Title of Invention

"DERIVATIVES OF PIPERIDINYLALKYLCARBAMATES, PREPARATION METHOD THEREOF AND USE OF SAME AS FAAH ENZYME INHIBITORS"

Abstract Derivatives of piperidinyl alkyl carbamates, preparation method thereof on use of same as FAAH enzyme inhibitors The invention relates to a compound having general formula (I), wherein: m - 1 to 4; n represents =1, 2 or 3; o = 1 or 2; A is selected from among one or more X, Y and/or Z groups; X optionally-substituted methylene; Y = C2-alkenylene, optionally substituted; Z = C3-7-cycloalkyl; B = covalent bond or C1-6-alkylene; G = covalent bond, O, S, -CH(OH)-, CO, SO or SO2; R1 represents an aryl- or heteroaryl-type group; R2 = hydrogen or C1-6-alkyl; R3 = hydrogen, C1-6-alkyl, C3-7-cycloalkyl, C3-7-cycloalkyl-C1-3-alkylene. The inventive compound takes the form of a base, an acid addition salt, a hydrate or a solvate. Said compound is suitable for use as FAAH enzyme inhibitors.
Full Text The invention relates to pipendinylalkyl-
carbamate derivatives, to their preparation and to
their application in therapy.
Already known are phenylalkylcarbamate
derivatives, dioxane-2-alkylcarbamate derivatives and
piperidinyl- and piperazinyl-alkylcarbamate
derivatives, described respectively in the documents
WO 2004/067498 A, WO 2004/020430 A and WO 2004/099176,

which are inhibitors of the enzyme FAAH (fatty acid
amide hydrolase).
There is still a need to find and to develop
products which inhibit the enzyme FAAH. The compounds
of the invention meet this goal.
The compounds of the invention are of the
general formula (I)

in which
m represents an integer from 1 to 4;
n represents an integer 1, 2 or 3;
o an integer 1 or 2;
A is selected from one or more groups X, Y and/or Z;

X represents a methylene group optionally
substituted by one or two Ci-6 alkyl, C3-7 cycloalkyl
or C3.7 cycloalkyl-C1-3 alkylene groups;
Y represents either a C2 alkenylene group optionally
substituted by one or two Ci-6 alkyl, C3-7 cycloalkyl
or C3-7 cycloalkyl-C1-3 alkylene groups, or a C2
alkynylene group;
Z represents a group of formula:

p represents an integer from 1 to 5;
q and r represent integers and are defined such
that r+q is a number from 1 to 5;
B represents a covalent bond or a Ci-6 alkylene group;
G represents a covalent bond, an oxygen or sulphur
atom or a -CH(OH)-, CO, SO or S02 group;
Ri represents a group R4 optionally substituted by one
or more groups R5 and/or R6;
R4 represents a group selected from a furanyl,
pyrrolyl, thienyl, oxazolyl, isoxazolyl, thiazolyl,
isothiazolyl, imidazolyl, pyrazolyl, thiadiazolyl,
isothiadiazolyl, oxadiazolyl, thiadiazolyl,
triazolyl, tetrazolyl, phenyl, pyridinyl,
pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl,
naphthalenyl, quinolinyl, tetrahydroquinolinyl,
isoquinolinyl, tetrahydroisoquinolinyl,
phthalazinyl, quinazolinyl, quinoxalinyl,

cinnolinyl, naphthyridinyl, imidazopyrimidinyl,
thienopyrimidinyl, benzofuranyl, dihydrobenzo-
furanyl, benzothienyl, dihydrobenzothienyl,
benzimidazolyl, benzoxazolyl, benzisoxazolyl,
benzothiazolyl, benzisothiazolyl, indolyl,
isoindolyl, indazolyl, pyrrolopyridinyl,
furopyridinyl, dihydrofuropyridinyl,
thienopyridinyl, dihydrothienopyridinyl,
imidazopyridinyl, pyrazolopyridinyl,
oxazolopyridinyl, isoxazolopyridinyl,
thiazolopyridinyl;
R5 represents a halogen atom, a cyano, nitro,
hydroxyl, Cx.6 alkyl, Ci-6 alkoxy, Ci_6 thioalkyl, Ci-6
fluoroalkyl, Ci-6 fluoroalkoxy, Ci-6 fluorothioalkyl,
C3.7 cycloalkyl or C3-7 cycloalkyl-Ci-3 alkylene group
or a group NR7R8, NR7COR8, NR7C02R8, NR7S02R8, COR7/
C02R7; CONR7R8, S02R7, S02NR7R8 or -0- (C1.3 alkylene) -
0-;
R6 represents a phenyl, phenyloxy, benzyloxy,
pyridinyl, pyrazinyl, pyridazinyl, pyrimidinyl or
pyrimidinyloxy group; it being possible for the
group or groups R6 to be substituted by one or more
groups R5 identical to or different from one
another;
R7 and R8 represent independently of one another a
hydrogen atom or a d-6 alkyl group, or, with the
atom or atoms which carry them, form a ring

selected from an azetidine, pyrrolidine,
piperidine, morpholine, thiomorpholine, azepine or
piperazine ring, this ring being optionally-
substituted by a Ci-s alkyl or benzyl group;
R2 represents a hydrogen atom or a Ci-6 alkyl group;
R3 represents a hydrogen atom or a Ci-6 alkyl, C3.7
cycloalkyl or C3.7 cycloalkyl-Ci-3 alkylene group.
In the context of the invention the compounds
of general formula (I) may therefore comprise two or
more groups A identical to or different from one
another.
Among the compounds of general formula (I) a
first subgroup of compounds is composed of the
compounds for which:
m represents an integer from 1 to 4;
n represents an integer 1 or 2;
o an integer 1 or 2;
A is selected from one or more groups X and/or Y;
X represents a methylene group optionally
substituted by one or two Ci-6 alkyl groups, more
particularly methyl;
Y represents a C2 alkynylene group;
B represents a covalent bond or a Ci-6 alkylene group,
more particularly a methylene or an ethylene;
G represents a covalent bond or an oxygen atom;
Ri represents a group R4 optionally substituted by one
or more groups R5 and/or R6, more particularly by

one or two groups R5 and/or R6;
R4 represents a group selected from an oxazolyl,
isoxazolyl, thiazolyl, phenyl, pyridinyl,
naphthalenyl, quinolinyl, isoquinolinyl;
R5 represents a halogen atom, more particularly a
chlorine, a bromine or a fluorine, a cyano group, a
group NR7R8, or a Ci-6 alkyl group, more particularly
a methyl or an isopropyl, a Ci-6 alkoxy group, more
particularly a methoxy or an ethoxy, a Ci-6 fluoro-
alkyl group, more particularly a trifluoromethyl,
or a Ci-6 fluoroalkoxy group, more particularly a
trifluoromethoxy;
R6 represents a phenyl, phenyloxy or pyrimidinyloxy
group; it being possible for the group or groups R6
to be substituted by one or more groups R5 identical
to or different from one another;
R7 and R8 represent independently of one another a
Ci-6 alkyl group, more particularly a methyl;
R2 represents a hydrogen atom or a Ci-6 alkyl group;
R3 represents a hydrogen atom or a Cx.6 alkyl, C3.7
cycloalkyl or C3.7 cycloalkyl-Ci-3 alkylene group.
Among the compounds of general formula (I)
and of the first subgroup, a second subgroup of
compounds is composed of the compounds for which:
n, o, A, B, G, Ri, R2 and R3 are as defined in the
formula (I) or in the subgroup above;
m represents an integer 1 or 2, more particularly 1.

Among the compounds of general formula (I)
and of the subgroups above, a third subgroup of
compounds is composed of the compounds for which:
m, A, B, G, Ri, R2 and R3 are as defined in the formula
(I) or in the subgroups above;
n is 2;
o is 2.
Among the compounds of general formula (I)
and of the subgroups above, a fourth subgroup of
compounds is composed of the compounds for which:
m, n, o, A, B, G, R2 and R3 are as defined in the
formula (I) or in the subgroups above;
Rx represents a group R4 optionally substituted by one
or more groups R5 and/or R6/ more particularly by one or
two groups R5 and/or R6;
R4 represents a group selected from an oxazolyl,
isoxazolyl, phenyl or naphthalenyl;
R5 represents a halogen atom, more particularly a
chlorine, a bromine or a fluorine, a cyano group, a
group NR7R8, a Ci-6 alkyl group, more particularly a
methyl or an isopropyl, a Cx.6 alkoxy group, more
particularly a methoxy or an ethoxy, a Ci-6 fluoro-
alkyl group, more particularly a trifluoromethyl,
or a Ci-6 fluoroalkoxy group, more particularly a
trifluoromethoxy;
R6 represents a phenyl, phenyloxy or pyrimidinyloxy
group; it being possible for the group or groups R6

to be substituted by one or more groups R5 identical
to or different from one another;
R7 and RQ represent independently of one another a
Ci-6 alkyl group, more particularly a methyl.
Among the compounds of general formula (I) a
fifth subgroup of compounds is composed of the
compounds for which:
m, n, o, A, B, G, and Ri are as defined in the formula
(I) or in the subgroups above;
R2 represents a hydrogen atom;
R3 represents a hydrogen atom or a Ci-6 alkyl group, more
particularly a methyl.
Among the compounds of general formula (I)
mention may be made of the following compounds:
- 2-(methylamino)-2-oxoethyl {l-[(3,4'-difluorobi-
phenyl-4-yl)methyl]piperidin-4-yl}methylcarbamate;
- 2-(methylamino)-2-oxoethyl {l-[(3-chloro-4'-fluorobi-
phenyl-4-yl)methyl]piperidin-4-yl}methylcarbamate;
- 2-(methylamino)-2-oxoethyl {l-[3-(4-fluorophenoxy)-
benzyl]piperidin-4-yl}methylcarbamate;
- 2-(methylamino)-2-oxoethyl {l-[4-(4-chloro-3-fluoro-
phenoxy) benzyl]piperidin-4-yl}methylcarbamate;
- 2-(methylamino)-2-oxoethyl 2-{l-[3-(trifluoro-
methoxy)benzyl]piperidin-4-yl}ethylcarbamate;
- 2-(methylamino)-2-oxoethyl 2-{l-[4-(trifluoro-
methoxy)benzyl]piperidin-4-yl}ethylcarbamate;
- 2-(methylamino)-2-oxoethyl 2-[1-(3-tert-butoxy-

