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

ABSTRACT: 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.

SUBMITTER: Ganguly S

PROVIDER: S-EPMC2882308 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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

Ganguly Swastika S Murugesan Sankaran S Prasanthi Naru N Alptürk Onur O Herman Brian B Sluis-Cremer Nicolas N

Letters in drug design & discovery 20100601 5

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, ...[more]

PMID: 20535242

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