Ethynylthiazole derivative leukotriene antagonists

Abstract

This patent discloses ethynylthiazole derivatives which exhibit potent activity as antagonists of peptidoleukotriene receptors, and as such, would be expected to be useful as treatment of allergic diseases such as asthma and cystic fibrosis. The key feature of the molecules encompassed by this application which differentiates them from previously described and closely related leukotriene (LT) antagonists is the alkynyl linking group designed to impart photostability to the series. The preferred compound claimed by the application (1) is reported to have very potent activity both in vitro (Ki = 0.46 nM) and in vivo (p.o. ID50 = 0.025 mg/kg). As photostability is a key component of the invention, comparative data are provided for the preferred compound and an example of an alkenyl-linked analogue.