benzyl)piperidin-4-yl]ethylcarbamate;
- 2-(methylamino)-2-oxoethyl 2-[1-(3-tert-butoxy-
benzyDpiperidin^-yljmethylcarbamate;
- 2-(methylamino)-2-oxoethyl 2-[1-(2,4-dichloro-
benzyl)piperidin-4-yl]ethylcarbamate;
- 2-(methylamino)-2-oxoethyl 2-[1-(2,5-dichloro-
benzyl)piperidin-4-yl]ethylcarbamate;
- 2-(methylamino)-2-oxoethyl 2-[1-(3,5-dichloro-
benzyl)piperidin-4-yl]ethylcarbamate;
- 2-(methylamino)-2-oxoethyl 2-[1-(2-chloro-5-fluoro-
benzyl)piperidin-4-yl]ethylcarbamate;
- 2-(methylamino)-2-oxoethyl 2-[1-(3-chloro-2-fluoro-
benzyl)piperidin-4-yl]ethylcarbamate;
- 2-(methylamino)-2-oxoethyl 2-[1-(3-chloro-5-methyl-
benzyl)piperidin-4-yl]ethylcarbamate;
- 2-(methylamino)-2-oxoethyl 2-{l-[(3,4'-difluorobi-
phenyl-4-yl)methyl]piperidin-4-yl}ethylcarbamate;
- 2-(methylamino)-2-oxoethyl 2-{l-[(3-chloro-4'-fluoro-
biphenyl-4-yl)methyl]piperidin-4-yl}ethylcarbamate;
- 2-(methylamino)-2-oxoethyl 2-{l-[4-(4-chloro-3-
fluorophenoxy)benzyl]piperidin-4-yl}ethylcarbamate;
- 2-(methylamino)-2-oxoethyl {l-[3-(4-fluorophenoxy)-
benzyl]piperidin-4-yl}carbamate;
- 2-(methylamino)-2-oxoethyl {l-[3-(trifluoromethoxy)-
benzyl]piperidin-4-yljmethylcarbamate;
- 2-(methylamino)-2-oxoethyl {l-[4-(trifluoromethoxy)-
benzyl]piperidin-4-yl}methylcarbamate;

- 2-(methylamino)-2-oxoethyl {l-[3-(pyrimidin-2-yloxy)-
benzyl]piperidin-4-yl}methylcarbamate;
- 2-(methylamino)-2-oxoethyl 2-[1-(2-chloro-4-fluoro-
benzyl)piperidin-4-yl]ethylcarbamate;
- 2-(methylamino)-2-oxoethyl 2-[1-(3-chloro-4-fluoro-
benzyl)piperidin-4-yl]ethylcarbamate;
- 2-(methylamino)-2-oxoethyl 2-[1-(3-cyano-5-fluoro-
benzyl)piperidin-4-yl]ethylcarbamate;
- 2-(methylamino)-2-oxoethyl 2-{l-[3-(4-fluorophenoxy)-
benzyl]piperidin-4-yl}ethylcarbamate;
- 2-(methylamino)-2-oxoethyl (l-{ [3-(4-chlorophenyl)-
isoxazol-5-yl]methyl}piperidin-4-yl)methylcarbamate;
- 2-(methylamino)-2-oxoethyl (l-{[5-(4-chlorophenyl)-
1,3-oxazol-2-yl]methyl}piperidin-4-yl)methylcarbamate;
- 2-(methylamino)-2-oxoethyl [1-({4- [4-(trifluoro-
methyl)phenyl]-1,3-thiazol-2-yl}methyl)piperidin-4-yl]-
methylcarbamate;
- 2-(methylamino)-2-oxoethyl 2-(l-{[3-(4-chlorophenyl)-
isoxazol-5-yl]methyl}piperidin-4-yl)ethylcarbamate;
- 2-(methylamino)-2-oxoethyl 2-(1-{[5-(4-chlorophenyl)-
1,3-oxazol-2-yl]methyl}piperidin-4-yl)ethylcarbamate;
- 2-(methylamino)-2-oxoethyl 2-[1-({4-[4-(trifluoro-
methyl)phenyl]-1,3 -thiazol-2-yl}methyl)piperidin-4-yl]-
ethylcarbamate;
- 2-(methylamino)-2-oxoethyl (1-{2-[5-(4-chlorophenyl)-
isoxazol-3-yl]ethyl}piperidin-4-yl)methylcarbamate;
- 2-(methylamino)-2-oxoethyl 2-(l-{2-[3-(4-chloro-

phenyl)isoxazol-5-yl]ethyl}piperidin-4-yl)ethyl-
carbamate;
- 2-(methylamino)-2-oxoethyl (1-{2-[3-(4-chlorophenyl)-
isoxazol-5-yl]ethyl}piperidin-4-yl)methylcarbamate;
- 2-(methylamino)-2-oxoethyl (1-{3-[3-(4-chlorophenyl)-
isoxazol-5-yl]propyl}piperidin-4-yl)methylcarbamate;
- 2-(methylamino)-2-oxoethyl (1-{3-[5-(4-chlorophenyl)-
isoxazol-3-yl]propyl}piperidin-4-yl)methylcarbamate;
- 2-(methylamino)-2-oxoethyl {l-[1-(2-chloro-4-fluoro-
phenyl)ethyl]piperidin-4-yl}methylcarbamat e;
- 2-(methylamino)-2-oxoethyl (l-{l-[3-(4-chloro-
phenoxy)phenyl]ethyl}piperidin-4-yl)methylcarbamate;
- 2-(methylamino)-2-oxoethyl (1-{l-[2-chloro-3-(4-
chlorophenoxy)phenyl]ethyl}piperidin-4-yl)methyl-
carbamate ;
- 2-(methylamino)-2-oxoethyl 2-(1-{l-[3-(trifluoro-
methoxy)phenyl]ethyl}piperidin-4-yl)ethylcarbamate;
- 2-(methylamino)-2-oxoethyl 2-{l-[1-(2-chloro-4-
fluorophenyl)ethyl]piperidin-4-yl}ethylcarbamate;
- 2-(methylamino)-2-oxoethyl {l-[4-(4-chlorophenyl)but-
3-yn-1-yl]piperidin-4-yl}carbamate;
- 2-(methylamino)-2-oxoethyl {l-[5-(4-chlorophenyl)-
pent-4-yn-1-yl]piperidin-4-yl}carbamate;
- 2-(methylamino)-2-oxoethyl {l-[5-(2,5-dichloro-
phenyl)pent-4-yn-1-yl]piperidin-4-yl}carbamate;
- 2-(methylamino)-2-oxoethyl {l-[4-(4-chlorophenyl)but-
3-yn-1-yl]piperidin-4-yl}methylcarbamate;

- 2-(methylamino)-2-oxoethyl {l-[4-(4-chloro-2-fluoro-
phenyl)but-3-yn-1-yl]piperidin-4-yl}methylcarbamate;
- 2-(methylamino)-2-oxoethyl {l-[4-(2,5-dichloro-
phenyl)but-3-yn-l-yl]piperidin-4-yl}methylcarbamate.
Among the compounds of general formula (I) a
subclass of compounds is composed of the compounds of
the general formula (I'):

in which
m represents an integer from 1 to 4;
n represents an integer 1, 2 or 3;
o an integer 1 or 2;
A is selected from one or more groups X, Y and/or Z;
X represents a methylene group optionally
substituted by one or two Ci-6 alkyl, C3.7 cycloalkyl
or C3-7 cycloalkyl-C1-3 alkylene groups;
Y represents either a C2 alkenylene group optionally
substituted by one or two Ci-g alkyl, C3.7 cycloalkyl
or C3.7 cycloalkyl-C1-3 alkylene groups, or a C2
alkynylene group;
Z represents a group of formula:


p represents an integer from 1 to 5;
q and r represent integers and are defined such
that r+q is a number from 1 to 5;
B represents a covalent bond or a (Vs alkylene group;
G represents a covalent bond, an oxygen or sulphur
atom or a -CH(OH)-, CO, SO or S02 group;
Ri represents a group R4 optionally substituted by one
or more groups R5 and/or R6;
R4 represents a group selected from a furanyl,
pyrrolyl, thienyl, oxazolyl, isoxazolyl, thiazolyl,
isothiazolyl, imidazolyl, pyrazolyl, thiadiazolyl,
isothiadiazolyl, oxadiazolyl, thiadiazolyl,
triazolyl, tetrazolyl, phenyl, pyridinyl,
pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl,
naphthalenyl, quinolinyl, tetrahydroquinolinyl,
isoquinolinyl, tetrahydroisoquinolinyl,
phthalazinyl, quinazolinyl, quinoxalinyl,
cinnolinyl, naphthyridinyl, imidazopyrimidinyl,
thienopyrimidinyl, benzofuranyl, dihydrobenzo-
furanyl, benzothienyl, dihydrobenzothienyl,
benzimidazolyl, benzoxazolyl, benzisoxazolyl,
benzothiazolyl, benzisothiazolyl, indolyl,
isoindolyl, indazolyl, pyrrolopyridinyl,
furopyridinyl, dihydrofuropyridinyl,
thienopyridinyl, dihydrothienopyridinyl,
imidazopyridinyl, pyrazolopyridinyl,
oxazolopyridinyl, isoxazolopyridinyl,

