Design and synthesis of sulfoximine based inhibitors for HIV-1 protease

Abbas Raza; Yuk Yin Sham; Robert Vince

doi:10.1016/j.bmcl.2008.09.044

Design and synthesis of sulfoximine based inhibitors for HIV-1 protease

Abbas Raza, Yuk Yin Sham, Robert Vince

Center for Drug Design

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

Abstract

A new class of potent sulfoximine inhibitors for HIV-1 protease has been designed and synthesized. Substitution of the sulfoximine moiety into different parent compounds yields different inhibition effects. While our previously studied sulfoximine-based inhibitors display potency of 2.5 nM (IC₅₀) against HIV-1 protease, introduction of the sulfoximine moiety into the asymmetric Indinavir yielded only micromolar inhibition. Docking studies showed structural variations in their modes of binding which explains this unexpected observation. The implication of these observations in the development of other sulfoximine inhibitors is discussed.

Original language	English (US)
Pages (from-to)	5406-5410
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	18
Issue number	20
DOIs	https://doi.org/10.1016/j.bmcl.2008.09.044
State	Published - Oct 15 2008

Bibliographical note

Funding Information:
This research work was supported by the Center for Drug Design (CDD) at the University of Minnesota. We thank Ms. Christine Dreis, CDD for HIV protease assay. We thank the Minnesota Supercomputing Institute at the University of Minnesota for computational resources.

Keywords

Crystallographic water
Docking studies
HAART
HIV protease
Indinavir
Sulfoximine
TSM binding
Transition state mimic

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title = "Design and synthesis of sulfoximine based inhibitors for HIV-1 protease",

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AU - Vince, Robert

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Design and synthesis of sulfoximine based inhibitors for HIV-1 protease

Abstract

Bibliographical note

Keywords

UN SDGs

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