Cyclic sulfone-3-carboxamides as novel P2-ligands for Ro 31-8959 based HIV-1 protease inhibitors
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چکیده
منابع مشابه
Design and synthesis of HIV-1 protease inhibitors incorporating oxazolidinones as P2/P2' ligands in pseudosymmetric dipeptide isosteres.
A series of novel HIV-1 protease inhibitors based on two pseudosymmetric dipeptide isosteres have been synthesized and evaluated. The inhibitors were designed by incorporating N-phenyloxazolidinone-5-carboxamides into the hydroxyethylene and (hydroxyethyl)hydrazine dipeptide isosteres as P2 and P2' ligands. Compounds with (S)-phenyloxazolidinones attached at a position proximal to the central h...
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A combination of structure-activity studies, kinetic analysis, X-ray crystallographic analysis, and modeling were employed in the design of a novel series of HIV-1 protease (HIV PR) inhibitors. The crystal structure of a complex of HIV PR with SRSS-2,5-bis[N-(tert-butyloxycarbonyl)amino]-3,4-dihydroxy-1, 6-diphenylhexane (1) delineated a crucial water-mediated hydrogen bond between the tert-but...
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Treatment of human immunodeficiency virus type 1 (HIV-1) infection with regimens that include protease inhibitors (PIs) has contributed to marked improvements in HIV-related disease progression and mortality. Five PIs are approved by the US Food and Drug Administration and have potent activity in vitro. PIs with 2 nucleoside analogue reverse transcriptase inhibitors have demonstrated prolonged ...
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In AIDS therapy, attempts have been made to inhibit the virus-encoded enzymes, e.g. HIV-1 protease, using active site-directed inhibitors. This approach is questionable, however, due to virus mutations and the high toxicity of the drugs. An alternative method to inhibit the dimeric HIV protease is the targeting of the interface region of the protease subunits in order to prevent subunit dimeriz...
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The design, development and clinical success of HIV protease inhibitors represent one of the most remarkable achievements of molecular medicine. This review describes all nine currently available FDA-approved protease inhibitors, discusses their pharmacokinetic properties, off-target activities, side-effects, and resistance profiles. The compounds in the various stages of clinical development a...
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ژورنال
عنوان ژورنال: Bioorganic & Medicinal Chemistry Letters
سال: 1995
ISSN: 0960-894X
DOI: 10.1016/0960-894x(94)00463-p