3-[1-(4-carbamoyl-2-methylphenyl)-5-(4-[1,2,3]triazol-1-ylphenyl)-1H-pyrrol-2-yl]propionic acid ethyl ester | 1208318-26-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 3-[1-(4-carbamoyl-2-methylphenyl)-5-(4-[1,2,3]triazol-1-ylphenyl)-1H-pyrrol-2-yl]propionic acid ethyl ester
• 英文别名: 3-[1-(4-carbamoyl-2-methylphenyl)-5-(4-[1,2,3]triazo1-1-ylphenyl)-1H-pyrrol-2-yl]propionic acid ethyl ester；3-[1-(4-carbamoyl-2-methylphenyl)-5-(4-[1,2,3]triazol-1-yl-phenyl)-1H-pyrrol-2-yl]-propionic acid ethyl ester；ethyl 3-[1-(4-carbamoyl-2-methylphenyl)-5-[4-(triazol-1-yl)phenyl]pyrrol-2-yl]propanoate
• CAS: 1208318-26-6
• 化学式: C₂₅H₂₅N₅O₃
• 分子量: 443.505
• InChiKey: JJYWLFYFKDTMTG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-[1-(4-carbamoyl-2-methylphenyl)-5-(4-[1,2,3]triazol-1-ylphenyl)-1H-pyrrol-2-yl]propionic acid ethyl ester 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 18.0h， 以25%的产率得到3-[1-(4-carbamoyl-2-methylphenyl)-5-(4-[1,2,3]triazol-1-ylphenyl)-1H-pyrrol-2-yl]propionic acid
  参考文献：
  名称：

  Discovery of potent and novel S-nitrosoglutathione reductase inhibitors devoid of cytochrome P450 activities

  摘要：

  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. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.07.103
• 作为产物：
  描述：

  3-[1-(4-carbamoyl-2-methylphenyl)-5-(4-nitrophenyl)-1H-pyrrole-2-yl]propanoic acid ethyl ester 在 palladium 10% on activated carbon 、 甲酸铵 、 三乙胺 作用下， 以 甲醇 为溶剂， 反应 47.0h， 生成 3-[1-(4-carbamoyl-2-methylphenyl)-5-(4-[1,2,3]triazol-1-ylphenyl)-1H-pyrrol-2-yl]propionic acid ethyl ester
  参考文献：
  名称：

  Pyrrole inhibitors of S-nitrosoglutathione reductase as therapeutic agents

  摘要：

  本发明涉及S-亚硝基谷胱甘肽还原酶（GSNOR）的抑制剂，包括这种GSNOR抑制剂的药物组合物，以及制备和使用这些药物的方法。

  公开号：

  US09138427B2

文献信息

• Pyrrole inhibitors of S-nitrosoglutathione reductase as therapeutic agents
  申请人：N30 Pharmaceuticals, Inc.

  公开号：US09138427B2

  公开（公告）日：2015-09-22

  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.

  本发明涉及S-亚硝基谷胱甘肽还原酶（GSNOR）的抑制剂，包括这种GSNOR抑制剂的药物组合物，以及制备和使用这些药物的方法。
• [EN] NOVEL PYRROLE INHIBITORS OF S-NITROSOGLUTATHIONE REDUCTASE AS THERAPEUTIC AGENTS<br/>[FR] NOUVEAUX INHIBITEURS PYRROLE DE S-NITROSOGLUTATHIONE RÉDUCTASE EN TANT QU'AGENTS THÉRAPEUTIQUES
  申请人：N30 PHARMACEUTICALS LLC

  公开号：WO2010019903A1

  公开（公告）日：2010-02-18

  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.

  本发明涉及S-亚硝基谷胱甘肽还原酶（GSNOR）的抑制剂，包括这样的GSNOR抑制剂的制药组合物，以及制备和使用这些组合物的方法。
• Novel Pyrrole Inhibitors of S-Nitrosoglutathione Reductase as Therapeutic Agents
  申请人：Wasley Jan

  公开号：US20110144110A1

  公开（公告）日：2011-06-16

  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.

  本发明涉及S-亚硝基谷胱甘肽还原酶（GSNOR）的抑制剂，包括这种GSNOR抑制剂的药物组合物，以及制备和使用它们的方法。
• NOVEL PYRROLE INHIBITORS OF S-NITROSOGLUTATHIONE REDUCTASE AS THERAPEUTIC AGENTS
  申请人：N30 Pharmaceuticals, LLC

  公开号：EP2318006A1

  公开（公告）日：2011-05-11
• US8691816B2
  申请人：——

  公开号：US8691816B2

  公开（公告）日：2014-04-08