PGD2 receptor antagonists for the treatment of inflammatory diseases

Abstract

Disclosed herein are compounds represented by Structural Formula (I): (I), wherein the variables are defined herein. Also disclosed is the use of such compounds for inhibiting the G-protein coupled receptor referred to as chemoattractant receptor-homologous molecule expressed on Th2 (“CRTH2”) for the treatment of inflammatory disorders.

Description

CROSS REFERENCE TO RELATED APPLICATIONS [0001] This application is a continuation of U.S. patent application Ser. No. 10 / 678,872, filed Oct. 3, 2003, which claims the benefit of U.S. Provisional Application No. 60 / 416,501, filed Oct. 4, 2002, now abandoned. Each of these applications is hereby incorporated in its entirety by reference herein.BACKGROUND OF THE INVENTION [0002] PGD2 belongs to the class of prostaglandins derived from arachidonic acid. It is the predominant prostanoid produced by activated mast cells and is involved in the pathogenesis of allergic diseases such as asthma, rhinitis and atopic dermatitis (see Lewis et al. J. Immunol. 129:1627 (1982), Hardy et al., N. Eng. J. Med. 311: 209 (1984), Murray et al., N. Eng. J. Med. 315: 800 (1986), Barry et al., Br. J. Pharmacol. 94:773 (1988). PGD2 is a ligand for the DP receptor and was initially thought to elicit all its biological actions through this receptor. The role of the DP receptor in allergic asthma has been demon...

AI Technical Summary

Benefits of technology

[0003] It has now been found that certain 1,2,3,4-tetrahydro-quinolin-4-yl-amines are potent inhibitors of CRTH2. For example, many compounds effectively inhibited the binding of PGD2 to HEK-293 cells which stably express CRTH2...

Problems solved by technology

Unfortunately, there are few if any known CRTH2 inhibitors.

As a consequence, clinicians will be unable to exploit these discoveries until new CRTH2 inhibitors are developed.

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