Anti-atherosclerotic aryl compounds

• US 5,422,373 A
• Filed: 03/23/1993
• Issued: 06/06/1995
• Est. Priority Date: 09/25/1990
• Status: Expired due to Fees

• Current Assignee: Burroughs Wellcome and Co.
• Original Assignee: Burroughs Wellcome and Co.
• Inventors: Franzmann, Karl W.
• Primary Examiner(s): Kumar, Shailendra
• Application Number:
  US08/030,397
• Time in Patent Office: 805 Days
• Field of Search: 564/48, 564/52, 564/56, 514/596, 514/598, 514/824
• US Class Current: 514/598
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07C 217/58 with amino groups and the six-membered aromatic ring, or the condensed ring system containing that ring, bound to the same carbon atom of the carbon chain
• CPC Class Codes: C07C 275/30 being further substituted by halogen atoms, or by nitro or nitroso groups
• CPC Class Codes: C07C 275/34 having nitrogen atoms of urea groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
• CPC Class Codes: C07C 45/71 being hydroxy groups
• CPC Class Codes: C07C 47/575 containing ether groups, groups, groups, or groups
• CPC Class Codes: C07D 317/22 etherified
• CPC Class Codes: C07D 333/28 Halogen atoms

Abstract

Diaryl urea compounds having anti-atherosclerosis activity are disclosed. Preferred compounds include the compounds 1-[4-(1,2-dimethoxyethoxy)benzyl-3-(2,4-dimethoxyphenyl)-l-heptylumea and 1-heptyl-3-(2,4-dimethoxyphenyl)-l-[4-(2-methoxyethoxymethoxy)-benzyl]urea.

Claims

1. A compound of formula I ##STR8## wherein;

Ar is phenyl or naphthyl substituted by one or more atoms or groups independently selected from halogen, C_1-8 alkyl, C_1-8 alkoxy (including cycloalkylalkoxy), said alkyl and/or alkoxy group(s) being optionally substituted by one or more halogen atoms. C_1-8 thioalkyl, aryl, aryloxy and aralkoxy, said aralkoxy group being optionally substituted by alkyl, alkoxy, or hydroxyalkyl;

D is --NH--;

E is --N;

F is --O--;

G is C_5-8 straight or branched alkyl, (4-halophenyl)C_1-3 alkyl, or [4-di(C_1-6 alkyl)aminophenyl]C_1-3 alkyl;

J is C_1-3 alkylene;

X is methylene, --CH₂ CH₂ --, --CH₂ OCH₂ CH₂ --, --CH₂ CH(OCH₃)--, --CH₂ CH-- (OCH₂ CH₃)--, or --CH₂ CH₂ OCH₂ CH₂ --; and

Z is C_1-4 alkoxy;

and physiologically functional derivatives thereof.

3. A method of treating atherosclerosis which comprises the administration of an effective amount of the compound of claim 2 or claim 1.

2. A compound which is selected from the group consisting of

1-[4-(1,2-dimethoxyethoxy)-benzyl]-3-(2,4-dimethoxyphenyl)-1-heptylurea,

1-heptyl-3-(2,4-dimethoxyphenyl)-1-(2-methoxyethoxymethoxy)-benzyl]urea,

1-(2,4-difluoro-6-methoxyphenyl)-3-heptyl-3-[4-(2-methoxyethoxymethoxy)benzyl]urea,

1-(4-chloro-2-ethoxyphenyl)-3-heptyl-3-[4-(2-methoxyethoxymethoxy)benzyl]urea, and

1-(4-chloro-2-trifluoromethylphenyl)-3-heptyl-3-[4-(2-methoxyethoxymethoxy)benzyl]urea.

4. A medicament comprising the compound of claim 2 together with a pharmaceutically acceptable carrier.