ALLOSTERIC INHIBITORS AGAINST HIV-1 REVERSE-TRANSCRIPTASE - DESIGN AND SYNTHESIS OF MKC-442 ANALOGS HAVING AN OMEGA-FUNCTIONALIZED ACYCLIC STRUCTURE

Based on X-ray crystallographic analysis of MKC-442/human immunodefici ency virus type 1 reverse transcriptase (HIV-1 RT) complex, analogues in which the N1-substituent is replaced with omega-functionalized alky l groups were designed to improve the affinity for the enzyme. Synthes is of these compounds was carried out starting from MKC-442 by a seque nce of reactions (N3-protection, removal of N1-ethoxymethyl group, alk ylation, and N3-deprotection). The compounds were evaluated for anti-H IV activity. Structure-activity relationships are discussed in terms o f the possible interaction with the enzyme.