Epsilon substituted lysinol derivatives as HIV-1 protease inhibitors

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• 作者：Kristen L.G. Jones ; M. Katharine Holloway ; Hua-Poo Su ; Steven S. Carroll ; Christine Burlein ; Sinoeun Touch ; Daniel J. DiStefano ; Rosa I. Sanchez ; Theresa M. Williams ; Joseph P. Vacca ; Craig A. Coburn
• 关键词：HIV-1 protease inhibitor ; Lysinol sulfonamide
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2010
• 出版时间：15 July 2010
• 年：2010
• 卷：20
• 期：14
• 页码：4065-4068
• 全文大小：714 K

文摘

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 van der Waals interactions with the S2 pocket.