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

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

43 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

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

SDG 3 Good Health and Well-being

Keywords

C symmetry
HIV-1 protease inhibitor
Sulfoximine
Transition state mimic

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10.1016/j.bmcl.2007.07.095

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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.",

keywords = "C symmetry, HIV-1 protease inhibitor, Sulfoximine, Transition state mimic",

author = "Ding Lu and Robert Vince",

year = "2007",

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doi = "10.1016/j.bmcl.2007.07.095",

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volume = "17",

pages = "5614--5619",

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AU - Lu, Ding

AU - Vince, Robert

PY - 2007/10/15

Y1 - 2007/10/15

N2 - 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.

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.

KW - C symmetry

KW - HIV-1 protease inhibitor

KW - Sulfoximine

KW - Transition state mimic

UR - https://www.scopus.com/pages/publications/34548598162

UR - https://www.scopus.com/pages/publications/34548598162#tab=citedBy

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M3 - Article

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AN - SCOPUS:34548598162

SN - 0960-894X

VL - 17

SP - 5614

EP - 5619

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 20

ER -

Discovery of potent HIV-1 protease inhibitors incorporating sulfoximine functionality

Abstract

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