japan Tobacco Inc., 1-1, Murasaki-cho, Takatsuki-shi, Osaka 569-1125,
PCT International Classification Number C07C 229/46
PCT International Application Number PCT/JP2003/011041
PCT International Filing date 2003-08-29
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 2003-107161 2003-04-10 Japan
2 2002-255604 2002-08-30 Japan