title: Design and synthesis of N-methylpyrimidone derivatives as HIV-1 integrase inhibitors.
abstract: A series of novel β-diketo derivatives which combined the virtues of dihydroxypyrimidine carboxamide derived from the evolution of DKA and polyhydroxylated aromatics moieties, were designed and synthesized as potential HIV-1 integrase (IN) inhibitors and evaluated their inhibition to the strand transfer process of HIV-1 integrase and anti-HIV-1 activity. The result indicates that 3,4,5-trihydroxylated aromatic derivatives exhibit good inhibition to HIV-1 integrase, but dihydroxylated aromatic derivatives appear little inhibition to HIV-1 integrase. In addition, the preliminary structure-activity relationship (SAR) of these new derivatives was rationalized by docking studies.
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, Beijing, PR China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Wang
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, Beijing, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Rong
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, Beijing, PR China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, Beijing, PR China. Electronic address: huliming@bjut.edu.cn.
authors.forename: Liming
authors.initials: L
authors.lastname: Hu
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, Beijing, PR China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wang
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, Beijing, PR China.
authors.forename: Chengchu
authors.initials: C
authors.lastname: Zeng
mesh_terms: D002460:Cell Line; D015195:Drug Design; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; 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; D062105:Molecular Docking Simulation; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: C576652:3-methyl-4-pyrimidone; D019428:HIV Integrase Inhibitors; D011744:Pyrimidinones; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1
keywords: HIV-1 integrase; Inhibitors; N-Methylpyrimidone; Synthesis