thiazolopyridinyl;
R5 represents a halogen atom, a cyano, nitro,
hydroxyl, Ci-6 alkyl, Ci_6 alkoxy, Ci-6 thioalkyl, Cx.6
fluoroalkyl, Ci_6 f luoroalkoxy, Ci-6 fluorothioalkyl,
C3-7 cycloalkyl or C3-7 cycloalkyl-Ci-3 alkylene group
or a group NR7R8, NR7COR8, NR7C02R8, NR7S02R8, C0R7,
C02R7, CONR7R8, S02R7, S02NR7R8 or -0-(C1-3 alkylene)-
0-;
R6 represents a phenyl, phenyloxy, benzyloxy,
pyridinyl, pyrazinyl, pyridazinyl or pyrimidinyl
group; it being possible for the group or groups R6
to be substituted by one or more groups R5 identical
to or different from one another;
R7 and R8 represent independently of one another a
hydrogen atom or a Ci_6 alkyl group, or, with the
atom or atoms which carry them, form a ring
selected from an azetidine, pyrrolidine,
piperidine, morpholine, thiomorpholine, azepine or
piperazine ring, this ring being optionally
substituted by a Ci_6 alkyl or benzyl group;
R2 represents a hydrogen atom or a Ci-6 alkyl group;
R3 represents a hydrogen atom or a Ci-6 alkyl, C3.7
cycloalkyl or C3.7 cycloalkyl-Ci-3 alkylene group.
Among the compounds of general formula (I') a
first subgroup of compounds is composed of the
compounds for which:
m represents an integer from 1 to 3;

n represents an integer 1 or 2;
o an integer 2;
A is a methylene group;
B represents a covalent bond or a Ci-6 alkylene group,
more particularly a methylene or an ethylene;
G represents a covalent bond or an oxygen atom;
Ri represents a group R4 optionally substituted by one
or more groups R5 and/or R6/ more particularly by
one or two groups R5 and/or R6;
R4 represents a group selected from a phenyl,
pyridinyl, naphthalenyl, isoquinolinyl;
R5 represents a halogen atom, more particularly a
chlorine, a bromine or a fluorine, a cyano group,
an iV/itf-dimethylamino group, a Ci-6 alkyl group, more
particularly an isopropyl, a Ci-6 alkoxy group, more
particularly a methoxy or an ethoxy, or a Ci-6
fluoroalkyl group, more particularly a trifluoro-
methyl;
R6 represents a phenyl group;
R2 represents a hydrogen atom or a Ci-6 alkyl group;
R3 represents a hydrogen atom or a Ci-6 alkyl, C3-7
cycloalkyl or C3.7 cycloalkyl-Ci_3 alkylene group.
Among the compounds of general formula (I') a
second subgroup of compounds is composed of the
compounds for which:
m, n, o, A, B, G and Ri are as defined in subgroup 1;
R2 represents hydrogen atom;

R3 represents a hydrogen atom or a Ci-6 alkyl group, more
particularly a methyl.
Among the compounds of general formula (I')
mention may be made of the following compounds:
- 2-(methylamino)-2-oxoethyl {l-[(2-chlorophenyl)-
methyl]piperidin-4-yl}methylcarbamate;
- 2-(methylamino)-2-oxoethyl {l-[(4-chlorophenyl)-
methyl]piperidin-4-yl}methylcarbamate;
- 2-(methylamino)-2-oxoethyl {l-[(4-chlorophenyl)-
methyl]piperidin-4-yl}carbamate,•
- 2-(methylamino)-2-oxoethyl (1-[4-(1-methylethyl)-
phenyl]methyl piperidin-4-yl)methylcarbamate;
- 2-(methylamino)-2-oxoethyl [1-(biphenyl-4-ylmethyl)-
piperidin-4-yl]carbamate;
- 2-(methylamino)-2-oxoethyl [1-(biphenyl-4-ylmethyl)-
piperidin-4-yl]methylcarbamate;
- 2-(methylamino)-2-oxoethyl 2-[1-(biphenyl-4-yl-
methyl)piperidin-4-yl]ethylcarbamate;
- 2-(methylamino)-2-oxoethyl [1-(2-biphenyl-4-ylethyl)-
piperidin-4-yl]carbamate;
- 2-(methylamino)-2-oxoethyl [1-(naphthalen-2-yl-
methyl)piperidin-4-yl]methylcarbamate;
- 2-(methylamino)-2-oxoethyl 2-{l-[(4-bromophenyl)-
methyl]piperidin-4-yl}ethylcarbamate;
- 2-(methylamino)-2-oxoethyl 2-(1-{[3-(trifluoro-
methyl)phenyl]methyl}piperidin-4-yl)ethylcarbamate;
- 2 -(methyl amino)-2-oxoethyl 2-(l-{[4-(trifluoro-

methyl)phenyl]methyl}piperidin-4-yl)ethylcarbamate;
- 2-(methylamino)-2-oxoethyl 2-{l-[(2,3-dichloro-
phenyl)methyl]piperidin-4-yl}ethylcarbamate;
- 2-(methylamino)-2-oxoethyl 2-{l-[(3,4-dichloro-
phenyl)methyl]piperidin-4-yl}ethylcarbamate;
- 2-(methylamino)-2-oxoethyl 2-[1-(naphthalen-l-yl-
methyl )piperidin-4-yl]ethylcarbamate;
- 2-(methylamino)-2-oxoethyl 2-[1-(naphthalen-2-yl-
methyl)piperidin-4-yl]ethylcarbamate;
- 2-(methylamino)-2-oxoethyl 2-[1-(pyridin-2-yl-
methyl)piperidin-4-yl]ethylcarbamate;
- 2-(methylamino)-2-oxoethyl (l-{2-[4-fluoro-2-
(methyloxy)phenyl]ethyl}piperidin-4-yl)methylcarbamate;
- 2-(methylamino)-2-oxoethyl (l-{2-[(4-fluorophenyl)-
oxy]ethyl}piperidin-4-yl)carbamate;
- 2-(methylamino)-2-oxoethyl (1-{2-[(4-chlorophenyl)-
oxy]ethyl}piperidin-4-yl)carbamate;
- 2-(methylamino)-2-oxoethyl (l-{2-[(2,4-dichloro-
phenyDoxy] ethyl}piperidin-4-yl) carbamate;
- 2-(methylamino)-2-oxoethyl (1-{2-[(4-chlorophenyl)-
oxy]ethyl}piperidin-4-yl)methylcarbamate;
- 2-(methylamino)-2-oxoethyl l-{2-[(2,4-dichloro-
phenyl)oxy]ethyl} piperidin-4-yl)methylcarbamate;
- 2-(methylamino)-2-oxoethyl 2-(l-{2-[(4-fluorophenyl)-
oxy]ethyl}piperidin-4-yl)ethylcarbamate;
- 2-(methylamino)-2-oxoethyl 2-(1-{2-[(4-chlorophenyl)-
oxy]ethyl}piperidin-4-yl)ethylcarbamate;

- 2-(methylamino)-2-oxoethyl (l-{2-[ (4-fluorophenyl)-
oxy]ethyl} pyrrolidin-3-yl)methylcarbamate;
- 2-(methylamino)-2-oxoethyl (l-{2-[(4-chlorophenyl)-
oxy]ethyl}pyrrolidin-3-yl)methylcarbamate;
- 2-(methylamino)-2-oxoethyl (l-{2-[3-(trifluoro-
methyl)phenyl]ethyl}piperidin-4-yl)carbamate;
- 2-(methylamino)-2-oxoethyl {l-[2-(4-chlorophenyl)-
ethyl]piperidin-4-yl}carbamate;
- 2-(methylamino)-2-oxoethyl {l-[2-(4-cyanophenyl)-
ethyl]piperidin-4-yl}carbamate;
- 2-(methylamino)-2-oxoethyl (1-{2-[(isoquinolin-5-
yl)oxy]ethyl}piperidin-4-yl)carbamate;
- 2-(methylamino)-2-oxoethyl [1-(2-naphthalen-l-yl-
ethyl)piperidin-4-yl]carbamate;
- 2-(methylamino)-2-oxoethyl [1-(2-naphthalen-2-yl-
ethyl)piperidin-4-yl]carbamate;
- 2-(methylamino)-2-oxoethyl {l-[3-(4-chlorophenyl)-
propyl]piperidin-4-yl}carbamate;
- 2-(methylamino)-2-oxoethyl (1-{3-[4-(methyloxy)-
phenyl]propyl}piperidin-4-yl)carbamate;
- 2-(methylamino)-2-oxoethyl {l-[2-(3-chlorophenyl)-
ethyl]piperidin-4-yl}methylcarbamate;
- 2-(methylamino)-2-oxoethyl (1-{2-[4-(ethyloxy)-
phenyl]ethyl}piperidin-4-yl)methylcarbamate;
- 2-(methylamino)-2-oxoethyl (l-{2-[4-(dimethylamino)-
phenyl]ethyl}piperidin-4-yl)methylcarbamate;
- 2-(methylamino)-2-oxoethyl {l-[2-(2,4-dichloro-

