Design of MKC-442 (emivirine) analogues with improved activity against drug-resistant HIV mutants.

Journal article

Two analogues of the nonnucleoside inhibitor of HIV-1 RT, MKC-442 (emivirine), containing different C6 substituents have been designed to be less susceptible to the commonly found drug-resistance mutation of Tyr181Cys. Compound TNK-6123 had a C6 thiocyclohexyl group designed to have more flexibility in adapting to the mutated drug-binding site. GCA-186 had additional 3',5'-dimethyl substituents aimed at forming close contacts with the conserved residue Trp229. Both compounds showed approximat...

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Authors: Hopkins, A; Ren, J; Tanaka, H; Baba, M; Okamato, M

• Publication status: Published
• Journal: Journal of medicinal chemistry
• Volume: 42
• Issue: 22
• Pages: 4500-4505
• Publication date: 1999-11-01
• DOI: 10.1021/jm990192c
• EISSN: 1520-4804
• ISSN: 0022-2623
• Language: English
• Keywords: Cell Line; Uracil; Anti-HIV Agents; Drug Resistance, Microbial; Mutation; Drug Design; Reverse Transcriptase Inhibitors; Molecular Conformation; Models, Molecular; Crystallography, X-Ray; Animals; HIV-1