title: Rational design of 2-pyrrolinones as inhibitors of HIV-1 integrase.
abstract: HIV-1 integrase is an essential enzyme for viral replication and a validated target for the development of drugs against AIDS. With an aim to discover new potent inhibitors of HIV-1 integrase, we developed a pharmacophore model based on reported inhibitors embodying structural diversity. Eight compounds of 2-pyrrolinones fitting all the features of the pharmacophore query were found through the screening of an in-house database. These candidates were successfully synthesized, and three of them showed strand transfer inhibitory activity, in which, one compound showed antiviral activity. Further mapping analysis and docking studies affirmed these results.
authors: Department of Medicinal Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, PR China.
authors: Kaiqing
authors: K
authors: Ma
authors: Penghui
authors: P
authors: Wang
authors: Wei
authors: W
authors: Fu
authors: Xiaolong
authors: X
authors: Wan
authors: Lu
authors: L
authors: Zhou
authors: Yong
authors: Y
authors: Chu
authors: Deyong
authors: D
authors: Ye
mesh_terms: D015195:Drug Design; D015658:HIV Infections / Q000188:drug therapy; D019427:HIV Integrase / Q000378:metabolism*; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D008958:Models, Molecular; D011760:Pyrrolidinones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D019428:HIV Integrase Inhibitors; D011760:Pyrrolidinones; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1