Bioorganic and Medicinal Chemistry Letters p. 3721 - 3725 (2018)
Update date:2022-08-05
Topics:
Hu, Carol H.
Wang, Tammy C.
Qiao, Jennifer X.
Haque, Lauren
Chen, Alice Y.A.
Taylor, David S.
Ying, Xiaohong
Onorato, Joelle M.
Galella, Michael
Shen, Hong
Huang, Christine S.
Toussaint, Nathalie
Li, Yi-Xin
Abell, Lynn
Adam, Leonard P.
Gordon, David
Wexler, Ruth R.
Finlay, Heather J.
Endothelial lipase (EL) inhibitors have been shown to elevate HDL-C levels in pre-clinical murine models and have potential benefit in prevention and treatment of cardiovascular diseases. Modification of the 1-ethyl-3-hydroxy-1,5-dihydro-2H-pyrrol-2-one (DHP) lead, 1, led to the discovery of a series of potent tetrahydropyrimidinedione (THP) EL inhibitors. Synthesis and SAR studies including modification of the amide group, together with changes on the pyrimidinone core led to a series of arylcycloalkyl, indanyl, and tetralinyl substituted 5-amino or 5-hydroxypyrimidinedione-4-carboxamides. Several compounds were advanced to PK evaluation. Among them, compound 4a was one of the most potent with measurable ELHDL hSerum potency and compound 3g demonstrated the best overall pharmacokinetic parameters.
View MoreContact:+86-574-89075960
Address:#100 Xiang Yun Road, New High tech area, Ningbo, China
Shenzhen Tianyuan Pharmaceutical Technology Co., Ltd
website:http://www.tianpharm.com
Contact:86-755-23284190
Address:B302,2 unit, Jin Lian Building, No. 134 Qianjin 2 Road, Taoyuan village, Xixiang Street, Baoan,Shenzhen,China
A.M FOOD CHEMICAL CO., LIMITED
Contact:86-531-87100375
Address:20Floor,Bblock,1Building,pharma-valley,Jinan,China
Wuxi D-Stone International Co., Ltd.
Contact:+86-510-82740567
Address:21F Hengtong Int'l Centre, 215Zhongshan Road, Wuxi, Jiangsu,China
Hangzhou GreenCo Science & Technology Co., Ltd.
Contact:86-571-88257303
Address:1713 Room,Jingui Building,Gudun Road,Xihu District,Hangzhou,China
Doi:10.1021/jo01299a055
(1980)Doi:10.1016/S0040-4039(01)86475-3
(1979)Doi:10.1055/s-0037-1611737
(2019)Doi:10.1039/c39800000061
(1980)Doi:10.1016/S0040-4039(01)81862-1
(1981)Doi:10.1021/ja00370a040
(1982)