Synthesis and Anti-HIV-1 Activity of a Novel Series of Aminoimidazole Analogs

被引：9

作者：

Ganguly, Swastika ^{[1
]}

Murugesan, Sankaran ^{[1
]}

Prasanthi, Naru ^{[1
]}

Alpturk, Onur ^{[2
]}

Herman, Brian ^{[2
]}

Sluis-Cremer, Nicolas ^{[2
]}

机构：

[1] Birla Inst Technol, Dept Pharmaceut Sci, Ranchi 835215, Jharkhand, India

[2] Univ Pittsburgh, Dept Med, Div Infect Dis, Pittsburgh, PA 15261 USA

来源：

LETTERS IN DRUG DESIGN & DISCOVERY | 2010年 / 7卷 / 05期

基金：

美国国家卫生研究院;

关键词：

N-aminoimidazole; NNRTI; HIV; Reverse transcriptase; Synthesis; Molecular modeling; HIV-1; REVERSE-TRANSCRIPTASE; IMMUNODEFICIENCY-VIRUS TYPE-1; NONNUCLEOSIDE INHIBITORS; CONFORMATIONAL-CHANGES; ANGSTROM RESOLUTION; DRUG-RESISTANCE; MECHANISMS; REPLICATION; MUTATIONS;

D O I：

10.2174/157018010791163424

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

There is still an urgent need to develop nonnucleoside reverse transcriptase (RT) inhibitors (NNRTI) with a high-genetic barrier to resistance that facilitate patient adherence and allow durable suppression of HIV-1 replication. In this study, we describe the synthesis of a novel series of N-aminoimidazole (NAIM) analogs. Each of the NAIM analogs display potent activity against wild-type recombinant purified HIV-1 RT as well as RTs containing the K103N or Y181C resistance mutations. The analogs, however, do not exhibit significant antiviral activity in cell culture and were, in general, cytotoxic. Nevertheless, these data suggest that the NAIM backbone may provide a suitable scaffold from which inhibitors active against NNRTI-resistant HIV-1 could be developed.

引用

页码：318 / 323

页数：6

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