Microwave-accelerated synthesis of P1'-extended HIV-1 protease inhibitors encompassing a tertiary alcohol in the transition-state mimicking scaffold
2006 (English)In: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 49, no 5, 1828-1832 p.Article in journal (Refereed) Published
Two series of P1'-extended HIV-1 protease inhibitors comprising a tertiary alcohol in the transition-state mimic exhibiting Ki values ranging from 2.1 to 93 nM have been synthesized. Microwave-accelerated palladium-catalyzed cross-couplings were utilized to rapidly optimize the P1' side chain. High cellular antiviral potencies were encountered when the P1' benzyl group was elongated with a 3- or 4-pyridyl substituent (EC50 = 0.18-0.22 microM). X-ray crystallographic data were obtained for three inhibitors cocrystallized with the enzyme.
Place, publisher, year, edition, pages
2006. Vol. 49, no 5, 1828-1832 p.
IdentifiersURN: urn:nbn:se:uu:diva-24527DOI: 10.1021/jm051239zISI: 000236005400033PubMedID: 16509598OAI: oai:DiVA.org:uu-24527DiVA: diva2:52301