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.
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).
Uto
Yoshikazu
Y
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
Ogata
Tsuneaki
T
Harada
Jun
J
Kiyotsuka
Yohei
Y
Ueno
Yuko
Y
Miyazawa
Yuriko
Y
Kurata
Hitoshi
H
Deguchi
Tsuneo
T
Watanabe
Nobuaki
N
Takagi
Toshiyuki
T
Wakimoto
Satoko
S
Okuyama
Ryo
R
Abe
Manabu
M
Kurikawa
Nobuya
N
Kawamura
Sayako
S
Yamato
Michiko
M
Osumi
Jun
J
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
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