Title of Invention

"BENZIMIDAZOLE COMPOUNDS AND ANTIHISTAMINIC COMPOSITIONS CONTAINING THE SAME"

Abstract The present invention relates to benzimidazole compounds of formula in which R1 is hydrogen or a short chain (C1 to C3) hydrocarbon group such as methyl, ethyl, isopropyl, cyclopropyl or vinyl, and R2 is a group selected from the group consisting of CH2OH, COOH, COOR3 and 4,4- dimethyl-2-oxazolunyl, R3 selected from the group consisting of a short chain (C1 to C3) alkyl group such as methyl, ethyl, isopropyl, cyclopropyl or vinyl, and their addition pharmaceutically acceptable salts.
Full Text The present invention relates to a benzimidazole compounds and antihistaminic compositions containing the same.
Object of the Invention
The present invention relates to new benzimidazole derivatives with H1 antihistaminic activity, lacking cardiotoxic effects.
Background of the Invention
The prior art closest to the compounds of the present invention is in Spanish patent No. 9201512 which describes a number of piperidine benzimidazole derivatives with antihistarninic and antiallergic activity of general formula:
(Formula Removed)
The major structural difference between the compounds of the present invention and those of the said patent is the presence of oxygenated functions in the phenyl group substitution. An important pharmacophorous character has moreover been found for these oxygenated functions which consists essentially in a selectivity of action and provides a pharmacological profile distinct from that of other known antihistirnaines. The compounds disclosed in this invention present an almost exclusive H1 antihistaminic pharmacological activity and are therefore devoid of action on other