phenyl)ethyl]piperidin-4-yl}methylcarbamate;
- 2-(methylamino)-2-oxoethyl [1-(2-naphthalen-l-yl-
ethyl)piperidin-4-yl]methylcarbamate;
- 2-(methylamino)-2-oxoethyl [1-U-naphthalen^-yl-
ethyDpiperidin^-y^methylcarbamate;
- 2-(methylamino)-2-oxoethyl (1-{3-[4-(methyloxy)-
phenyl]propyl}piperidin-4-yl)methylcarbamate;
- 2-(methylamino)-2-oxoethyl 2-{l-[2-(2-chlorophenyl)-
ethyl]piperidin-4-yl}ethylcarbamate;
- 2-(methylamino)-2-oxoethyl 2-{l-[2-(4-fluorophenyl)-
ethyl]piperidin-4-yl}ethylcarbamate;
- 2-(methylamino)-2-oxoethyl 2-(l-{2-[4-(ethyloxy)-
phenyl]ethyl}piperidin-4-yl)ethylcarbamate;
- 2-(methylamino)-2-oxoethyl 2-{l-[2-(2-chloro-6-
fluorophenyl)ethyl]piperidin-4-yl}ethylcarbamate;
- 2-(methylamino)-2-oxoethyl 2-(1-{3-[4-(methyloxy)-
phenyl]propyl}piperidin-4-yl)ethylcarbamate.
The compounds of general formula (I) may
include one or more asymmetric carbons. They may exist
in the form of enantiomers or diastereoisomers. These
enantiomers and diastereoisomers, and also mixtures
thereof, including the racemic mixtures, form part of
the invention.
The compounds of formula (I) may exist in the
form of bases or of addition salts with acids. Such
addition salts form part of the invention.
These salts are advantageously prepared with

pharmaceutically acceptable acids, although the salts
of other acids which are of use, for example, for
purifying or isolating compounds of formula (I)
likewise form part of the invention.
The compounds of general formula (I) may be
in the form of hydrates or solvates, namely in the form
of associations or combinations with one or more
molecules of water or with a solvent. Such hydrates and
solvates likewise form part of the invention.
In the context of the invention the terms are
understood as follows:
Ct-z/ where t and z may take the values from 1 to 7,
is a carbon chain which may have from t to z carbon
atoms; for example, Ci-3 is a carbon chain which may
have from 1 to 3 carbon atoms;
alkyl is a saturated, linear or branched aliphatic
group; for example, a Ci-6 alkyl group represents a
linear or branched carbon chain of 1 to 6 carbon
atoms, more particularly a methyl, ethyl, propyl,
isopropyl, butyl, isobutyl, tert-butyl, pentyl or
hexyl;
alkylene is a saturated, linear or branched
divalent alkyl group; for example, a Ci-3 alkylene
group represents a linear or branched, divalent
carbon chain of 1 to 3 carbon atoms, more
particularly a methylene, ethylene, 1-methyl-
ethylene or propylene;

cycloalkyl is a cyclic alkyl group; for example, a
C3-7 cycloalkyl group represents a cyclic carbon
group of 3 to 7 carbon atoms, more particularly a
cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or
cycloheptyl;
alkenylene is a divalent unsaturated aliphatic
group having 2 carbons, more particularly an
ethylene;
C2 alkynylene is a -CsC- group;
alkoxy is an -O-alkyl group having a saturated,
linear or branched aliphatic chain;
thioalkyl is an -S-alkyl group having a saturated,
linear or branched aliphatic chain;
fluoroalkyl is an alkyl group of which one or more
hydrogen atoms have been substituted by a fluorine
atom;
fluoroalkoxy is an alkoxy group of which one or
more hydrogen atoms have been substituted by a
fluorine atom;
fluorothioalkyl is a thioalkyl group of which one
or more hydrogen atoms have been substituted by a
fluorine atom; and
halogen atom is a fluorine, a chlorine, a bromine
or an iodine.
In the text below, a protective group Pg is
understood to be a group which makes it possible on the
one hand for a reactive function such as a hydroxyl or

an amine to be protected during a synthesis and on the
other hand for the reactive function to be regenerated
intact at the end of synthesis. Examples of protective
groups and also of methods of protection and
deprotection are given in "Protective Groups in Organic
Synthesis", Green et al., 2nd Edition (John Wiley &
Sons, Inc., New York).
The compounds of the invention may be
prepared according to various methods, which are
illustrated by scheme 1 below.
Thus a first method (scheme 1) involves
reacting a compound of general formula (II), in which
B, R2, n and o are as defined in the general formula
(I), with a derivative of general formula (III), in
which W represents a mesylate or tosylate group or a
chlorine, bromine or iodine atom and m, G, A and Ri are
as defined in the general formula (I), in the presence
of a base such as triethylamine, sodium hydride, sodium
tert-butoxide or sodium carbonate in a solvent such as
tetrahydrofuran, acetonitrile, dimethyl sulphoxide or
dimethylformamide at a temperature between 0°C and the
reflux temperature of the solvent.


The oxazolidine-dione of general formula
(Ila) thus obtained is subsequently converted into a
compound of general formula (I), by aminolysis using an
amine of general formula R3NH2 in which R3 is as defined
in the general formula (I). The aminolysis reaction may
be carried out in a solvent such as methanol, ethanol
or a solvent mixture such as methanol and
tetrahydrofuran or methanol and dioxane.
A variant form of obtaining compounds of
general formula (I) (scheme 1) involves converting a
compound of general formula (II) as defined above by

aminolysis, under the conditions described above, using
an amine of general formula R3NH2 as defined above, to
give a carbamate-amide derivative of general formula
(la) in which B, R2, R3, n and o are as defined in the
general formula (I). The compound of general formula
(I) is then obtained by reacting the compound (la) with
a derivative of general formula (III) as defined above,
under the conditions described above.
The carbamate-amide derivative of general
formula (la) as defined above may also be obtained from
the carbamate-ester of general formula (lb), in which
B, R2, n and o are as defined in the general formula
(I), PG represents a protective group such as a Boc
(tert-butyloxycarbonyl) and R represents a methyl or
ethyl group, by aminolysis using an amine of general
formula R3NH2 as defined above and under the conditions
described above, then by deprotection, in the presence
for example of a solution of hydrochloric acid (5N) in
isopropanol.
The carbamate-esters (lb) may be prepared
according to the method illustrated by scheme 2 below.


According to scheme 2 the carbamate-ester of
general formula (lb) is obtained by reacting an amine
of general formula (IV), in which B, n and o are as
defined in the general formula (I) and PG represents a
protective group such as a Boc, with a carbonate of
general formula (V), in which V represents a hydrogen
atom or a nitro group, R2 is as defined in the general
formula (I) and R represents a methyl or ethyl group.
When the method of preparing them is not
described the compounds of general formula (II) may be
prepared according to methods which are described in
the literature or according to methods similar to those
described or known to the skilled person.
The carbonates of general formula (V) may be
prepared according to any method described in the
literature, by reaction for example of an alcohol of
general formula HOCHR2COOR where R represents a methyl
or ethyl group with phenyl chloroformate or 4-nitro-
phenyl chloroformate in the presence of a base such as
triethylamine or diisopropylethylamine.
The compounds of general formulae (III) and
(IV) and the amines of general formula R3NH2 are
available commercially or are prepared according to
methods which are described in the literature or which
are known to the skilled person.
The compounds of general formula (la) in
which B, R2, R3, n and o are as defined in the general

formula (I) are novel and likewise form part of the
invention. They are useful as synthesis intermediates
for the preparation of compounds of general formula
(I).
The compounds of general formula (Ila) in
which m, G, A, Ri, B, R2, n and o are as defined in the
general formula (I), with the exception of the compound
3-[1-(phenylmethyl)-4-piperidinyl]-2,4-oxazolidine-
dione, are novel and likewise form part of the
invention. They are useful as synthesis intermediates
for preparing compounds of general formula (I).
The examples which now follow illustrate the
preparation of some compounds of the invention. These
examples are not limitative and serve merely to
illustrate the invention. The microanalyses, the IR and
NMR spectra and/or the LC-MS (liquid chromatography
coupled to mass spectroscopy) confirm the structures
and the purities of the compounds obtained.
M.P. (°C) represents the melting point in
degrees Celsius.
The numbers indicated between brackets in the
titles of the examples correspond to those in the 1st
column of the subsequent table.
Example 1 (compound 25)
2-(methylamino)-2-oxoethyl 2-[1-(biphenyl-4-ylmethyl)-
piperidin-4-yl]ethylcarbamate


1.1. 3-(2-piperidin-4-ylethyl)-1,3-oxa-
zolidine-2;4-dione hydrochloride
A solution of 10 g (77.40 mmol) of
2-piperidin-4-ylethanol, 22.33 g (85.14 mmol) of
triphenylphosphine and 9.3 9 g (92.88 mmol) of 1,3-oxa-
zolidine-2,4-dione (J. Med. Chem. 1991, 34, 1538-44) in
150 ml of tetrahydrofuran, cooled to approximately
-10°C, is admixed dropwise under an inert atmosphere
with a solution of 15.65 g (77.40 mmol) of diisopropyl
azodicarboxylate (DIAD) in 25 ml of tetrahydrofuran,
during which the temperature of the reaction mixture is
held between -10°C and 0°C. Stirring is continued at
0°C for 1 hour and then at 25°C for 22 hours. The solid
formed is collected by filtration, washed repeatedly
with tetrahydrofuran and then dried under vacuum at
approximately 70°C. This solid is then taken up in a
solution of hydrochloric acid (5N) in isopropanol. The
solid formed is collected by filtration and then washed
with ethyl acetate and ether.
Drying under vacuum at approximately 70°C
gives 6.45 g of hydrochloride in the form of a white
solid.
M.P. (°C): 178°C
1.2. 3-{2-[l-(biphenyl-4-ylmethyl)piperidin-
4-yl]ethyl}-l,3-oxazolidine-2,4-dione

