433232-92-9Relevant academic research and scientific papers
Structure-activity relationship of pyrrole based S-nitrosoglutathione reductase inhibitors: Carboxamide modification
Sun, Xicheng,Qiu, Jian,Strong, Sarah A.,Green, Louis S.,Wasley, Jan W.F.,Blonder, Joan P.,Colagiovanni, Dorothy B.,Stout, Adam M.,Mutka, Sarah C.,Richards, Jane P.,Rosenthal, Gary J.
, p. 2338 - 2342 (2012/04/18)
The enzyme S-nitrosoglutathione reductase (GSNOR) is a member of the alcohol dehydrogenase family (ADH) that regulates the levels of S-nitrosothiols (SNOs) through catabolism of S-nitrosoglutathione (GSNO). GSNO and SNOs are implicated in the pathogenesis of many diseases including those in respiratory, gastrointestinal, and cardiovascular systems. The pyrrole based N6022 was recently identified as a potent, selective, reversible, and efficacious GSNOR inhibitor which is currently in clinical development for acute asthma. We describe here the synthesis and structure-activity relationships (SAR) of novel pyrrole based analogs of N6022 focusing on carboxamide modifications on the pendant N-phenyl moiety. We have identified potent and novel GSNOR inhibitors that demonstrate efficacy in an ovalbumin (OVA) induced asthma model in mice.
