title: Synthesis and biological evaluation of novel C5 halogen-functionalized S-DABO as potent HIV-1 non-nucleoside reverse transcriptase inhibitors.
abstract: A series of novel S-DABO analogues (4a1-5a12) have been synthesized by an efficient method and evaluated as inhibitors of human immunodeficiency virus type-1 (HIV-1). The biological testing results clearly indicated that the substitution of halogen at the C5 position of pyrimidine ring could increase the anti-HIV-1 RT activity. The most active compounds showed activity in the low micromole range with IC(50) values (IC(50) 0.18-3.03 microM) comparable to nevirapine (IC(50) 4.12 microM). The docking showed that a new halogen bond was formed between halogen and carbonyl of TYR188 in the HIV-I RT.
authors.affiliation: State key Laboratory of National and Biomimetic Drug, Peking University, Beijing 100191, PR China.
authors.forename: Hua
authors.initials: H
authors.lastname: Qin
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Guo
authors.forename: Ruiping
authors.initials: R
authors.lastname: Wang
authors.forename: Jianfang
authors.initials: J
authors.lastname: Zhang
authors.forename: Liying
authors.initials: L
authors.lastname: Ma
authors.forename: Zhili
authors.initials: Z
authors.lastname: Zhang
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Wang
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Cui
authors.forename: Junyi
authors.initials: J
authors.lastname: Liu
mesh_terms: D015195:Drug Design; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D015497:HIV-1 / Q000187:drug effects*; D006219:Halogens / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D019829:Nevirapine / Q000737:chemistry / Q000494:pharmacology; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013455:Sulfur / Q000737:chemistry
chemical_list: C092123:DABO 546; D006219:Halogens; D011744:Pyrimidinones; D018894:Reverse Transcriptase Inhibitors; D013455:Sulfur; D019829:Nevirapine; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase