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.
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.
Actelion Pharmaceuticals Ltd, Gewerbestrasse, 16, CH-4123 Allschwil, Switzerland.
Julien
J
Pothier
Markus A
MA
Riederer
Oliver
O
Peter
Xavier
X
Leroy
Anja
A
Valdenaire
Carmela
C
Gnerre
Heinz
H
Fretz
D000085:Acetates / Q000737:chemistry* / Q000494:pharmacology; D001554:Benzene / Q000737:chemistry*; D006801:Humans; D007093:Imidazoles / Q000737:chemistry*; D015394:Molecular Structure; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000737:chemistry*
D000085:Acetates; D007093:Imidazoles; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D013438:Sulfhydryl Compounds; C029899:imidazole; D001554:Benzene; C036293:prostaglandin D2 receptor