pharmacological receptors even at doses much higher than the
therapeutic ones. Because of this selectivity in action, they are valuable
instruments in treating allergic-type conditions, particularly allowing
their unrestricted use by persons under any other concomitant medication
whatsoever, and in the case of patients with pathological
cardiocirculatory disturbances.
Description of Che Invention
It has long since been known that histamine plays a very important role
in allergic-type diseases, such as allergic rhinitis, conjunctivitis, urticaria
and asthma; antihistaminic compounds acting at the H^-receptor
histamine level are useful for treating such conditions.
First generation Ht antihistamines presented a number of adverse effects,
such as sedation and dryness of the mouth, resulting from its action on
the central nervous system and colinergic receptors.
The search for molecules that would not cross the haematoencephalic
barrier brought about the displacement of the early antihistamines by
other second generation antihistamines which overcame the side effects
linked to their action on the central nervous system. This new generation
of antihistamines, amongst which noteworthy, due to their extensive use
worldwide, are terfenadine and astemizole, has recently displayed a
negative aspect in the form of dangerous cardiovascular effects,
extending the QT space and ventricular arrhythmia, •which has required
its use to be avoided in those cases in which the patient is prone to
suffering such disturbances or when he is being treated with substances
that may interfere with his metabolism.
Attempts at obtaining safe and efficient Ht antihistamines have
multiplied in recent years and this research has resulted in several recent
patent applications claiming pharmaceutical compositions for treating
allergic diseases containing antihistamines devoid of arrhythmogenic
effects, which is the case of US patent application number 924,156
(3/08/92) and international patent application number 95/00480
(05/01/95).
The present invention relates to a group of new compounds with
benzimidazolic structure having potent selective H, antihistaminic
activity, lacking activity on the central nervous system and on the
cardiovascular system.
The compounds subject of the present invention have the following
general formula:
Me
in which Rj is hydrogen or a short chain hydrocarbon group such as
methyl, ethyl, isopropyl, cyclopropyl or vinyl, and R2 is a group
selected from among CHZOH, COOH, COOR, and 4,4-dimethyl-2-
oxazolinyl, R3 being a short chain alkyl group as previously defined,
and their addition salts with pharmacologically acceptable acids or
bases.
Compounds I in which Rj is a short chain alkyl group and R2 is the
4,4-dimethyl-2-oxazolin3rl group can be conveniently prepared by an
N-alkylation reaction of 2-(4-piperidinyl)-lH-benzimidazole with an
alkylating agent of formula III wherein X is a good leaving group in
nucleophilic substitution reactions such as Cl, Br, I, R4SO2, R2SOj,
etc., in the presence of an inorganic base, such as an alkaline metal
carbonate or bicarbonate within an organic solvent, followed by
another N-alkylation reaction of the resulting benzimidazole IV with
an ether of formula XCH2CH2OR,, wherein X has the meaning given
above and R! is a short chain hydrocarbon group, such as Me, Et, i-Pr,
cyclopropyl, vinyl, etc., in the presence of a hydride or an alkaline
metal carbonate.
Compounds I, in which R! is a short chain alkyl group and R2 is a
carboxyl group, can be conveniently prepared by hydrolysis of the
benzimidazoles la with a mineral acid such as HC1 or H2SO4.
Compounds I in which R! is a short chain alkyl group and Rz is a
COORj group in which R, is a short chain alkyl group, can be prepared
by acid hydrolysis of the benzimidazoles la in the presence of an alcohol
solvent RjOH, in adequate conditions for transesterification.
Compounds I in which R! is a short chain alkyl group and R2 is a
Ct^OH group can be prepared by a reduction of the benzimidazoles Ib
or Ic with a suitable reducing agent, such as aluminium and lithium
hydride.
Compound I in which Rt is a hydrogen and R2 is a 4,4-dimethyl-2-
oxazolinyl group can be prepared by an alkylation of the benzimidazole
IV with ethyl chloroacetate in the presence of a hydride or an alkaline
metal carbonate to yield the ester V, which is then reduced by a reducing
agent such as aluminium and lithium hydride.
Compound I in which R, is a hj'drogen and R2 is a COOH group is
conveniently prepared by hydrolysis with a mineral acid such as HC1 or
H2SO4 of the compound le.
The obtained new benzimidazoles I can be turned into pharmaceutically
acceptable salts by treatment with suitable acids or bases.
Compounds of formula I have useful pharmacological properties. In
particular, they are potent H, antihistamines. This activity was clearly
demonstrated in vitro by blocking the histamine-induced contractions in
the isolated guinea pig ileum (Magnus, Pflilgers, Arch. Ges. Physiol.,
102, 123 (1904); Arunlakshana, O. and Schild, H.O., Br. J. Pharmacol.
14,48-58 (1959)) and in vivo by the capacity to inhibit the increment of
histamine-induced cutaneous capillary permeability in rats (Lefebvre, P.,
Salmon, J., Leconte and Cauwenberge, V.H., C.R. Soc. Biol. 156, 183-
186 (1962); Udaka, K., Takeuchi, Y. and Morat, H.Z., Proc. Soc. Exp.
Biol.Med. 133, 1384-1387(1970)).
Thus, compound Ib (R1=ethyl) proved to be a potent guinea pig ileum
