Epsilon substituted lysinol derivatives as HIV-1 protease inhibitors

…, C Burlein, S Touch, DJ DiStefano, RI Sanchez…

Index: Jones, Kristen L.G.; Holloway, M. Katharine; Su, Hua-Poo; Carroll, Steven S.; Burlein, Christine; Touch, Sinoeun; DiStefano, Daniel J.; Sanchez, Rosa I.; Williams, Theresa M.; Vacca, Joseph P.; Coburn, Craig A. Bioorganic and Medicinal Chemistry Letters, 2010 , vol. 20, # 14 p. 4065 - 4068

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Citation Number: 5

Abstract

A series of HIV-1 protease inhibitors containing an epsilon substituted lysinol backbone was synthesized. Two novel synthetic routes using N-boc-l-glutamic acid alpha-benzyl ester and 2, 6-diaminopimelic acid were developed. Incorporation of this epsilon substituent enabled access to the S2 pocket of the enzyme, affording high potency inhibitors. Modeling studies and synthetic efforts suggest the potency increase is due to both conformational bias and ...