Synthesis and HIV-1 inhibitory properties of new tetrahydrobenzoquinazolinedione and tetrahydrobenzocycloheptenuracil derivatives and of their thioxoanalogues

Some new tetrahydrobenzoquinazolinediones 2a-4a, tetrahydrobenzocyclohepten uracils 5a, 6a and their thioxo analogues 2b-6b were synthesized within a p roject aimed at obtaining new HIV-1 tricyclic inhibitors whose scaffold inc ludes a pyrimidine and a phenyl ring, which are present in various HIV-1 no n-nucleoside inhibitors. Among the tetrahydrobenzaquinazolinediones 2a-4a, compounds 3a and 4a, in which the tricyclic system is respectively in an an gular or linear arrangement, proved to possess a HIV-1 inhibitory activity which was in the micromolar range, while compound 2a, in which the tricycli c system is in the angular arrangement opposite to that of 3a, was found to be completely inactive. As regards the tetrahydrobenzocycloheptenuracil de rivatives (5a and 6a), only 5a showed an inhibitory activity similar to tha t of 3a and 4a. Furthermore, all thioxo analogues 2b-6b were found to be de void of any activity. (C) 1999 Elsevier Science S.A. All rights reserved.