Hreceptor histamine mixed antagonist, with calculated pA2=7.98-8.10
and pD2'=6.50. This same compound inhibited in vivo the increase in
capillary permeability in rats with a DESO close to 2 mg/kg p.o. At doses
of 5 mg/kg p.o. it maintained a significant activity, in excess of 50%, for
at least 6 hours.
These compounds are highly selective in their pharmacological action,
and present no significant anticholinergic activity nor activity on the
central nervous and cardiovascular systems. Thus, compound Ib (Rt=Et)
is not able to antagonize significantly the acetylcholine-induced
contractions in isolated guinea pig ileum at 0.1 M concentrations and
does not modify the spontaneous motor activity of the rat at 100 mg/kg
p.o.; furthermore, this same compound, administered at 20 mg/kg i.v.,
induces no morphological ECG disturbance nor does it increase the QTC
interval in rats.
In view of their useful pharmacological antihistaminic and antiallergic
properties, the compounds described in the present invention can be
formulated in several pharmaceutical forms to be later administered
orally, topically, injectably and rectally. Oral preparations are made by
intimately mixing a quantity effective as antihistaminic of one of the
products described in the present invention with excipients such as
lactose, cellulose, talc and the like for tablets or capsules, or water,
glycols, alcohols, oils and the like for syrups, solutions and suspensions.
Topical administration can be made in the form of creams, ointments,
gels, solutions and transcutaneous plasters, using agents such as
vaseline, polyethylene glycols. etc. as a carrier. In preparations for
injectables, the excipient will be, at least for the most part, sterilised
water, although other excipients, such as saline solutions, glucose
solutions, etc., or mixtures thereof, may be added to enhance solubility.
The examples detailed below illustrate the present invention without
howsoever limiting its scope.
Example 1
Preparation of l-(2-ethoxyethyl)-2-[l-(2-(4-(l-(4.4-dimethyl-A*-
oxazoline-2-yl)-l-(methylethyl)phenyl)ethyl)piperidine-4-yl]-lH -
benzimidQTfQlp-. (la, R1=Et)
3.57 g of sodium carbonate were added to a suspension of 14 g 2-(4-(l-
(4,4-dimethyl-A 2-oxazoline-2-yl)-1 -methylethyl)phenyl)ethyl p-toluenesulpohate
and 6.78 g 2-(4-piperidinyl)-lH-benzimidazole in 60 ml of
DMF and the resulting suspension was heated at 80° for 14 hours. The
DMF was concentrated and the reaction mass was poured onto water/ice
whereupon a solid crystallised which was filtered, washed with water
and dried at 50°C to yield 10 g of 2-[l-(2-(4-(l-(4,4-dimethyl-A2-
oxazoline-2-yl)-1 -methylethyl)phenyl)ethyl)piperidine-4-yl] 1H
benzimidazole. The resulting solid was dissolved in 25 ml of DMF and
1.2 g of a sodium hydride in 60% oil suspension was added to this. The
resulting suspension was stirred at room temperature for two hours and
2.44 g of 2-chloroethylethylether were added. The reaction mass was
heated at 80°C for 16 hours, cooled, poured on water/ice, extracted with
ether and washed with water and with saturated sodium chloride
solution. The ethereal solution was dried over anhydrous sodium
sulphate and concentrated to yield 11.2 g of 1 -(2-ethoxyethyl)-2-[ 1 -(2-(4-
(1 -(4,4-dimethyl-A2-oxazolme-2-yl)-l -methylethyl)phenyl)ethyl )
piperidine-4 -yl] -1 H-benzimidazole.
MP: 98-100°C (ethanol).
RMN-'H (CDClj), 6: 1.1 (t, 3H); 1.3 (s, 6H); 1.5 (s, 6H), 1.9 (m, 2H);
2.1 (m, 4H); 2.6 (t, 2H); 2.8 (t, 2H); 3.0 (m, 1H); 3.1 (d, 2H); 3.4 (c,
2H); 3.7 (t, 2H); 3.9 (s, 2H); 4.3 (t, 2H); 7.1-7.3 (m, 7H); 7.7-7.8 (m,
1H).
RMN-13C (CDClj), 6: 14.96; 27.38; 28.15; 31.06; 33.10; 34.53; 40.18;
43.60; 53.71; 60.46; 66.74; 66.83; 68.59; 79.14; 109.09; 119.41;
121.71; 121.88; 125.30; 128.73; 134.78; 138.72; 142.72; 143.04; 158.41
and 177.70.
Example 2
Preparation of 2-[4-(2-(4-(l-(2-ethoxyethyl)benzimidazole-2-yl)
piperidine-l-yl)ethy(}phenyl]-2-methylpropanoic acid. (Ib, R,=Et)
6.72 g of l-(2-eihoxyethyl)-2-[l-(2-(4-(l-(4,4-dimethyl-A2-oxazoline-2-
yl)-1 -methylethyl)phenyl)ethyl)piperidine-4-yl]-1 H-benzimidazole (la)
were dissolved in 170 ml of HC1 3N and refiuxed for an hour. This was
cooled and taken to pH 7 with 50% sodium hydroxide. The solution was
extracted with «-butanol, washed with water, dried over anhydrous
sodium sulphate and concentrated. Methanol (30 ml) and 50% sodium
hydroxide (40 ml) were added to the residue and refiuxed for thirty
minutes. The methanol was distilled off and water was added until
dissolution was complete. This was extracted with ether and the aqueous
layer was taken to pH 7 with 20% HC1 and saturated with sodium
chloride, whereupon a solid precipitated which was filtered, washed
repeatedly with water and dried in a vacuum dryer at 50°C to yield 3.5
g of 2-[4-(2-(4-(l-(2-ethoxyethyf) benzimidazole-2-yl)piperidine-lyl)
ethyl) phenyl]-2-methylpropanoic acid.
MP: 199-201°C
RMN-'H (DMSO-da), 6: 1.0 (t, 3H); 1.4 (s, 6H); 1.8 (m, 4H), 2.2 (m,
2H); 2.5 (t, 2H); 2.7 (t, 2H); 3.0 (m, 3H); 3.3 (c, 2H); 3.6 (t, 2H); 4.4 (t,
2H); 7.0-7.3 (m, 6H); 7.4-7.6 (m, 2H).
KMN-1JC (DMSO-da), 6: 14.90; 26.59; 30.97; 32.22; 33.39; 43.04;
45.50; 53.08; 60.05; 65.70; 68.43; 110.18; 118.40; 121.16; 121.35;
125.47; 128.42; 134.72; 138.33; 142.29; 143.03; 158.60; and 177.87.
Example 3
Preparation of ethyl 2-[4-(2- (4- (1- (2-ethox\'ethyl)benzimidazole-2-yl)
piperidme-l-yl-)e1]^yl)pher^yl]-2-methylpropanoate. (Ic, R^ET, Rj=ET)
