Synthesis and biological evaluation of imidazole thioacetanilides as novel non-nucleoside HIV-1 reverse transcriptase inhibitors.
A series of 2-(1-aryl-1H-imidazol-2-ylthio)acetamide [imidazole thioacetanilide (ITA)] derivatives were synthesized and evaluated as potent inhibitors of human immunodeficiency virus type-1 (HIV-1). Among them, the most potent HIV-1 inhibitors were 4a5 (EC(50)=0.18microM), and 4a2 (EC(50)=0.20microM), which were more effective than the lead compound L1 (EC(50)=2.053microM) and the reference drugs nevirapine and delavirdine. The preliminary structure-activity relationship (SAR) of the newly synthesized congeners is discussed.
Zhan
Peng
P
Institute of Medicinal Chemistry, Shandong University, Jinan, PR China.
Liu
Xinyong
X
Zhu
Junjie
J
Fang
Zengjun
Z
Li
Zhenyu
Z
Pannecouque
Christophe
C
Clercq
Erik De
ED
D000083:Acetanilides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D003198:Computer Simulation; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000083:Acetanilides; D019380:Anti-HIV Agents; D007093:Imidazoles; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; C039632:thioacetanilide