A solution of 0.40 g (1.61 mmol) of
3-(2-piperidin-4-ylethyl)-1,3-oxazolidine-2,4-dione
hydrochloride, prepared in step 1.1., 0.326 g
(1.61 mmol) of 4-(chloromethyl)biphenyl and 0.51 g
(4.82 mmol) of sodium carbonate in 3 ml of acetonitrile
is heated at reflux for 17 hours. It is left to return
to ambient temperature and filtered and the filtrate is
concentrated under reduced pressure. The residue is
taken up in dichloromethane and water and the aqueous
phase is separated off and extracted twice with
dichloromethane. The combined organic phases are washed
with saturated aqueous sodium chloride solution and
dried over sodium sulphate. Following evaporation of
the solvent, the residue obtained is purified by
chromatography on silica gel, eluting with a 97/3 then
95/5 mixture of dichloromethane and methanol.
This gives 0.46 g of product in the form of a
beige solid.
1.3. 2-(methylamino)-2-oxoethyl 2-[l-(bi-
phenyl-4-ylmethyl)piperidin-4-yl]ethylcarbamate
A solution of 0.45 g (1.19 mmol) of
3-{2-[1-(biphenyl-4-ylmethyl)piperidin-4-yl]ethyl}-l,3-
oxazolidine-2,4-dione, obtained in step 1.2., in 5 ml
of methanol is admixed with 3 ml (5.97 mmol) of a
solution of methylamine (2M) in tetrahydrofuran.
Stirring is continued at ambient temperature for 17
hours. Following concentration under reduced pressure,

the residue obtained is purified by chromatography on
silica gel, eluting with a 95/5 then 90/10 mixture of
dichloromethane and methanol. A yellow paste is
obtained which is crystallized from diisopropyl ether.
This gives 0.40 g of product in the form of a
yellow solid.
LC-MS: M+H = 410
M.P. (°C): 106-110°C
XH NMR (CDC13) 5 (ppm) : 1.2-1.50 (unresolved complex,
5H); 1.70 (m, 2H); 2.0 (broad t, 2H); 2.90 (d, 3H); 3.0
(m, 2H); 3.30 (q, 2H); 3.55 (s, 2H); 4.60 (s, 2H); 4.80
(broad s, 1H) ; 6.15 (broad s, 1H) ; 7.40 (m, 5H) ; 7.60
(m, 4H).
Example 2 (compound 52)
2-(methylamino)-2-oxoethyl l-{2-[4-fluoro-2-(methoxy)-
phenyl]ethyl}piperidin-4-yl)methylcarbamate

2.1. 1,1-dimethylethyl 4-
{[(methylsulphonyl)oxy]methyl}piperidine-l-carboxylate
A solution of 10.08 g (46.81 mmol) of
1,1-dimethylethyl 4-(hydroxymethyl)piperidine-l-
carboxylate and 9.90 ml (70.21 mmol) of triethylamine
in 100 ml of dichloromethane, cooled to approximately

0°C, is admixed dropwise under an inert atmosphere with
a solution of 4 ml (51.49 mmol) of mesyl chloride in
10 ml of dichloromethane. The bath is removed and
stirring is continued at ambient temperature for 30
minutes. Water is added to the reaction mixture, the
aqueous phase is separated off and extracted once with
dichloromethane, the combined organic phases are wasHed
with water and dried over sodium sulphate and the
filtrate is concentrated under reduced pressure.
This gives 13.7 g of product in the form of
an orange-coloured oil, which is used as it is in the
following step.
2.2. 1,1-dimethylethyl 4-[ (2,4-dioxo-l,3-
oxazolidin-3-yl)methyl]piperidine-1-carboxylate
A suspension of 13.60 g (46.36 mmol) of
1,1-dimethylethyl 4-{[(methylsulphonyl)oxy]methyl}-
piperidine-1-carboxylate, prepared in step 2.1., 9.37 g
(92.72 mmol) of 1,3-oxazolidine-2,4-dione and 16.02 g
(139.08 mmol) of 1,1,3,3-tetramethylguanidine in a
mixture of 180 ml of tetrahydrofuran and 3 0 ml of
dimethylformamide is heated at reflux for 24 hours. It
is allowed to return to ambient temperature and is
concentrated under reduced pressure. The residue is
taken up in dichloromethane and water and the aqueous
phase is separated off and extracted twice with
dichloromethane. The combined organic phases are washed
with saturated aqueous sodium chloride solution and

dried over sodium sulphate. Following evaporation of
the solvent, the residue obtained is purified by-
chroma tography on silica gel, eluting with a 98/2 then
95/5 mixture of dichloromethane and methanol.
This gives 12.53 g of product in the form of
an orange-brown solid.
2.3. 3-(piperidin-4-ylmethyl) -1, 3 -
oxazolidine-2,4-dione hydrochloride
A suspension of 12.51 g (41.95 mmol) of
1,1-dimethylethyl 4-[(2,4-dioxo-l,3-oxazolidin-3-yl)-
methyl]piperidine-l-carboxylate, obtained in step 2.2.,
in 65 ml of dioxane is admixed with 38.10 ml
(209.75 mmol) of a solution of hydrochloric acid (5N)
in isopropanol. Stirring is continued at approximately
60°C for 17 hours. The suspension is allowed to return
to ambient temperature. The solid formed is collected
by filtration and then washed repeatedly with ether and
dried under vacuum at approximately 70°C.
This gives 8.41 g of product in the form of a
white solid.
M.P. (°C): 195-200°C
2.4. 3- [ (l-{2- [4-fluoro-2-(methoxy)phenyl]-
ethyl}piperidin-4-yl)methyl]-1,3-oxazolidine-2,4-dione
The method described in Example 1 (step 1.2.)
is used. Starting from 0.4 0 g (1.70 mmol) of
3-(piperidin-4-ylmethyl)-1,3-oxazolidine-2,4-dione
hydrochloride, prepared in step 2.3., 0.423 g

(1.70 mmol) of 2-[4-fluoro-2-(methyloxy)phenyl]ethyl
methanesulphonate [EP1340761] and 0.54 g (5.11 mmol) of
sodium carbonate gives, after treatment, 0.590 g of
product in the form of a viscous yellow oil, which is
used as it is in the following step.
2.5. 2-(methylamino)-2-oxoethyl l-{2-[4-
fluoro-2 -(methoxy)phenyl]ethyl]piperidin-4-yl)methyl-
carbamate
The procedure described in Example 1 (step
1.3.) is followed. Starting from 0.58 g (1.66 mmol) of
3-[(l-{2-[4-fluoro-2-(methoxy)phenyl]ethyl}piperidin-4-
yl)methyl]-1,3-oxazolidine-2,4-dione, prepared in step
2.4., and 8.28 ml (16.55 mmol) of a solution of methyl-
amine (2M) in tetrahydrofuran, and after chromatography
on silica gel, eluting with a 95/5/0.5 mixture of
dichloromethane, methanol and 28% ammonia, followed by
washing with diisopropyl ether, gives 0.315 g of
product in the form of a white solid.
LC-MS: M+H =3 82
M.P. (°C): 126-128°C
XH NMR (DMSO) 6 (ppm) : 1.10 (m, 2H); 1.35 (broad s, 1H) ;
1.60 (broad d, 2H); 1.85 (broad t, 2H); 2.40 (m, 2H);
2.60 (m, 5H); 2.90 (m, 4H); 3.80 (s, 3H); 4.30 (s, 2H) ;
6.65 (td, 1H); 6.80 (dd, 1H); 7.15 (m, 2H); 7.70 (broad
s, 1H). I

Example 3 (compound 68)
2-(methylamino)-2-oxoethyl l-{2-[(2,4-dichlorophenyl)-
oxy]ethyl}piperidin-4-yl)carbamate

3.1. 1,1-dimethylethyl 4-[({[2-(ethyloxy)-2-
oxoethyl]oxyjcarbonyl)amino]piperidine-1-carboxylate
A suspension of 5.09 g (25.42 mmol) of
1,1-dimethylethyl 4-aminopiperidine-l-carboxylate and
13.45 g (59.99 mmol) of ethyl [(phenyloxycarbonyl)oxy]-
acetate (J. Med. Chem., 1999, 42, 277-90) in 300 ml of
toluene is heated at reflux for 30 hours.
The suspension is allowed to return to
ambient temperature, the insoluble material is
separated off by filtration and the filtrate is
concentrated under reduced pressure. The residue thus
obtained is purified by chromatography on silica gel,
eluting with a 3 0/70 mixture of ethyl acetate and
cyclohexane.
This gives 6.62 g of product in the form of a
light-coloured yellow oil.
3.2. 1,1-dimethylethyl 4-[({[2-(methyl-
amino)-2-oxoethyl]oxy}carbonyl)amino]piperidine-1-
carboxylate
The procedure of Example 1 (step 1.3.) is

