title: Benzimidazoles as non-peptide luteinizing hormone-releasing hormone (LHRH) antagonists. Part 3: Discovery of 1-(1H-benzimidazol-5-yl)-3-tert-butylurea derivatives.
abstract: 1-(1H-Benzimidazol-5-yl)-3-tert-butylurea derivatives have been identified as a novel class of non-peptide luteinizing hormone-releasing hormone (LHRH) antagonists. Herein, we disclose the synthesis and structure-activity relationships (SAR) of this class resulting in the identification of compound 12c, with dual functional activity on human and rat receptors (rat LHRH: IC50=120 nM; human LHRH: IC50=18 nM). These SAR studies suggest that 1-(1H-benzimidazol-5-yl)-3-tert-butylurea is a new pharmacophore for small molecule LHRH antagonists.
authors.affiliation: Department of Chemistry, Research Center Kyoto, Bayer Yakuhin, Ltd, Kizu, Soraku, Kyoto 619-0216, Japan. miyuki.tatsuta@pfizer.com
authors.forename: Miyuki
authors.initials: M
authors.lastname: Tatsuta
authors.forename: Mikayo
authors.initials: M
authors.lastname: Kataoka
authors.forename: Kayo
authors.initials: K
authors.lastname: Yasoshima
authors.forename: Sachiko
authors.initials: S
authors.lastname: Sakakibara
authors.forename: Yuka
authors.initials: Y
authors.lastname: Shogase
authors.forename: Makoto
authors.initials: M
authors.lastname: Shimazaki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yura
authors.forename: Yingfu
authors.initials: Y
authors.lastname: Li
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Jang
authors.initials: J
authors.lastname: Gupta
authors.forename: Klaus
authors.initials: K
authors.lastname: Urbahns
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D015394:Molecular Structure; D051381:Rats; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D001562:Benzimidazoles; D007987:Gonadotropin-Releasing Hormone; D014508:Urea