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Allosteric inhibitors against HIV-1 reverse transcriptase: design and synthesis of MKC-442 analogues having an
H Tanaka1, R T Walker, A L Hopkins
1School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
Abstract:
Based on X-ray crystallographic analysis of MKC-442/human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) complex, analogues in which the N1-substituent is replaced with omega-functionalized alkyl groups were designed to improve the affinity for the enzyme. Synthesis of these compounds was carried out starting from MKC-442 by a sequence of reactions (N3-protection, removal of N1-ethoxymethyl group, alkylation, and N3-deprotection). The compounds were evaluated for anti-HIV activity. Structure-activity relationships are discussed in terms of the possible interaction with the enzyme.
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