title: Novel and potent inhibitors of stearoyl-CoA desaturase-1. Part I: Discovery of 3-(2-hydroxyethoxy)-4-methoxy-N-[5-(3-trifluoromethylbenzyl)thiazol-2-yl]benzamide.
abstract: A series of structurally novel stearoyl-CoA desaturase-1 (SCD-1) inhibitors has been identified by optimizing a hit from our corporate library. Preliminary structure-activity relationship (SAR) studies led to the discovery of the highly potent and orally bioavailable thiazole-based SCD-1 inhibitor, 3-(2-hydroxyethoxy)-4-methoxy-N-[5-(3-trifluoromethylbenzyl)thiazol-2-yl]benzamide (23a).
authors.affiliation: Medicinal Chemistry Research Laboratories I, Daiichi Sankyo Co., Ltd, 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. uto.yoshikazu.pw@daiichisankyo.co.jp
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Uto
authors.forename: Tsuneaki
authors.initials: T
authors.lastname: Ogata
authors.forename: Jun
authors.initials: J
authors.lastname: Harada
authors.forename: Yohei
authors.initials: Y
authors.lastname: Kiyotsuka
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ueno
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Miyazawa
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kurata
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Deguchi
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Watanabe
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takagi
authors.forename: Satoko
authors.initials: S
authors.lastname: Wakimoto
authors.forename: Ryo
authors.initials: R
authors.lastname: Okuyama
authors.forename: Manabu
authors.initials: M
authors.lastname: Abe
authors.forename: Nobuya
authors.initials: N
authors.lastname: Kurikawa
authors.forename: Sayako
authors.initials: S
authors.lastname: Kawamura
authors.forename: Michiko
authors.initials: M
authors.lastname: Yamato
authors.forename: Jun
authors.initials: J
authors.lastname: Osumi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001549:Benzamides / Q000138:chemical synthesis* / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008810:Mice, Inbred C57BL; D008956:Models, Chemical; D013230:Stearoyl-CoA Desaturase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: C545364:3-(2-hydroxyethoxy)-4-methoxy-N-(5-(3-trifluoromethylbenzyl)thiazol-2-yl)benzamide; D001549:Benzamides; D004791:Enzyme Inhibitors; D013844:Thiazoles; D013230:Stearoyl-CoA Desaturase