Abstract
Two cyclic, C2-symmetric HIV-1 protease inhibitors, one sulfamide and one urea derivative, both comprising phenyl ether groups in the P1/P1' positions, were cocrystallized with HIV-1 protease, and the crystal structures were determined to 2.0 A resolution. The structure of the urea 2 showed a conformation similar to that reported for the related urea 3 by Lam et al., while the sulfamide 1 adopted an unanticipated conformation in which the P1' and P2' side chains were transposed.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Azepines / chemistry*
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Azepines / metabolism
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Azepines / pharmacology
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Binding Sites
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Crystallization
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Crystallography, X-Ray
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HIV Protease / chemistry*
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HIV Protease / metabolism
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HIV Protease Inhibitors / chemistry*
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HIV Protease Inhibitors / metabolism
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HIV Protease Inhibitors / pharmacology
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HIV-1 / enzymology*
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Models, Molecular
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Molecular Conformation
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Molecular Structure
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Protein Binding
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Sulfonamides / chemistry*
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Sulfonamides / metabolism
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Sulfonamides / pharmacology
Substances
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1,3-dibenzyl-5,6--dihydroxy-4,7-di-(phenoxymethyl)-1,3-azepin-2-one
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1,3-dibenzyl-5,6-dihydroxy-4,7-di-(phenoxymethyl)-2-thia-1,3-azepine S,S-dioxide
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Azepines
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HIV Protease Inhibitors
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Sulfonamides
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HIV Protease