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MedKoo CAT#: 510280
CAS#: 1208315-24-5
Description: N6022 is 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).
MedKoo Cat#: 510280
Name: N6022
CAS#: 1208315-24-5
Chemical Formula: C24H22N4O3
Exact Mass: 414.16919
Molecular Weight: 414.46
Elemental Analysis: C, 69.55; H, 5.35; N, 13.52; O, 11.58
Synonym: N6022; N-6022; N 6022.
IUPAC/Chemical Name: 3-(5-(4-(1H-imidazol-1-yl)phenyl)-1-(4-carbamoyl-2-methylphenyl)-1H-pyrrol-2-yl)propanoic acid
InChi Key: YVPGZQLRPAGKLA-UHFFFAOYSA-N
InChi Code: InChI=1S/C24H22N4O3/c1-16-14-18(24(25)31)4-9-21(16)28-20(8-11-23(29)30)7-10-22(28)17-2-5-19(6-3-17)27-13-12-26-15-27/h2-7,9-10,12-15H,8,11H2,1H3,(H2,25,31)(H,29,30)
SMILES Code: O=C(O)CCC1=CC=C(C2=CC=C(N3C=CN=C3)C=C2)N1C4=CC=C(C(N)=O)C=C4C
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. N6022 was demonstrated efficacy in a mouse ovalbumin (OVA) model of asthma. (Bioorg Med Chem Lett. 2011 Oct 1;21(19):5849-53)
1: Blonder JP, Mutka SC, Sun X, Qiu J, Green LH, Mehra NK, Boyanapalli R, Suniga M, Look K, Delany C, Richards JP, Looker D, Scoggin C, Rosenthal GJ. Pharmacologic inhibition of S-nitrosoglutathione reductase protects against experimental asthma in BALB/c mice through attenuation of both bronchoconstriction and inflammation. BMC Pulm Med. 2014 Jan 10;14:3. doi: 10.1186/1471-2466-14-3. PubMed PMID: 24405692; PubMed Central PMCID: PMC3893392.
2: Sun X, Qiu J, Strong SA, Green LS, Wasley JW, Blonder JP, Colagiovanni DB, Stout AM, Mutka SC, Richards JP, Rosenthal GJ. Structure-activity relationship of pyrrole based S-nitrosoglutathione reductase inhibitors: carboxamide modification. Bioorg Med Chem Lett. 2012 Mar 15;22(6):2338-42. doi: 10.1016/j.bmcl.2012.01.047. Epub 2012 Feb 2. PubMed PMID: 22342142.
3: Green LS, Chun LE, Patton AK, Sun X, Rosenthal GJ, Richards JP. Mechanism of inhibition for N6022, a first-in-class drug targeting S-nitrosoglutathione reductase. Biochemistry. 2012 Mar 13;51(10):2157-68. doi: 10.1021/bi201785u. Epub 2012 Feb 28. PubMed PMID: 22335564.
4: Colagiovanni DB, Drolet DW, Langlois-Forget E, Piché MP, Looker D, Rosenthal GJ. A nonclinical safety and pharmacokinetic evaluation of N6022: a first-in-class S-nitrosoglutathione reductase inhibitor for the treatment of asthma. Regul Toxicol Pharmacol. 2012 Feb;62(1):115-24. doi: 10.1016/j.yrtph.2011.12.012. Epub 2011 Dec 24. PubMed PMID: 22210450.
5: Sun X, Qiu J, Strong SA, Green LS, Wasley JW, Blonder JP, Colagiovanni DB, Mutka SC, Stout AM, Richards JP, Rosenthal GJ. Discovery of potent and novel S-nitrosoglutathione reductase inhibitors devoid of cytochrome P450 activities. Bioorg Med Chem Lett. 2011 Oct 1;21(19):5849-53. doi: 10.1016/j.bmcl.2011.07.103. Epub 2011 Aug 3. PubMed PMID: 21855338.
6: Sun X, Qiu J, Strong SA, Green LS, Wasley JW, Colagiovanni DB, Mutka SC, Blonder JP, Stout AM, Richards JP, Chun L, Rosenthal GJ. Structure-activity relationships of pyrrole based S-nitrosoglutathione reductase inhibitors: pyrrole regioisomers and propionic acid replacement. Bioorg Med Chem Lett. 2011 Jun 15;21(12):3671-5. doi: 10.1016/j.bmcl.2011.04.086. Epub 2011 Apr 24. PubMed PMID: 21570838.
