title: Hydroxyl may not be indispensable for raltegravir: Design, synthesis and SAR Studies of raltegravir derivatives as HIV-1 inhibitors.
abstract: A series of raltegravir derivatives 20-42 were prepared and systematically evaluated for their anti-HIV activity. The bioassay results showed that most of the compounds possess good to excellent anti-HIV activity. Especially, compounds 25 and 35 with subpicomole IC(50) values seemed to be the most potent anti-HIV agents among all of the reported synthesized compounds. These compounds may therefore be considered as new potent anti-HIV agents. The 5-hydroxyl modification of raltegravir derivatives significantly increased the anti-HIV activity, which indicates that the hydroxyl may not be indispensable for raltegravir. The introducing of acyl at 5-position of raltegravir derivatives is favorable for antiviral activity. In addition, a high-throughput cell-based assay method with pseudotyped virus stocks was developed and used to identify HIV inhibitors.
authors.affiliation: State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Nankai University, 94 weijing street, Tianjin 300071, People's Republic of China.
authors.forename: Ziwen
authors.initials: Z
authors.lastname: Wang
authors.forename: Mingxiao
authors.initials: M
authors.lastname: Wang
authors.forename: Xue
authors.initials: X
authors.lastname: Yao
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.forename: Wentao
authors.initials: W
authors.lastname: Qiao
authors.forename: Yunqi
authors.initials: Y
authors.lastname: Geng
authors.forename: Yuxiu
authors.initials: Y
authors.lastname: Liu
authors.forename: Qingmin
authors.initials: Q
authors.lastname: Wang
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001565:Benzoates / Q000138:chemical synthesis* / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D015195:Drug Design; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D015394:Molecular Structure; D010069:Oxadiazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000494:pharmacology*; D000068898:Raltegravir Potassium; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects
chemical_list: C573637:2-(2-(2-(diethylamino)-2-oxoacetamido)propan-2-yl)-4-(4-fluorobenzylcarbamoyl)-1-methyl-6-oxo-1,6-dihydropyrimidin-5-yl benzoate; C573638:4-(4-fluorobenzylcarbamoyl)-1-methyl-2-(2-(5-methyl-1,3,4-oxadiazole-2-carboxamido)propan-2-yl)-6-oxo-1,6-dihydropyrimidin-5-yl benzoate; D019380:Anti-HIV Agents; D001565:Benzoates; D010069:Oxadiazoles; D011744:Pyrimidinones; D011760:Pyrrolidinones; D018894:Reverse Transcriptase Inhibitors; D000068898:Raltegravir Potassium