Novel 2-(2-(benzylthio)-1H-benzo[d]imidazol-1-yl)acetic acids: discovery and hit-to-lead evolution of a selective CRTh2 receptor antagonist chemotype

Julien Pothier; Markus A Riederer; Oliver Peter; Xavier Leroy; Anja Valdenaire; Carmela Gnerre; Heinz Fretz

doi:10.1016/j.bmcl.2012.05.087

Novel 2-(2-(benzylthio)-1H-benzo[d]imidazol-1-yl)acetic acids: discovery and hit-to-lead evolution of a selective CRTh2 receptor antagonist chemotype

Bioorg Med Chem Lett. 2012 Jul 15;22(14):4660-4. doi: 10.1016/j.bmcl.2012.05.087. Epub 2012 Jun 1.

Authors

Julien Pothier¹, Markus A Riederer, Oliver Peter, Xavier Leroy, Anja Valdenaire, Carmela Gnerre, Heinz Fretz

Affiliation

¹ Actelion Pharmaceuticals Ltd, Gewerbestrasse, 16, CH-4123 Allschwil, Switzerland.

PMID: 22726929
DOI: 10.1016/j.bmcl.2012.05.087

Abstract

Hit-to-lead evolution of 2-(2-((2-(4-chlorophenoxy)ethyl)thio)-1H-benzo[d]imidazol-1-yl)acetic acid (1), discovered in a high-throughput screening campaign as a novel chemotype of CRTh2 receptor antagonist, is presented. SAR development as well as in vitro and in vivo DMPK properties of selected representatives of substituted 2-(2-(benzylthio)-1H-benzo[d]imidazol-1-yl)acetic acids are discussed.

MeSH terms

Acetates / chemistry*
Acetates / pharmacology
Benzene / chemistry*
Humans
Imidazoles / chemistry*
Molecular Structure
Receptors, Immunologic / antagonists & inhibitors*
Receptors, Prostaglandin / antagonists & inhibitors*
Structure-Activity Relationship
Sulfhydryl Compounds / chemistry*

Substances

Acetates
Imidazoles
Receptors, Immunologic
Receptors, Prostaglandin
Sulfhydryl Compounds
imidazole
Benzene
prostaglandin D2 receptor