Structure-activity relationships (SAR) and structure-kinetic relationships (SKR) of bicyclic heteroaromatic acetic acids as potent CRTh2 antagonists I

Bioorg Med Chem Lett. 2014 Nov 1;24(21):5118-22. doi: 10.1016/j.bmcl.2014.09.005. Epub 2014 Oct 15.

Abstract

A knowledge-based design strategy led to the discovery of several new series of potent and orally bioavailable CRTh2 antagonists where a bicyclic heteroaromatic ring serves as the central core. Structure-kinetic relationships (SKR) opened up the possibility of long receptor residence times.

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

MeSH terms

  • Acetates / chemical synthesis
  • Acetates / chemistry*
  • Acetates / pharmacokinetics
  • Animals
  • Bridged Bicyclo Compounds / chemistry*
  • Half-Life
  • Humans
  • Hydrogen-Ion Concentration
  • Microsomes, Liver / metabolism
  • Rats
  • Receptors, Immunologic / antagonists & inhibitors*
  • Receptors, Immunologic / metabolism
  • Receptors, Prostaglandin / antagonists & inhibitors*
  • Receptors, Prostaglandin / metabolism
  • Solubility
  • Structure-Activity Relationship

Substances

  • Acetates
  • Bridged Bicyclo Compounds
  • Receptors, Immunologic
  • Receptors, Prostaglandin
  • prostaglandin D2 receptor