Concentrated sulphuric acid (20 ml) were added over a solution of 10 g
of 1 -(2-ethoxyethyl)-2-[ 1 -(2-(4-(l-(4.4-dimemyl-A 2-oxazoline-2-yl)-l -
methylethyl)phenyl)ethyl)piperidine-4-yl]-lH-benzimidazole in 250 ml
of ethanol, and this was refluxed for 16 hours. This was cooled and 1
litre of ether was added. The organic layer was separated and washed
with water, 10% sodium bicarbonate solution and once again with water.
This was dried over anhydrous sodium sulphate and concentrated to
yield 7 g of an oil which was purified by flash-chromatography using a
95/5 cMoroform/ethanol mixture as eluent to yield 5 g of ethyl 2-[4-(2-(4-
(1 -(2-ethoxyethyl) benzimidazole-2-yl)piperidine-1 -yl)ethyl)phenyl]-2-
methylpropanoate in the form of an oil.
RMM-'H (CDClj), 6: 1.1 (t, 3H); 1.2 (t, 3H); 1.5 (s, 6H); 2.0 (m, 2H);
2.2 (m, 4H); 2.6 (t, 2H); 2.8 (t, 2H); 3.0 (m, 1H); 3.2 (m, 2H); 3.4 (c,
2H); 3.7 (t, 2H); 4.1 (c, 2H); 4.3 (t, 2H); 7.1-7.3 (m, 7H); 7.6-7.7 (m,
1H).
RMN-1JC (CDC13), 6: 13.86; 14.80; 26.35; 30.62; 32.73; 33.87; 43.48;
45.91; 53.26; 60.11; 60.49; 66.61; 68.40; 109.02; 119.16; 121.55;
121.75; 125.40; 128.50; 134.56; 138.40; 142.29; 142.51; 158.13 and
176.53.
Example 4
Preparation of l-(2-ethoxyethyl)-2-[l-(2-(4-(l, l-dimefhyl-2-hydroxyethyl)
phenyl)ethyl)piperidine-4-yl]-lH-benzimidazole. (Id, Rt=Et)
1 g of aluminium and lithium hydride was dissolved in 30 ml of THF
and 3 g of ethyl 2-[4-(2-(4-(l-(2-ethokyethyl)benzimidazole-2-yl)
piperidine-l-yl)ethyl)phenyl]-2-methylpropanoate were added dropwise
thereto. This was stirred for four hours at room temperature and some
millilitres of Water were added to eliminate excess hydride. The solution
was filtered and the filtrate was washed with a saturated sodium chloride
solution. This was dried and concentrated. The residue was redissolved
in chloroform and washed with water, dried and concentrated. The
residue was purified by flash-chromatography using a
hexane/ether/isopropyl-amine mixture (2/7.5/0.5) as an eluent, to yield
1:5 g of l-(2-ethoxyethyl)-2-[l-(2-(4-(l,l-dimethyl-2-hydroxyethyl)
phenyl)ethyl)piperidine-4 -yl] -1 H-benzimidazole.
MP: 112-114°C
RMN-'H (CDC13), 6: 1.0 (t, 3H); 1.4 (s, 6H); 1.9-2.1 (m, 2H); 2.1-2.3
(m, 4H); 2.6 (t, 2H); 2.8 (t, 2H); 3.0 (m, 1H); 3.2 (d, 2H); 3.4 (c, 2H);
3.6 (s, 2H); 3.7 (t, 2H); 4.3 (t, 2H); 7.1-7.4 (m, 7H); 7.8 (m, 1H).
RMN-UC (CDClj), 6: 15.01; 25.34; 31.07; 33.07; 34.53; 39.78; 43.64;
53.72; 60.52; 66.88; 68.62; 73.07; 109.13; 119.44; 121.77; 121.94;
126.22; 128.80; 134.78; 138.39; 142.71; 143.90; 158.45.
Example 5
Preparation of l-(2-hydroxyethyl)-2-[l-(2-(4-(l-(4.4-dimethyl-Aoxazo
line-2-y 1) -1-me thyle thyl)phenyl) e thyl)piperidine-4-yl] - Iff -
benzitnidazole. (le)
5g of 2-[l-(2-(4-(l-(454-dimethyl-Aa-oxazoline-2-yl)-l-methylethyl)
phenyl)piperidine-4-yl]-lH-benzimidazole were dissolved in 3O ml of
DMF and 0.54 g of a sodium hydride in oil suspension were added
thereto. The resulting suspension was stirred for two hours at room
temperature and 1.19 ml of ethyl chloroacetate were added dropwise. The
reaction mass was heated at 70° for 16 hours, cooled and poured on 300
ml of water. This was extracted with ether and the ethereal layer was
washed with water, dried over anhydrous sodium sulphate and filtered.
0.8 g of aluminium and lithium hydride were dissolved in 30 ml of ether
and the previously filtered ethereal phase was added dropwise to this
solution. This was stirred for 4 hours at room temperature, and 20 ml of
a 10% sodium hydroxide solution were added thereto. This was saturated
with sodium chloride and the ethereal layer was separated. The aqueous
phase• was extracted with ether. The ethereal phase*s were all blended
together and washed with water and with a saturated sodium chloride
solution. This was dried over anhydrous sodium sulphate, and
concentrated to yield 2.6 g of l-(2-hydroxyethyl)-2-[l-(2-(4-(l-(4,4-
dimethyl-A 2-oxazoline-2-yl)-1 -methylethyl)phenyl)ethyl)piperidine-4 -yl] -
1 H-benzimidazole in the form of an oil.
RMN-'H (CDC1,), 6: 1.3 (s, 6H); 1.6 (s, 6H); 1.8-2.2 (m, 6H); 2.6 (t,
2H); 2.8 (t, 2H); 2.9 (m, 1H); 3.0-3.1 (m, 2H); 3.7 (s, 2H); 4.0 (s 2H);
4.3 (t, 2H); 7.1-7.4 (m, 7H); 7.7 (m, 1H).
KMN-"C (CDC1,), 6: 15.01; 25.34; 31.07; 33.07; 34.53; 39.78; 43.64;
53.72; 60.52; 66.88; 68.62; 73.07; 109.13; 119.44; 121.77; 121.94;
126.22; 128.80; 134.78; 138.39; 142.71; 143.90; 158.45.
Example 6
Preparation of 2-[4-(2-(4-(l-(2-hydroxyefhyl)benzimidazole-2-yl)
piperidine-1 -yl)ethyl)phenyl]-2-methylpropanoic acid. (If)
5 g of l-/2-hydroxyethyl)-2-[l l-m^e1iiylethyl)phenyl)ethyl)piperidine-4-yl]-lH-ben7irTiidazole (le) were
dissolved in 45 ml of 3N HC1 and refluxed for an hour. This was taken
to a basic pH with 50% NaOH and 2O ml of ethylene glycol were added.
This was heated at 190°C for three hours with simultaneous distillation
and then concentrated in vacuo. Water was added and extracted with
ether. The aqueous layer was taken to pH 7 with diluted HC1, saturated
with sodium chloride and extracted with H-butanol. The ethereal extract
was. dried and concentrated. The residue was recrystallised in
acetone/methanol to yield 2.7 g of 2-[4-(2-(4-(l-(2-hydroxyethyl)
benzimidazole-2-yl)piperidine-1 -yl)ethyl)phenyl]-2-methylpropanoic
acid.
MP: 218°C (breaks down)
RMN-'HCCDClj), 6: 1.4 (sf 6H); 2.0-2.1 (m, 4H); 2.7-2.9 (m, 4H); 2.9-
3.1 (t, 2H); 3.2-3.5 (m, 3H); 3.7 (t, 2H); 4.3 (t, 2H); 6.9-7.1 (m, 2H); 7.1-
7.2 (m, 2H); 7.2-7.3 (m, 2H); 7.3-7.4 (m, 1H); 7.4-7.5 (m, 1H).






