Dicaffeoyl- or digalloyl pyrrolidine and furan derivatives as HIV integrase inhibitors

Human immunodeficiency virus (HIV) integrase (IN) catalyzes the integration of HIV DNA copy into the host cell DNA. Such integration is essential for the production of progeny viruses, and therefore therapeutic agents that ca n inhibit this process should be effective anti-HIV agents. We have previou sly reported the inhibitory activity of dicaffeoylglucosides against HIV IN . In the present study, we have synthesized and tested dicaffeoyl or digall oyl compounds joined through a five-membered heterocyclic ring as HIV IN in hibitors to explore the SARs of this family of compounds. The starting hete rocyclic diols were prepared from L-tartaric acid, diethyl L-tartarate or D -(+)-ribonic gamma -lactone. We found that the HIV IN inhibitory activities of dicaffeoyl derivatives were comparable to that of L-chicoric acid (IC50 = 24.9 muM). On the other hand, digalloyl derivatives were more potent tha n L-chicoric acid with IC50 Values of 4.7-15.6 muM. (C) 2001 Elsevier Scien ce Ltd. All rights reserved.