164083-65-2Relevant articles and documents
Structure-based design, synthesis, and biological evaluation of indomethacin derivatives as cyclooxygenase-2 inhibiting nitric oxide donors
Wey, Shiow-Jyi,Augustyniak, Michael E.,Cochran, Edward D.,Ellis, James L.,Fang, Xinqin,Garvey, David S.,Janero, David R.,Letts, L. Gordon,Martino, Allison M.,Melim, Terry L.,Murty, Madhavi G.,Richardson, Steward K.,Schroeder, Joseph D.,Selig, William M.,Trocha, A. Mark,Wexler, Roseanne S.,Young, Delano V.,Zemtseva, Irina S.,Zifcak, Brian M.
, p. 6367 - 6382 (2008/03/27)
Indomethacin, a nonselective cyclooxygenase (COX) inhibitor, was modified in three distinct regions in an attempt both to increase cyclooxygenase-2 (COX-2) selectivity and to enhance drug safety by covalent attachment of an organic nitrate moiety as a nitric oxide donor. A human whole-blood COX assay shows the modifications on the 3-acetic acid part of the indomethacin yielding an amide-nitrate derivative 32 and a sulfonamide-nitrate derivative 61 conferred COX-2 selectivity. Along with their respective des-nitrate analogs, for example, 31 and 62, the nitrates 32 and 61 were effective antiinflammatory agents in the rat air-pouch model. After oral dosing, though, only 32 increased nitrate and nitrite levels in rat plasma, indicating that its nitrate tether served as a nitric oxide donor in vivo. In a rat gastric injury model, examples 31 and 32 both show a 98% reduction in gastric lesion score compared to that of indomethacin. In addition, the nitrated derivative 32 inducing 85% fewer gastric lesions when coadministered with aspirin as compared to the combination of aspirin and valdecoxib.
1H-INDOLE-3-ACETAMIDE SPLA2 INHIBITORS
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, (2008/06/13)
A class of novel 1-indole-3-acetamides represented by the formula; is disclosed together with the use of such indole compounds for inhibiting sPLA2 mediated release of fatty acids.
