Title of article
Design, synthesis and characterization of a novel class of coumarin-based inhibitors of inducible nitric oxide synthase Original Research Article
Author/Authors
Sharon A. Jackson، نويسنده , , Sukhveen Sahni، نويسنده , , Lan Lee، نويسنده , , Yongyi Luo، نويسنده , , Thaddeus R. Nieduzak، نويسنده , , Guyan Liang، نويسنده , , Yulin Chiang، نويسنده , , Nicola Collar، نويسنده , , David Fink، نويسنده , , Wei He، نويسنده , , Abdelazize Laoui، نويسنده , , Jean Merrill، نويسنده , , Ray Boffey، نويسنده , , Peter Crackett، نويسنده , , Bryan Rees، نويسنده , , Melanie Wong، نويسنده , , Jean-Pierre Guilloteau، نويسنده , , Magali Mathieu، نويسنده , , Sam S. Rebello، نويسنده ,
Issue Information
روزنامه با شماره پیاپی سال 2005
Pages
17
From page
2723
To page
2739
Abstract
Inducible nitric oxide synthase (iNOS) has been implicated in various central and peripheral pathophysiological diseases. Our high throughput screening initially identified a weak inhibitor of iNOS, thiocoumarin 13. From this lead, a number of potent derivatives were prepared that demonstrate favorable potency, selectivity and kinetics. Compound 30 has an IC50 of 60 nM for mouse iNOS and 185-fold and 9-fold selectivity for bovine eNOS and rat nNOS, respectively. In cellular assays for iNOS, this compound has micromolar potency. Furthermore, two compounds (16 and 30) demonstrate a reasonable pharmacokinetic profile in rodents. The synthesis, SAR, and biological activity of this novel class of compounds is described.
Keywords
iNOS inhibition , Coumarin
Journal title
Bioorganic and Medicinal Chemistry
Serial Year
2005
Journal title
Bioorganic and Medicinal Chemistry
Record number
1304627
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