Microwave-accelerated synthesis of P1'-extended HIV-1 protease inhibitors encompassing a tertiary alcohol in the transition-state mimicking scaffold

Journal of Medicinal Chemistry
Jenny K EkegrenAnders Hallberg

Abstract

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.

References

Aug 1, 1991·Journal of Medicinal Chemistry·M W MoonV H Sethy
Oct 14, 1994·Journal of Medicinal Chemistry·B D DorseyJ C Quintero
Apr 26, 1994·Proceedings of the National Academy of Sciences of the United States of America·J P VaccaE Roth
Jun 6, 2000·Advanced Drug Delivery Reviews· T Borchardt RG M Pauletti
Jun 22, 2000·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·E P AcostaC V Fletcher
Apr 13, 2001·Drug Discovery Today·M Larhed, A Hallberg
Sep 18, 2002·Accounts of Chemical Research·Mats LarhedAnders Hallberg
Jul 2, 2003·Nature Medicine·Roger J Pomerantz, David L Horn
Jul 15, 2003·Journal of Combinatorial Chemistry·Daniel NötebergMats Larhed
Aug 22, 2003·Organic & Biomolecular Chemistry·Ashraf Brik, Chi-Huey Wong
May 12, 2004·Current Topics in Medicinal Chemistry·Fátima Rodríguez-Barrios, Federico Gago
May 25, 2004·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Diane V Havlir, Steven D O'Marro
Jun 15, 2004·Current Topics in Medicinal Chemistry·John T Randolph, David A DeGoey
Mar 4, 2005·Journal of Medicinal Chemistry·Erik De Clercq
Dec 13, 2005·Journal of Medicinal Chemistry·Jenny K EkegrenAnders Hallberg
Dec 24, 2005·Nature Reviews. Drug Discovery·C Oliver Kappe, Doris Dallinger

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Citations

Jan 23, 2016·Journal of Medicinal Chemistry·Arun K GhoshGary Prato
Dec 8, 2014·European Journal of Medicinal Chemistry·Hitesh V MotwaniMats Larhed
Apr 18, 2009·Current Opinion in HIV and AIDS·Sergei V Gulnik, Michael Eissenstat
Nov 19, 2013·Pharmaceutical Patent Analyst·Mitesh PatelAshim K Mitra
Sep 25, 2014·Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry·Thomas C SchmidtBernd Engels
Oct 29, 2013·Journal of Medicinal Chemistry·Advait JoshiMats Larhed

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