Bioorganic and Medicinal Chemistry Letters p. 526 - 531 (2014)
Update date:2022-08-03
Topics:
Sun, Shaoyi
Zhang, Zaihui
Raina, Vandna
Pokrovskaia, Natalia
Hou, Duanjie
Namdari, Rostam
Khakh, Kuldip
Ratkay, Leslie G.
McLaren, David G.
Mork, Monica
Fu, Jianmin
Ferreira, Suzie
Hubbard, Brian
Winther, Michael D.
Dales, Natalie
We discovered a series of novel and potent thiazolylpyridinone-based SCD1 inhibitors based on a 2-aminothiazole HTS hit by replacing the amide bond with a pyridinone moiety. Compound 19 demonstrated good potency against SCD1 in vitro and in vivo. The mouse liver microsomal SCD1 in vitro potency for 19 was improved by more than 240-fold compared to the original HTS hit. Furthermore, 19 demonstrated a dose-dependent reduction of plasma desaturation index with an ED50 of 6.3 mg/kg. Compound 19 demonstrated high liver to plasma and liver to eyelid exposures, indicating preferential liver distribution. The preliminary toxicology study with compound 19 did not demonstrate adverse effects related to SCD1 inhibition, suggesting a wide safety margin with respect to other known SCD1 inhibitors with wider distribution profiles.
View MoreCGeneTech (Suzhou, China) Co., Ltd.
Contact:+86-512-62956962
Address:Room 101,Bld C11,218 Xinghu Rd.,Suzhou industrial Park
Changzhou Jiana Chemical Co.,Ltd
website:http://www.jianachem.com
Contact:86-0519-88731808
Address:Zhenglu Town Wujin City, Jiangsu Province
Contact:+86-571-28186845
Address:Room 1224,Eastcom Mansion,398 Wensan Road,Hangzhou,310013 China
Contact:+31-24-3886056
Address:Binderskampweg 29 Unit 36
Beijing Greenchem Technology Co.,Ltd. ( Panjin Greenchem Technology Co.Ltd .)
website:http://www.bjgreenchem.com/
Contact:+86-427-6515887
Address:301,302, 3rd Floor, Building C-7, Dongsheng Science Park, Northern Territory, Zhongguancun, No. 66, Xixiaokou Road, Haidian District, Beijing
Doi:10.1016/0040-4020(96)00200-1
(1996)Doi:10.1016/0008-6215(95)00379-7
(1996)Doi:10.1080/07328309608005696
(1996)Doi:10.1080/00397911.2011.558665
(2012)Doi:10.1016/0022-328X(95)05933-G
(1996)Doi:10.1016/S0040-4020(96)00931-3
(1996)