Document Detail


Discovery of potent HIV-1 protease inhibitors incorporating sulfoximine functionality.
MedLine Citation:
PMID:  17822899     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Based on the unique property of sulfoximine and the homodimeric C(2) 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 (IC(50)) against HIV-1 protease and an anti-HIV-1 activity of 408 nM (IC(50)). A possible mode of action is proposed.
Authors:
Ding Lu; Robert Vince
Related Documents :
19956769 - Asymmetric deactivation of hiv-1 gp41 following fusion inhibitor binding.
15225729 - Synthesis and antiviral activity of p1' arylsulfonamide azacyclic urea hiv protease inh...
17236209 - Disruption of the hiv-1 protease dimer with interface peptides: structural studies usin...
9195919 - A metal-induced conformational change and activation of hiv-1 integrase.
10775609 - Alteration of substrate and inhibitor specificity of feline immunodeficiency virus prot...
15811379 - Crystal structure of cockroach allergen bla g 2, an unusual zinc binding aspartic prote...
15894609 - Physics-based protein-structure prediction using a hierarchical protocol based on the u...
10320809 - Characterization of the transacylase activity of rat liver 60-kda lysophospholipase-tra...
16190669 - Conformational study of globulin from common buckwheat (fagopyrum esculentum moench) by...
Publication Detail:
Type:  Journal Article     Date:  2007-08-23
Journal Detail:
Title:  Bioorganic & medicinal chemistry letters     Volume:  17     ISSN:  0960-894X     ISO Abbreviation:  Bioorg. Med. Chem. Lett.     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-09-18     Completed Date:  2007-12-12     Revised Date:  2008-06-09    
Medline Journal Info:
Nlm Unique ID:  9107377     Medline TA:  Bioorg Med Chem Lett     Country:  England    
Other Details:
Languages:  eng     Pagination:  5614-9     Citation Subset:  IM    
Affiliation:
Department of Medicinal Chemistry, College of Pharmacy, 308 Harvard Street SE, University of Minnesota, Minneapolis, MN 55455, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Drug Design*
HIV Protease Inhibitors / chemical synthesis,  chemistry*,  pharmacology*
Models, Molecular
Molecular Structure
Oximes / chemical synthesis,  chemistry*,  pharmacology*
Sulfur / chemistry*
Chemical
Reg. No./Substance:
0/HIV Protease Inhibitors; 0/Oximes; 7704-34-9/Sulfur
Comments/Corrections
Erratum In:
Bioorg Med Chem Lett. 2008 Mar 15;18(6):2228

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Dihydroxypyridopyrazine-1,6-dione HIV-1 integrase inhibitors.
Next Document:  Pyrazole-based cathepsin S inhibitors with improved cellular potency.