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- W4231419782 abstract "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 ∼30-fold greater inhibitory effect than MKC-442 to the Tyr181Cys mutant virus as well as to the clinically important Lys103Asn virus. X-ray crystallographic structure determination of complexes with HIV-1 RT confirmed the predicted binding modes. These strategies might be used to improve the resilience of other NNRTI series against common drug-resistance mutations." @default.
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- W4231419782 date "1999-10-09" @default.
- W4231419782 modified "2023-09-24" @default.
- W4231419782 title "Design of MKC-442 (Emivirine) Analogues with Improved Activity Against Drug-Resistant HIV Mutants" @default.
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- W4231419782 doi "https://doi.org/10.1021/jm990192c" @default.
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