repeated. Starting from 6.33 g (19.16 mmol) of 1,1-di-
methylethyl 4-[({[2-(ethyloxy)-2-oxoethyl]oxy}-
carbonyl)amino]piperidine-1-carboxylate, prepared in
step 3.1., and 47.90 ml (95.81 mmol) of a solution of
methylamine (2M) in tetrahydrofuran gives 5.90 g of
product in the form of a sticky yellow paste.
3.3. 2-(methylamino)-2-oxoethyl piperidin-4-
ylcarbamate hydrochloride
The method described in Example 2 (step 2.3.)
is used. Starting from 5.90 g (18.71 mmol) of
1,1-dimethylethyl 4-[({[2-methylamino)-2-oxoethyl]oxy}-
carbonyl)amino]piperidine-1-carboxylate, prepared in
step 3.2., and 17 ml (93.53 mmol) of a solution of
hydrochloric acid (5N) in isopropanol gives 3.83 g of
hydrochloride in the form of a white solid after
washing with diisopropyl ether and drying under vacuum
at approximately 70°C.
M.P. (°C): 153°C
3.4. 2-(methylamino)-2-oxoethyl l-{2-[2,4-
dichlorophenyl)oxy]ethyl}piperidin-4-yl)carbamate
The method described in Example 1 (step 1.2.)
is used. Starting from 0.51 g (1.89 mmol) of 2-(methyl-
amino) -2-oxoethyl piperidin-4-ylcarbamate hydro-
chloride, prepared in step 3.3., 0.50 g (1.99 mmol) of
1-[(2-bromoethyl)oxy]-2,4-dichlorobenzene and 0.60 g
(5.68 mmol) of sodium carbonate, and after
chromatography on silica gel, eluting with a 94/6/0.6

then 95/5/0.5 mixture of dichloromethane, methanol and
28% ammonia, followed by washing with diisopropyl
ether, gives 0.44 g of product in the form of a white
solid.
LC-MS: M+H =404
M.P. (°C): 115-119°C
AH NMR (CDC13) 5 (ppm) : 1.50 (m, 2H) ; 2.0 (broad d, 2H) ;
2.35 (broad t, 2H); 2.90 (d, 3H); 3.0 (m, 4H); 3.60 (m,
1H); 4.15 (t, 2H); 4.60 (s, 2H); 4.75 (broad d, 1H);
6.15 (broads, 1H); 6.85 (d, 1H); 7.20 (dd, 1H); 7.40
(d, 1H) .
Example 4 (compound 4)
2-(methylamino)-2-oxoethyl {l-[(4-chlorophenyl)methyl] -
piperidin-4-yl}methylcarbamate hydrochloride

4.1. 2-(methylamino)-2-oxoethyl (piperidin-
4-yl)methylcarbamate hydrochloride
A solution of 0.50 g (2.13 mmol) of
3-piperidin-4-ylmethyl)-1,3-oxozolidine-2,4-dione
hydrochloride, obtained in step 2.3., and 5.3 0 ml
(10.65 mmol) of a solution of methylamine (2M) in
tetrahydrofuran in 10 ml of methanol is stirred at
ambient temperature for 15 hours. Following
concentration under reduced pressure, the residue
obtained is treated with a solution of hydrochloric

acid (5N) in isopropanol. The hydrochloride obtained is
collected by filtration, washed with diisopropyl ether
and dried under vacuum at approximately 70°C. This
gives 0.49 g of a white powder.
4.2. 2-(methylamino)-2-oxoethyl {l-[(4-
chlorophenyl)methyl]piperidin-4-yl}methylcarbamate
hydrochloride
A mixture of 0.118 g (0.44 mmol) of
2-(methylamino)-2-oxoethyl (piperidin-4-
yl)methylcarbamate hydrochloride, 0.283 g (1.33 mmol)
of sodium triacetoxyborohydride and 0.626 g (4.45 mmol)
of 4-chlorobenzaldehyde in 5 ml of a 1% solution of
acetic acid in N,N'-dimethylformamide is stirred at
ambient temperature. After 24 hours of stirring, 2 g of
DOWEX 50WX2 acidic resin (Fluka) are added and stirring
is continued at ambient temperature for one hour. The
mixture is filtered and the resin is rinsed with 3
times 5 ml of N,N'-dimethylformamide, 3 times 5 ml of
dichloromethane and 3 times 5 ml of methanol. The resin
is subsequently treated for an hour at ambient
temperature with 8 ml of a solution (2M) of ammonia in
methanol. The mixture is filtered and the filtrate is
concentrated under vacuum. The product is purified by
chromatography on silica gel, eluting with a 94/6
mixture of dichloromethane and methanol containing 2%
of 28% aqueous ammonia solution. The oily residue
obtained is treated with 5 ml of a solution of

hydrochloric acid (0.1N) in isopropanol. Concentration
gives 0.067 g of a white powder.
M.P. (8C): 220-222°C
LC-MS: M+H = 354
XH NMR (DMSO-dg / D20): 8 (ppm): 1.20 (m, 2H); 1.40 (m,
1H); 1.60 (m, 2H); 1.90 (t, 2H); 2.70 (s, 3H); 2.75 (d,
2H); 2.90 (d, 2H); 3.40 (s, 2H); 4.30 (s, 2H); 7.95 (m,
4H) .
Table 1 below illustrates the chemical
structures and the physical properties of some
compounds according to the invention.
In this table:
- in the "base or salt" column, "base" signifies that
the compound is in the form of the free base, whereas
"HCl" represents a compound in hydrochloride form, and
the ratio between brackets is the (acid:base) ratio,
- t-BuO, Me, Et and i-Pr represent, respectively, tert-
butoxy, methyl, ethyl and isopropyl groups, and
- Ph represents a phenyl group.
























The compounds of the invention were subjected
to pharmacological tests allowing determination of
their inhibitory effect on the enzyme FAAH (fatty acid
amide hydrolase).
The inhibitory activity was demonstrated in a
radioenzymatic assay based on measuring the product of
hydrolysis ( [1-3H] ethanolamine) of anandamide [1-3H
ethanol amine] by FAAH (Life Sciences (1995), 56, 1999-
2005 and Journal of Pharmacology and Experimental
Therapeutics (1997), 283, 729-734). Accordingly, mouse
brains (minus the cerebellum) are removed and stored at
-80°C. Membrane homogenates are prepared at the time of
use by homogenizing the tissues in a Polytron in a
10 mM Tris-HCl buffer (pH 8.0) containing 150 mM NaCl
and 1 mM EDTA. The enzymatic reaction is subsequently
conducted in 70 /xl of buffer containing bovine serum

albumin without fatty acids (l mg/ml). In succession
the test compounds, at various concentrations,
anandamide [1-3H ethanolamine] (specific activity:
15-20 Ci/mmol) diluted to 10 /xM with cold anandamide,
and the membrane preparation (400 //g of frozen tissue
per assay) are added. After 15 minutes at 25°C, the
enzymatic reaction is terminated by adding 140 /xl of
chloroform/methanol (2:1). The mixture is stirred for
10 minutes and then centrifuged for 15 minutes at
3500 g. An aliquot (30 (il) of the aqueous phase
containing the ethanolamine [1-3H] is counted by liquid
scintillation.
Under these conditions the most active
compounds of the invention exhibit IC50 values
(concentration inhibiting by 50% the control enzymatic
activity of FAAH) of between 0.001 and 1 /iM.
Table 2 below presents the IC50 values of some
compounds according to the invention.

It is therefore apparent that the compounds
according to the invention have an inhibitory activity
on the FAAH enzyme.
The in vivo activity of the compounds of the

Accordingly, intraperitoneal (i.p.)
administration of PBQ (phenylbenzoquinone, 2 mg/kg in a
0.9% sodium chloride solution containing 5% of ethanol)
to male OF1 mice weighing 2 5 to 30 g causes abdominal
stretches, on average 30 twists or contractions during
the period from 5 to 15 minutes after injection. The
test compounds are administered orally (p.o.) or
intraperitoneally (i.p.) in suspension in Tween 80 at
0.5%, 60 minutes or 120 minutes before the
administration of PBQ. Under these conditions the most
potent compounds of the invention reduce by 35% to 70%
the number of stretches induced by PBQ, within a dose
range of between 1 and 3 0 mg/kg.
For example, compound 26 of the table reduces
by 56% the number of stretches induced by PBQ, at a
dose of 10 mg/kg p.o. at 12 0 minutes.
The enzyme FAAH (Chemistry and Physics of
Lipids, (2000), 108, 107-121) catalyses the hydrolysis
of endogenous derivatives of amides and of esters of
various fatty acids such as N-arachidonoylethanolamine
(anandamide), W-palmitoylethanolamine, .N-oleoyl-
ethanolamine, oleamide or 2-arachidonoylglycerol. These
derivatives exert various pharmacological activities by
interacting, inter alia, with cannabinoid and vanilloid
receptors.
The compounds of the invention block this
degradation pathway and increase the tissue level of

these endogenous substances. They can be used in this
respect in the prevention and treatment of pathologies
in which endogenous cannabinoids and/or any other
substrates metabolized by the FAAH enzyme are involved.
Mention may be made, for example, of the
following diseases and conditions:
pain, especially acute or chronic pain of neurogenic
type: migraine, neuropathic pain, including forms
associated with the herpes virus and with diabetes;
acute or chronic pain associated with inflammatory
diseases: arthritis, rheumatoid arthritis, osteo-
arthritis, spondylitis, gout, vasculitis, Crohn's
disease, irritable bowel syndrome;
acute or chronic peripheral pain;
dizziness, vomiting, nausea, especially those
subsequent to chemotherapy;
eating disorders, especially anorexia and cachexia of
various kinds;
neurological and psychiatric pathologies: shaking,
dyskinesia, dystonia, spasticity, obsessive-compulsive
behaviours, Tourette's syndrome, all forms of
depression and anxiety of any kind and cause, mood
disorders, psychoses;
acute and chronic neurodegenerative diseases:
Parkinson's disease, Alzheimer's disease, senile
dementia, Huntington's chorea, lesions associated with
cerebral ischemia and with cranial and medullary

trauma;
epilepsy;
sleep disorders, including sleep apnoea;
cardiovascular diseases, especially hypertension,
cardiac arrhythmias, arteriosclerosis, heart attack,
cardiac ischemias;
renal ischemia;
cancej?«T benign skin tumours, papillomas and brain
tumours, prostate tumours, brain tumours (glio-
blastomas, medulloepitheliomas, medulloblastomas,
neuroblastomas, tumours of embryonic origin, astro-
cytomas, astroblastomas, ependyomas, oligodendro-
gliomas, plexus tumour, neuroepitheliomas, epiphysial
tumour, ependymoblastomas, malignant meningiomas,
sarcomatoses, malignant melanomas, schwannomas);
disorders of the immune system7™especially autoimmune
diseases: psoriasis, lupus erythematosis, diseases of
the connective tissue or collagen diseases, Sjogren's
syndrome, ankylosing spondylarthritis, undifferentiated
spondylarthritis, Behcet's disease, haemolytic auto-
immune anaemias, multiple sclerosis, amyotrophic
lateral sclerosis, amyloses, transplant rejection,
diseases affecting the plasmocytic line;
allergic diseases: immediate or delayed hyper-
sensitivity, allergic rhinitis or conjunctivitis,
contact dermatitis;
parasitic, viral or bacterial infectious diseases:

