MedChemComm p. 444 - 454 (2015)
Update date:2022-08-05
Topics:
Gao, Jiadi
Fang, Cheng
Xiao, Zhiyan
Huang, Li
Chen, Chin-Ho
Wang, Li-Ting
Lee, Kuo-Hsiung
Based on a 3D-QSAR pharmacophore derived from a diverse set of known cyclin-dependent kinase 9 (CDK9) inhibitors and a composite pharmacophore extracted from the complex structure of flavopiridol (FVP)-CDK9, thirty novel 5-fluoro-N2,N4-diphenylpyrimidine-2,4-diamine derivatives were designed and synthesized. Initial tests against four tumor cell lines with the sulforhodamine B (SRB) assay identified a series of potent compounds with GI50 values at a lower micromolar or submicromolar level. Most of the highly cytotoxic compounds exhibited potent inhibitory activities against both CDK2/cyclin E1 and CDK9/cyclin T1. Notably, inhibitions against the two enzymes were generally correlated well with the cytotoxicity of these compounds. Appreciable inhibition was also observed for selected compounds in the anti-HIV-1 assay. Docking studies on compounds 6d and 9g provided conducive clues to further structural optimization. This journal is
View MoreContact:+852-8198 2399
Address:9E, Leapont Industrial Building, 18-28 Wo Liu Hang Road, Shatin, New Territories, Hong Kong
Hangzhou Ocean Chemical Co., Ltd.
website:http://www.hzoceanchem.com
Contact:+86-571-88025872, 28272092, 28272096
Address:Room 623 ,Building No 1 , COFCO Radius Commercial Center Xiwen Road, Xiacheng District, Hangzhou, Zhejiang Province, China
Heliosense Biotechnologies, Inc.
Contact:+86-592-5667290
Address:Xiamen Torch Hi-tech Zone Venture Weiye Building S506
Tianjin Ingenochem Technology Co.,Ltd
Contact:+86-22-23677060
Address:Hitech Green Industry Park K2-9-602, Nankai district
Contact:+86-571-28186845
Address:Room 1224,Eastcom Mansion,398 Wensan Road,Hangzhou,310013 China
Doi:10.1016/j.jfluchem.2007.05.004
(2007)Doi:10.1021/ol801272e
(2008)Doi:10.1002/ejoc.201901118
(2019)Doi:10.1248/cpb.34.931
(1986)Doi:10.1055/s-1990-27021
(1990)Doi:10.1021/jo801116n
(2008)