WE CLAIM:
1. Benzimidazole compounds of formula
(Formula Removed)
in which R1 is hydrogen or a short chain (C1 to C3) hydrocarbon group such as methyl, ethyl, isopropyl, cyclopropyl or vinyl, and R2 is a group selected from the group consisting of CH2OH, COOH, COOR3 and 4,4-dimethyl-2-oxazolunyl, R3 selected from the group consisting of a short chain (C1 to C3) alkyl group such as methyl, ethyl, isopropyl, cyclopropyl or vinyl, and their addition pharmaceutically acceptable salts.
2. A compound as claimed in claim 1 which is l-(2-ethoxyethyl)-2-[l-(2-(4-
(l-(4,4-dimethyl-2-oxazoline-2-yl)-l-methylethyl)phenyl)ethyl)piperidine-
4-yl] -lH-benzimidazole.
3. A compound as claimed in claim 1 which is 2-[4-(2-(4-(l-(2-
ethoxyethyl)benzimidazole-2-yl)piperidine-1 -yl)ethyl)phenyl]-2-methylpropanoic acid.
4. A compound as claimed in claim 1 which is ethyl 2-[4-(2-(4-(l-(2-ethoxyethyl) benzimidazole - 2 -yl) piperidine -1 -yl) ethyl) phenyl] - 2 -methylpropanoate.
5. A compound as claimed in claim 1 which is l-(2-ethoxyethyl)-2-[l-(2-(4-(1,1 -dimethyl-2-hydroxyethyl)phenyl)ethyl)piperidine-4-yl]- 1H-benzimidazole.
6. A compound as claimed in claim 1 which is l-(2-hydroxyethyl)-2-[l-(2-(4-(1 - (4,4-dimethyl-2-oxazoline - 2-yl) -1-methylethyl) phenyl) ethyljpiperidine-4-yl] -1 H-benzimidazole.
7. A compound as claimed in claim 1 which is 2-[4-(2-(4-(l-(2-hydroxyethyl)benzimidazole-2-yl)piperidine-1 -yl) ethyl) phenyl] -2-methylpropanoic acid.

