Synthesis and biological evaluation of novel C5 halogen-functionalized S-DABO as potent HIV-1 non-nucleoside reverse transcriptase inhibitors.
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.
Qin
Hua
H
State key Laboratory of National and Biomimetic Drug, Peking University, Beijing 100191, PR China.
Liu
Chang
C
Guo
Ying
Y
Wang
Ruiping
R
Zhang
Jianfang
J
Ma
Liying
L
Zhang
Zhili
Z
Wang
Xiaowei
X
Cui
Yuxin
Y
Liu
Junyi
J
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
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