Molecular association for the design of anti-HIV-1 agents. Conformational study of {3 '-azido-3 '-deoxythymidine} - {4,5,6,7-tetrahydro-5-methylimidazo-[4,5,1-jk][1,4]benzodiazepin-2(1H)-one} derivatives

The association of 3'-azido-3'-deoxythymidine (AZT) 1 and 4,5,6,7-tetrahydr o-9-chloro-5-methylimidazo-[4,5,1-jk][1,4]benzodiazepin-2(1H)-one (TIBO) 2 by use of malonate-, adipate- and propionate-bridges can provide a new kind of cytotoxic agent to fight HIV-1. In this work we show a semiempirical (A M1) conformational study of these AZT-TIBO derivatives. Only small energy a nd electronic differences were found among the conformers for both AZT and TIBO moieties, and all the examined molecules have similar behavior. While the TIBO-fragment does not show a significant conformational change, confor mers of AZT-fragment were slightly affected by the molecular association. ( C) 2000 Elsevier Science B.V. All rights reserved.