High-Speed Synthesis of Potent C2-Symmetric HIV-1 Protease Inhibitors by in Situ Aminocarbonylations
2005 (English)In: Journal of combinatorial chemistry, ISSN 1520-4766, E-ISSN 1520-4774, Vol. 7, no 4, 611-617 p.Article in journal (Refereed) Published
Two novel series of C2-symmetric HIV-1 protease inhibitors were synthesized by microwave-promoted, palladium-catalyzed aminocarbonylations of the o-iodo- and m-bromobenzyloxy P1/P1' substituted core structures. Molybdenum hexacarbonyl was used as a convenient solid source of carbon monoxide in these transformations. After the initial high-speed library generation, biological testing identified highly active HIV-1 protease inhibitors. Selected ortho- and meta-decorated inhibitors were subsequently resynthesized on a larger scale and retested for their affinity toward HIV-1 protease, showing micromolar to low nanomolar inhibition. The discovery of highly active inhibitors containing large phenyl amide ortho substituents in the P1/P1' positions indicates that larger groups than previously believed are tolerated in this part of the S1/S1' pocket.
Place, publisher, year, edition, pages
2005. Vol. 7, no 4, 611-617 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-93075PubMedID: 16004505OAI: oai:DiVA.org:uu-93075DiVA: diva2:166442