# US 5,705,523 A · Pyridine- and imidazole-derived agents for cardiovascular diseases

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- Number: US 5,705,523 A
- Document ID: US5705523A
- Status: Granted
- Kind: A
- Application number: 08/502,748
- Filed: 1995-07-14
- Granted: 1998-01-06
- Earliest claimed: 1991-04-04
- Assignees: Pfizer Inc.
- Inventors: Roger Peter Dickinson; Kevin Neil Dack; John Steele
- Web page: https://patentgrep.com/patent/US5705523A

## CPC

- C07D 231/12: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- A61P 7/02: Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 213/55: Acids; Esters
- C07D 213/65: attached in position 3 or 5
- C07D 233/56: with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C07D 249/08: 1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D 401/12: linked by a chain containing hetero atoms as chain links
- C07D 409/12: linked by a chain containing hetero atoms as chain links
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Compounds of formula: ##STR1## or a biolabile ester thereof, or a pharmaceutically acceptable salt of either, wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are each independently selected from H or C.sub.1 -C.sub.4 alkyl; R.sup.5 is (CH.sub.2).sub.m SO.sub.2 R.sup.6, (CH.sub.2).sub.m NHSO.sub.2 R.sup.6 or (CH.sub.2).sub.m NHCOR.sup.7 ; R.sup.6 and R.sup.7 are C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.3 perfluoroalkyl-(CH.sub.2).sub.n, C.sub.3 -C.sub.6 cycloalkyl(CH.sub.2).sub.n, aryl(CH.sub.2).sub.n or heteroaryl(CH.sub.2).sub.n ; or R.sup.6 is NR.sup.8 R.sup.9 ; R.sup.8 is H or C.sub.1 -C.sub.4 alkyl; R.sup.9 is C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 cycloalkyl(CH.sub.2).sub.n, aryl(CH.sub.2).sub.n or heteroaryl(CH.sub.2).sub.n ; or R.sup.8 and R.sup.9 together with the nitrogen atom to which they are attached from a 5- to 7-membered heterocyclic ring; X is CH.sub.2, CHCH.sub.3, C(OH)CH.sub.3, C.dbd.CH.sub.2 or O; m is 0 or 1; n is 0, 1, 2 or 3; and Het is 3- or 4-pyridyl or 1-imidazolyl; are combined thromboxane A.sub.2 synthetase inhibitors and thromboxane A.sub.2 /endoperoxide antagonists of utility in the treatment of disease conditions in which thromboxane A.sub.2 is a causative agent.

## Claims

### Claim 1

A compound of formula: ##STR22## or a (C.sub.1 -C.sub.4)alkyl ester thereof, or a pharmaceutially acceptable salt of either,
wherein
R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are each independently selected from H for C.sub.1 -C.sub.4 alkyl;
R.sup.5 is (CH.sub.2).sub.m SO.sub.2 R.sup.6, (CH.sub.2).sub.m NHSO.sub.2 R.sup.6 or (CH.sub.2).sub.m NHCOR.sup.7 ;
R.sup.6 and R.sup.7 are C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.3 perfluoroalkyl(CH.sub.2).sub.n, C.sub.3 -C.sub.6 cycloalkyl(CH.sub.2).sub.n or aryl (CH.sub.2).sub.n ; or
R.sup.6 is NR.sup.8 R.sup.9 ;
R.sup.8 is H or C.sub.1 -C.sub.4 alkyl;
R.sup.9 is C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 cyoloalkyl(CH.sub.2).sub.n or
aryl(CH.sub.2).sub.n ;
X is CH.sub.2 or CHCH.sub.3 ;
m is 0 or 1;
n is 0, 1, 2 or 3; and
Het is 1-imidazolyl.

### Claim 2 (depends on 1)

A compound as claimed in claim 1 wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are each independently selected from H or methyl; R.sup.5 is CH.sub.2 SO.sub.2 phenyl, SO.sub.2 phenyl, NHCOCH.sub.2 CH(CH.sub.3).sub.2, NHCOphenyl, CH.sub.2 NHSO.sub.2 (4-chlcrophenyl) or NHSO.sub.2 R.sup.6 ; R.sup.6 is C.sub.1 -C.sub.5 alkyl, CH.sub.2 CF.sub.3, cyclohexyl, phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-methylphenyl or NR.sup.8 R.sup.9 ; R.sup.8 is H, methyl or ethyl; and R.sup.9 is methyl, ethyl or 4-chlorophenyl.

### Claim 3 (depends on 1)

A compound of formula: ##STR23## wherein X is CH.sub.2 or CHCH.sub.3 and Het is 1-imidazolyl, R.sup.10 is C.sub.1 -C.sub.4 alkyl, and R.sup.1, R.sup.2, R.sup.3, R.sup.4 and m are as defined in claim 1.

### Claim 4 (depends on 1)

A compound of formula: ##STR24## wherein X is CH.sub.2 or CHCH.sub.3 and Het is 1-imidazolyl, R.sup.10 is C.sub.1 -C.sub.4 alkyl, and R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.6 and m are as defined in claim 1.

### Claim 5 (depends on 1)

A pharmaceutical composition comprising a compound of formula (I) or a C.sub.1 -C.sub.4)alkyl ester thereof, or a pharmaceutically acceptable salt of either, as claimed in claim 1, together with a pharmaceutically acceptable diluent or carrier.

### Claim 6 (depends on 1)

A method of treating or preventing atherosclerosis, unstable angina, reocclusion post-percutaneous transluminal coronary and femoral angioplasty, myocardial infarction, stroke, cardiac arrhythmias, transient ischaemic attack or peripheral vascular disease in a mammal which comprises administering to said mammal a therapeutically effective amount of a compound of formula (I), or a (C.sub.1 -C.sub.4)alkyl ester thereof, or a pharmaceutically acceptable salt of either, or a pharmaceutical composition containing any of these entities, as claimed in claim 1.