AIDS, meningitis; inflammatory diseases, especially
diseases of the joints: arthritis, rheumatoid
arthritis, osteoarthritis, spondylitis, gout,
vasculitis, Crohn's disease, irritable bowel syndrome;
osteoporosis; ocular conditions: ocular hypertension,
glaucoma;
pulmonary conditions: diseases of the respiratory
tract, bronchospasms, coughing, asthma, chronic
bronchitis, chronic obstruction of the respiratory
tract, emphysema;
gastrointestinal diseases: irritable bowel syndrome,
intestinal inflammatory disorders, ulcers, diarrhoea;
urinary incontinence and bladder inflammation.
The use of a compound of formula (I) in base,
salt, hydrate or pharmaceutically acceptable solvate
form for preparing a medicinal product intended for
treating the abovementioned pathologies forms an
integral part of the invention.
The invention likewise provides medicinal
products which comprise a compound of formula (I), or a
salt or else a hydrate or a pharmaceutically acceptable
solvate of the compound of formula (I). These medicinal
products are employed in therapy, particularly in the
treatment of the abovementioned pathologies.
According to another of its aspects the
present invention provides pharmaceutical compositions
comprising as active principle at least one compound

according to the invention. These pharmaceutical
compositions include an effective dose of a compound
according to the invention, or a salt or a hydrate or a
pharmaceutically acceptable solvate of the said
compound, and, optionally, one or more pharmaceutically
acceptable excipients.
The said excipients are selected, according
to the pharmaceutical form and the desired mode of
administration, from the customary excipients, which
are known to the skilled person.
In the pharmaceutical compositions of the
present invention for oral, sublingual, subcutaneous,
intramuscular, intravenous, topical, local, intra-
thecal, intranasal, transdermal, pulmonary, ocular or
rectal administration, the active principle of formula
(I) above, or its salt, solvate or hydrate where
appropriate, may be administered in a single-dose
administration form, in a mixture with conventional
pharmaceutical excipients, to animals and to humans for
the prophylaxis or treatment of the above disorders or
diseases.
The unit-dose administration forms which are
appropriate include oral forms such as tablets, soft or
hard gelatine capsules, powders, granules, chewing gums
and oral solutions or suspensions, forms for
sublingual, buccal, intratracheal, intraocular and
intranasal administration, and for administration by

inhalation, forms for subcutaneous, intramuscular or
intravenous administration and forms for rectal or
vaginal administration. For topical application the
compounds according to the invention may be used in
creams, ointments or lotions.
By way of example a single-dose
administration form of a compound according to the
invention in tablet form may comprise the following
components:
Compound according to the invention 50.0 mg
Mannitol 223.75 mg
Croscaramellose sodium 6.0 mg
Maize starch 15.0 mg
Hydroxypropyl-methylcellulose 2.25 mg
Magnesium stearate 3.0 mg
The said single-dose forms contain a dose
permitting daily administration of 0.01 to 2 0 mg of
active principle per kg of body weight, depending on
the pharmaceutical form.
There may be particular cases in which higher
or lower dosages are appropriate; such dosages also
belong to the invention. In accordance with customary
practice, the dosage appropriate to each patient is
determined by the doctor according to the mode of
administration, the weight and the response of the said
patient.
According to another of its aspects the

invention also provides a method of treating the
pathologies indicated above, which comprises
administering an effective dose of a compound according
to the invention, one of its pharmaceutically
acceptable salts, a solvate or a hydrate of the said
compound.

We claim:
1. Compound of the formula (I)

in which
m represents an integer from 1 to 4;
n represents an integer 1, 2 or 3;
o an integer 1 or 2;
A is selected from one or more groups X, Y and/or Z;
X represents a methylene group optionally
substituted by one or two C1-6 alkyl, C3-7 cycloalkyl
or C3-7 cycloalkyl-C1-3 alkylene groups;
Y represents either a C2 alkenylene group optionally
substituted by one or two C1-6 alkyl, C3-7 cycloalkyl
or C3-7 cycloalkyl-C1-3 alkylene groups, or a C2
alkynylene group;
Z represents a group of formula:

p represents an integer from 1 to 5;
q and r represent integers and are defined such
that r+q is a number from 1 to 5;
B represents a covalent bond or a C1-6 alkylene group;

G represents a covalent bond, an oxygen or sulphur atom
or a -CH(OH)-, CO, SO or SO2 group;
R1 represents a group R4 optionally substituted by one
or more groups R5 and/or R6;
R4 represents a group selected from a furanyl,
pyrrolyl, thienyl, oxazolyl, isoxazolyl, thiazolyl,
isothiazolyl, imidazolyl, pyrazolyl, thiadiazolyl,
isothiadiazolyl, oxadiazolyl, thiadiazolyl,
triazolyl, tetrazolyl, phenyl, pyridinyl,
pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl,
naphthalenyl, quinolinyl, tetrahydroquinolinyl,
isoquinolinyl, tetrahydroisoquinolinyl, phthalazinyl,
quinazolinyl, quinoxalinyl, cinnolinyl,
naphthyridinyl, imidazopyrimidinyl,
thienopyrimidinyl, benzofuranyl, dihydrobenzofuranyl,
benzothienyl, dihydrobenzothienyl, benzimidazolyl,
benzoxazolyl, benzisoxazolyl, benzothiazolyl,
benzisothiazolyl, indolyl, isoindolyl, indazolyl,
pyrrolopyridinyl, furopyridinyl,
dihydrofuropyridinyl, thienopyridinyl,
dihydrothienopyridinyl, imidazopyridinyl,
pyrazolopyridinyl, oxazolopyridinyl,
isoxazolopyridinyl, thiazolopyridinyl;
R5 represents a halogen atom, a cyano, nitro,
hydroxyl, C1-6 alkyl, C1-6 alkoxy, C1-6 thioalkyl, C1-6
fluoroalkyl, C1-6 fluoroalkoxy, C1-6 fluorothioalkyl, C3-
7 cycloalkyl or C3-7 cycloalkyl-C1-3 alkylene group or a
group NR7R8, NR7CORB, NR7CO2R8, NR7SO2R8, COR7,

CO2R7, CONR7R8, SO2R7, SO2NR7R8 or -O-(C1-3 alkylene)-O-;
R6 represents a phenyl, phenyloxy, benzyloxy,
pyridinyl, pyrazinyl, pyridazinyl, pyrimidinyl or
pyrimidinyloxy group; it being possible for the group
or groups R6 to be substituted by one or more groups
R5 identical to or different from one another;
R7 and R8 represent independently of one another a
hydrogen atom or a C1-6 alkyl group, or, with the atom
or atoms which carry them, form a ring selected from
an azetidine, pyrrolidine, piperidine, morpholine,
thiomorpholine, azepine or piperazine ring, this ring
being optionally substituted by a C1-6 alkyl or benzyl
group;
R2 represents a hydrogen atom or a C1_6 alkyl group;
R3 represents a hydrogen atom or a C1-6 alkyl, C3-7
cycloalkyl or C3-7 cycloalkyl-C1-3 alkylene group;
in the form of a base, addition salt with an acid,
hydrate or solvate.
2. Compound of formula (I) as claimed in claim 1,
wherein
m represents an integer from 1 to 4;
n represents an integer 1 or 2;
o an integer 1 or 2;
A is selected from one or more groups X and/or Y;
X represents a methylene group optionally substituted
by one or two C1-6 alkyl groups;
Y represents a C2 alkynylene group;

