Discovery of potent HIV-1 protease inhibitors incorporating sulfoximine functionality

Ding Lu; Robert Vince

doi:10.1016/j.bmcl.2007.07.095

Discovery of potent HIV-1 protease inhibitors incorporating sulfoximine functionality

Ding Lu, Robert Vince

Center for Drug Design

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

38 Scopus citations

Abstract

Based on the unique property of sulfoximine and the homodimeric C₂ structural symmetry of HIV-1 protease, a novel class of sulfoximine-based pseudosymmetric HIV-1 protease inhibitors was designed and synthesized. The sulfoximine moiety was demonstrated to be important for HIV-1 protease inhibitor potency. The most active stereoisomer (2S,2′S) displays a potency of 2.5 nM (IC₅₀) against HIV-1 protease and an anti-HIV-1 activity of 408 nM (IC₅₀). A possible mode of action is proposed.

Original language	English (US)
Pages (from-to)	5614-5619
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	17
Issue number	20
DOIs	https://doi.org/10.1016/j.bmcl.2007.07.095
State	Published - Oct 15 2007

Keywords

C symmetry
HIV-1 protease inhibitor
Sulfoximine
Transition state mimic

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "Discovery of potent HIV-1 protease inhibitors incorporating sulfoximine functionality",

abstract = "Based on the unique property of sulfoximine and the homodimeric C2 structural symmetry of HIV-1 protease, a novel class of sulfoximine-based pseudosymmetric HIV-1 protease inhibitors was designed and synthesized. The sulfoximine moiety was demonstrated to be important for HIV-1 protease inhibitor potency. The most active stereoisomer (2S,2′S) displays a potency of 2.5 nM (IC50) against HIV-1 protease and an anti-HIV-1 activity of 408 nM (IC50). A possible mode of action is proposed.",

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AB - Based on the unique property of sulfoximine and the homodimeric C2 structural symmetry of HIV-1 protease, a novel class of sulfoximine-based pseudosymmetric HIV-1 protease inhibitors was designed and synthesized. The sulfoximine moiety was demonstrated to be important for HIV-1 protease inhibitor potency. The most active stereoisomer (2S,2′S) displays a potency of 2.5 nM (IC50) against HIV-1 protease and an anti-HIV-1 activity of 408 nM (IC50). A possible mode of action is proposed.

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KW - Sulfoximine

KW - Transition state mimic

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Discovery of potent HIV-1 protease inhibitors incorporating sulfoximine functionality

Abstract

Keywords

UN SDGs

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