Structure-activity relationships (SAR) and structure-kinetic relationships (SKR) of sulphone-based CRTh2 antagonists

Abstract

Monocyclic and bicyclic ring systems were investigated as the "core" section of a series of diphenylsulphone-containing acetic acid CRTh2 receptor antagonists. A range of potencies were observed and single-digit nanomolar potencies were obtained in both the monocyclic and bicyclic cores. Residence times for the monocyclic compounds were very short. Some of the bicyclic cores displayed better residence times. A methyl group in the northern part of the core, between the head and tail was a necessary requirement for the beginnings of long residence times. Variations of the tail substitution maximised potencies and residence times.

Keywords: CRTh2 antagonist; Receptor residence time; Structure-activity relationship (SAR); Structure-kinetic relationship (SKR).