B represents a covalent bond or a C1-6 alkylene group;
G represents a covalent bond or an oxygen atom;
R1 represents a group R4 optionally substituted by one
or more groups R5 and/or R6;
R4 represents a group selected from an oxazolyl,
isoxazolyl, thiazolyl, phenyl, pyridinyl,
naphthalenyl, quinolinyl, isoquinolinyl;
R5 represents a halogen atom, a cyano group, a group
NR7R8, or a C1-6 alkyl group, a C1-6 alkoxy group, a C1-6
fluoroalkyl group or a C1-6 fluoroalkoxy group;
R6 represents a phenyl, phenyloxy or pyrimidinyloxy
group; it being possible for the group or groups R6
to be substituted by one or more groups R5 identical
to or different from one another;
R7 and R8 represent independently of one another a C1-6
alkyl group;
R2 represents a hydrogen atom or a C1-6 alkyl group;
R3 represents a hydrogen atom or a C1-6 alkyl, C3-7
cycloalkyl or C3-7 cycloalkyl-C1-3 alkylene group;
in the form of a base, addition salt with an acid,
hydrate or solvate.
3. Compound of formula (I) as claimed in claim 1 or 2,
wherein:
m represents an integer 1 or 2;
in the form of a base, addition salt with an acid,
hydrate or solvate.
4. Compound of formula (I) as claimed in any one of

claims 1 to 3, wherein:
n is 2;
o is 2;
in the form of a base, addition salt with an acid,
hydrate or solvate.
5. Compound of formula (I) as claimed in any one of
Claims 1 to 4, wherein:
R1 represents a group R4 optionally substituted by one or
more groups R5 and/or Re;
R4 represents a group selected from an oxazolyl,
isoxazolyl, phenyl or naphthalenyl;
R5 represents a halogen atom, a cyano group, a group
NR7R8, a C1-6 alkyl group, a C1-6 alkoxy group, a C1-6
fluoroalkyl group, or a C1-6 fluoroalkoxy group;
R6 represents a phenyl, phenyloxy or pyrimidinyloxy
group; it being possible for the group or groups R6
to be substituted by one or more groups R5 identical
to or different from one another;
R7 and R8 represent independently of one another a C1-6
alkyl group;
in the form of a base, addition salt with an acid,
hydrate or solvate.
6. Compound of formula (I) as claimed in any one of
Claims 1 to 5, wherein:
R2 represents a hydrogen atom;
R3 represents a hydrogen atom or a C1-6 alkyl group;
in the form of a base, addition salt with an acid,

hydrate or solvate.
7. Process for preparing a compound of formula (I) as
claimed in any one of claims 1 to 6, comprising the step
consisting in converting the oxazolidine-dione of general
formula (II))

in which A, B, G, R1, R2, m, n and o are as defined in
the formula (I) as claimed in Claim 1 by aminolysis
using an amine of general formula R3NH2 in which R3 is as
defined in the formula (I) as claimed in claim 1.
8. Process for preparing a compound of formula (I) as
claimed in any one of claims 1 to 6, comprising the step
consisting in converting the carbamate-amide derivative
of general formula (Ia)

in which B, R2, R3, n and o are as defined in the formula
(I) as claimed in claim 1,
by reaction with a derivative of general formula (III)
R1—G-[A]m-w (III)
in which W represents a mesylate or tosylate group or a
chlorine, bromine or iodine atom and m, G, A and R1 are

as defined in the formula (I) as claimed in Claim 1.
9. Compound of the general formula (IIa)

in which A, B, G, R1, R2, m, n and o are as defined in
the formula (I) as claimed in claim 1,
with the exception of 3-[1-(phenylmethyl)-4-piperidinyl]-
2, 4-oxazolidinedione.
10. Compound of the general formula (Ia)

in which B, R2, R3, n and o are as defined in the formula
(I) as claimed in claim 1.
11. Pharmaceutical composition comprising at least one
compound of formula (I) as claimed in any one of Claims
1 to 6, in base, salt, hydrate or pharmaceutically
acceptable solvate form, and, optionally, one or more
pharmaceutically acceptable excipients.
12. Compound of formula (I) as claimed in any one of
Claims 1 to 6, in base, salt, hydrate or pharmaceutically

acceptable solvate form, for its use as a medicinal
product.
13. A pharmaceutical composition comprising a compound of
formula (I) as claimed in any one of Claims 1 to 6, in
base, salt, hydrate or pharmaceutically acceptable
solvate form, which is useful for preventing or treating
a pathology in which endogenous cannabinoids and/or any
other substances metabolized by the enzyme FAAH are
involved.
14. A pharmaceutical composition comprising a compound of
formula (I) as claimed in any one of Claims 1 to 6, in
base, salt, hydrate or pharmaceutically acceptable
solvate form, which is useful for preventing or treating
acute or chronic pain, dizziness, vomiting, nausea,
eating disorders, neurological and psychiatric
pathologies, acute or chronic neurodegenerative diseases,
epilepsy, sleep disorders, cardiovascular diseases, renal
ischemia, cancers, disorders of the immune system,
allergic diseases, parasitic, viral or bacterial
infectious diseases, inflammatory diseases, osteoporosis,
ocular conditions, pulmonary conditions, gastrointestinal
diseases or urinary incontinence.


Derivatives of piperidinyl alkyl carbamates, preparation method thereof on use of same as
FAAH enzyme inhibitors

The invention relates to a compound having general formula (I), wherein:
m - 1 to 4; n represents =1, 2 or 3; o = 1 or 2; A is selected from among one or more X, Y
and/or Z groups; X optionally-substituted methylene; Y = C2-alkenylene, optionally
substituted; Z = C3-7-cycloalkyl; B = covalent bond or C1-6-alkylene; G = covalent bond, O, S,
-CH(OH)-, CO, SO or SO2; R1 represents an aryl- or heteroaryl-type group; R2 = hydrogen or
C1-6-alkyl; R3 = hydrogen, C1-6-alkyl, C3-7-cycloalkyl, C3-7-cycloalkyl-C1-3-alkylene.
The inventive compound takes the form of a base, an acid addition salt, a hydrate or a solvate.
Said compound is suitable for use as FAAH enzyme inhibitors.

Documents:

02332-kolnp-2006-abstract.pdf

02332-kolnp-2006-asignment.pdf

02332-kolnp-2006-claims.pdf

02332-kolnp-2006-correspondence others.pdf

02332-kolnp-2006-description(complete).pdf

02332-kolnp-2006-form-1.pdf

02332-kolnp-2006-form-3.pdf

02332-kolnp-2006-form-5.pdf

02332-kolnp-2006-international publication.pdf

02332-kolnp-2006-international search authority report.pdf

2332-kolnp-2006-abstract 1.1.pdf

2332-KOLNP-2006-ABSTRACT.pdf

2332-KOLNP-2006-AMANDED CLAIMS.pdf

2332-KOLNP-2006-ASSIGNMENT 1.1.pdf

2332-KOLNP-2006-ASSIGNMENT-1.2.pdf

2332-KOLNP-2006-CORRESPONDENCE 1.2.pdf

2332-kolnp-2006-correspondence 1.3.pdf

2332-KOLNP-2006-CORRESPONDENCE-1.1.pdf

2332-KOLNP-2006-CORRESPONDENCE-1.4.pdf

2332-KOLNP-2006-CORRESPONDENCE.pdf

2332-kolnp-2006-description (complete) 1.1.pdf

2332-KOLNP-2006-DESCRIPTION (COMPLETE).pdf

2332-KOLNP-2006-EXAMINATION REPORT.pdf

2332-kolnp-2006-form 1-1.1.pdf

2332-KOLNP-2006-FORM 1.pdf

2332-KOLNP-2006-FORM 13-1.1.pdf

2332-KOLNP-2006-FORM 13.pdf

2332-KOLNP-2006-FORM 18-1.1.pdf

2332-kolnp-2006-form 18.pdf

2332-kolnp-2006-form 2-1.1.pdf

2332-KOLNP-2006-FORM 2.pdf

2332-KOLNP-2006-FORM 3-1.1.pdf

2332-KOLNP-2006-FORM 3.pdf

2332-KOLNP-2006-FORM 5.pdf

2332-KOLNP-2006-GPA.pdf

2332-KOLNP-2006-GRANTED-ABSTRACT.pdf

2332-KOLNP-2006-GRANTED-CLAIMS.pdf

2332-KOLNP-2006-GRANTED-DESCRIPTION (COMPLETE).pdf

2332-KOLNP-2006-GRANTED-FORM 1.pdf

2332-KOLNP-2006-GRANTED-FORM 2.pdf

2332-KOLNP-2006-GRANTED-SPECIFICATION.pdf

2332-kolnp-2006-others 1.2.pdf

2332-KOLNP-2006-OTHERS-1.1.pdf

2332-KOLNP-2006-OTHERS-1.2.pdf

2332-KOLNP-2006-OTHERS.pdf

2332-KOLNP-2006-PETITION UNDER RULE 137.pdf

2332-KOLNP-2006-PETITION UNDER RULR 137 1.1.pdf

2332-KOLNP-2006-REPLY TO EXAMINATION REPORT-1.1.pdf

2332-KOLNP-2006-REPLY TO EXAMINATION REPORT.pdf

2332-KOLNP-2006-TRANSLATED COPY OF PRIORITY DOCUMENT.pdf

abstract-02332-kolnp-2006.jpg


Patent Number 252044
Indian Patent Application Number 2332/KOLNP/2006
PG Journal Number 17/2012
Publication Date 27-Apr-2012
Grant Date 23-Apr-2012
Date of Filing 17-Aug-2006
Name of Patentee SANOFI AVENTIS
Applicant Address 174, AVENUE DE FRANCE F-75013, PARIS
Inventors:
# Inventor's Name Inventor's Address
1 ABOUABDELLAH, AHMED 2 RUE DES EGLANTIERS, FR-94320, THIAIS
2 HOORNAERT CHRISTIAN 49 AVENUE ARISTIDE BRIAND FE-92160, ANTONY
3 JEUNESSE JEAN 6 RUE ANDRE MESSAGER, ER-75018, PARIS
4 ALMARIO GARCIA ANTONIO 26, AVENUE ROGER SALENGRO, FR-92290, CHATENAY MALABRY
PCT International Classification Number A61K 31/4468
PCT International Application Number PCT/FR2005/000452
PCT International Filing date 2005-02-25
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 04/01,952 2004-02-26 France