title: The identification of substituted benzothiophene derivatives as PGE(2) subtype 4 receptor antagonists: From acid to non-acid.
abstract: We disclose herein our preliminary SAR study on the identification of substituted benzothiophene derivatives as PGE(2) subtype 4 receptor antagonists. A potent EP(4) antagonist 6a (K(i)=1.4nM with 10% HSA) was identified. Furthermore, we found that an acidic group was not essential for the EP(4) antagonizing activity in the series and neutral replacements were identified. This opens a new direction for future EP(4) antagonist design.
authors.affiliation: Department of Medicinal Chemistry, Merck Frosst Centre for Therapeutic Research, 16711 Trans Canada Hwy., Kirkland, Québec, Canada H9H 3L1. lianhai_li@merck.com
authors.forename: Lianhai
authors.initials: L
authors.lastname: Li
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Mathieu
authors.forename: Danielle
authors.initials: D
authors.lastname: Denis
authors.forename: Alex G
authors.initials: AG
authors.lastname: Therien
authors.forename: Zhaoyin
authors.initials: Z
authors.lastname: Wang
mesh_terms: D002460:Cell Line; D006801:Humans; D011485:Protein Binding; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D058309:Receptors, Prostaglandin E, EP4 Subtype; D013876:Thiophenes; C088015:benzothiophene