Quinoline leukotriene antagonists

• US 5,952,347 A
• Filed: 03/10/1998
• Issued: 09/14/1999
• Est. Priority Date: 03/13/1997
• Status: Expired due to Term

• Current Assignee: Merck Sharp & Dohme Corporation (Merck & Co., Inc.)
• Original Assignee: Merck & Co., Inc.
• Inventors: Dufresne, Claude, Baillie, Thomas A., Arison, Byron H., Balani, Suresh K.
• Primary Examiner(s): Huang, Evelyn Mei
• Application Number:
  US09/037,949
• Time in Patent Office: 553 Days
• Field of Search: 546/174, 514/311
• US Class Current: 514/311
• CPC Class Codes: C07D 215/18 Halogen atoms or nitro radicals

Abstract

Compounds of Formula I: ##STR1## are antagonists of the actions of leukotrienes. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating angina, cerebral spasm, glomerular nephritis, hepatitis, endotoxemia, uveitis, and allograft rejection.

Claims

1. A compound of the formula ##STR10## and the individual optical isomers thereof, or a pharmaceutically acceptable derivative thereof.

2. A pharmaceutical composition comprising a thereapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.

3. A method of preventing the actions of leukotriene in a mammal comprising administering to said mammal in need of such treatment a therapeutically effective amount of a compound of claim 1.

4. A method for the treatment or prevention of asthma, allergies or inflammation in a mammal comprising administering to said mammal in need of such treatment a therapeutically effective amount of a compound of claim 1.

5. A process for the preparation of a compound of claim 1 which comprises:

a) reacting a compound of formula 1 ##STR11## wherein R is lower alkyl with dimethylsulfoxide and an electrophile to provide a compound of formula 2;

##STR12## b) reacting a compound of formula 2 with silver nitrate and a base to provide the compound of claim 1.

6. A process for the preparation of the individual diastereomers of a compound of claim 1 which comprises:

(a) separating a diastereomeric mixture of a compound of formula 7;

##STR13## wherein R* is 8-phenylmenthyl;

(b) reacting an individual diastereomer with methanesulfonyl chloride to provide the corresponding mesylate;

(c) reacting the mesylate from step (b) with the dianion of 1-mercaptomethylcyclopropaneacetic acid to provide a compound of formula 8;

##STR14## (d) removing the 8-phenylmenthyl group to provide a compound of claim 1.