Documents:

1071-DEL-2000-Abstract-(16-03-2009).pdf

1071-DEL-2000-Abstract-(27-11-2008).pdf

1071-del-2000-abstract.pdf

1071-DEL-2000-Claims-(16-03-2009).pdf

1071-del-2000-claims.pdf

1071-del-2000-complete specification (granted).pdf

1071-DEL-2000-Correspondence-Others-(16-03-2009).pdf

1071-DEL-2000-Correspondence-Others-(27-11-2008).pdf

1071-del-2000-correspondence-others.pdf

1071-del-2000-correspondence-po.pdf

1071-DEL-2000-Description (Complete)-(16-03-2009).pdf

1071-del-2000-description (complete)-(25-03-2009).pdf

1071-DEL-2000-Description (Complete)-(27-11-2008).pdf

1071-del-2000-description (complete).pdf

1071-DEL-2000-Form-1-(16-03-2009).pdf

1071-DEL-2000-Form-1-(27-11-2008).pdf

1071-del-2000-form-1.pdf

1071-del-2000-form-13-(27-11-2008)..pdf

1071-del-2000-form-13.pdf

1071-del-2000-form-18.pdf

1071-DEL-2000-Form-2-(16-03-2009).pdf

1071-DEL-2000-Form-2-(27-11-2008).pdf

1071-del-2000-form-2.pdf

1071-DEL-2000-Form-3-(27-11-2008).pdf

1071-del-2000-form-3.pdf

1071-del-2000-form-5.pdf

1071-DEL-2000-GPA-(27-11-2008).pdf

1071-del-2000-gpa.pdf

1071-DEL-2000-Petition-137-(27-11-2008).pdf

1071-del-2000-petition-138.pdf

1071-DELNP-2000-Abstract-(25-03-2009).pdf

1071-DELNP-2000-Claims-(25-03-2009).pdf

abstract.jpg


Patent Number 233119
Indian Patent Application Number 1071/DEL/2000
PG Journal Number 13/2009
Publication Date 27-Mar-2009
Grant Date 26-Mar-2009
Date of Filing 28-Nov-2000
Name of Patentee FABRICA ESPANOLA DE PRODUCTOS QUIMICOS Y FARMACEUTICOS, S.A. (FAES)
Applicant Address MAXIMO AGUIRRE, NO. 14, 48940 LEJONA, VIZCAYA, SPAIN.
Inventors:
# Inventor's Name Inventor's Address
1 AURELIO ORJALES PASEO DEL PUERTO 24, 48990 NEGURI, (VIZEAYA), SPAIN.
2 VICTOR RUBIO C/ BIZKERRE, 30-1OC, 48990 GETXO, (VIZCAYA), SPAIN.
3 MARAVILLAS BORDELL C/ MAIATZAREN BATA, 2-4OC, 48940 LEIQA, (VIZCAYA), SPAIN.
PCT International Classification Number C07D 401/04
PCT International Application Number N/A
PCT International Filing date
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 P 960 1236 1996-06-04 Spain