- Pyrrole inhibitors of S-nitrosoglutathione reductase as therapeutic agents
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The present invention is directed to inhibitors of S-nitrosoglutathione reductase (GSNOR), pharmaceutical compositions comprising such GSNOR inhibitors, and methods of making and using the same.
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Page/Page column 235
(2015/11/16)
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- Discovery of potent and novel S-nitrosoglutathione reductase inhibitors devoid of cytochrome P450 activities
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The pyrrole based N6022 was recently identified as a potent, selective, reversible, and efficacious S-nitrosoglutathione reductase (GSNOR) inhibitor and is currently undergoing clinical development for the treatment of acute asthma. GSNOR is a member of the alcohol dehydrogenase family (ADH) and regulates the levels of S-nitrosothiols (SNOs) through catabolism of S-nitrosoglutathione (GSNO). Reduced levels of GSNO, as well as other nitrosothiols (SNOs), have been implicated in the pathogenesis of many diseases including those of the respiratory, cardiovascular, and gastrointestinal systems. Preservation of endogenous SNOs through GSNOR inhibition presents a novel therapeutic approach with broad applicability. We describe here the synthesis and structure-activity relationships (SAR) of novel pyrrole based analogues of N6022 focusing on removal of cytochrome P450 inhibition activities. We identified potent and novel GSNOR inhibitors having reduced CYP inhibition activities and demonstrated efficacy in a mouse ovalbumin (OVA) model of asthma.
- Sun, Xicheng,Qiu, Jian,Strong, Sarah A.,Green, Louis S.,Wasley, Jan W.F.,Blonder, Joan P.,Colagiovanni, Dorothy B.,Mutka, Sarah C.,Stout, Adam M.,Richards, Jane P.,Rosenthal, Gary J.
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supporting information; experimental part
p. 5849 - 5853
(2011/10/19)
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- OXAZOLIDINONES CONTAINING OXINDOLES AS ANTIBACTERIAL AGENTS
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The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof wherein X is C1-4alkyl; and Y is H or F. The compounds of the present invention are useful as antibacterial agents.
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Page/Page column 18
(2008/06/13)
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- INDAZOLE OXAZOLIDINONES AS ANTIBACTERIAL AGENTS
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The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof wherein: W is C(=O)NHR1, C(=S)NHR1, or CH2het; Y is H, or CF; R1 is H, C16alkyl, or OC1-6/s
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Page/Page column 30
(2010/11/28)
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- Economical manufacturing process for 1,2,3-triazoles
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A high quality 1,2,3-triazole is obtained in a one pot two step reaction between appropriately substituted hydrazide derivatives, dihaloethanediol and NH3 in methanol. Synthesis of various N1 -alkyl, N1 -aryl, and N1
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