Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10594938 | Bioorganic & Medicinal Chemistry Letters | 2010 | 4 Pages |
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 van der Waals interactions with the S2 pocket.
Keywords
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
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,