ethyl 3-(5-(4-bromophenyl)-1-(4-carbamoyl-2-methylphenyl)-1H-pyrrol-2-yl)propanoate | 1208318-09-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: ethyl 3-(5-(4-bromophenyl)-1-(4-carbamoyl-2-methylphenyl)-1H-pyrrol-2-yl)propanoate
• 英文别名: Ethyl 3-[5-(4-bromophenyl)-1-(4-carbamoyl-2-methylphenyl)pyrrol-2-yl]propanoate
• CAS: 1208318-09-5
• 化学式: C₂₃H₂₃BrN₂O₃
• 分子量: 455.351
• InChiKey: GHOQWDYELSSTBQ-UHFFFAOYSA-N

物化性质

• 沸点：
  572.3±50.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  74.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 3-(5-(4-bromophenyl)-1-(4-carbamoyl-2-methylphenyl)-1H-pyrrol-2-yl)propanoate 在 copper(l) iodide 、 lithium hydroxide monohydrate 、 水 、 potassium carbonate 、 L-脯氨酸 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 反应 5.0h， 生成 N6022抑制剂
  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
• 作为产物：
  描述：

  3-methyl-4-(1H-pyrrol-1-yl)benzamide 在 N-溴代丁二酰亚胺(NBS) 、 四(三苯基膦)钯 、 palladium 10% on activated carbon 、 氢气 、 双氧水 、 sodium carbonate 、 potassium carbonate 、 三氯氧磷 作用下， 以 乙醇 、 二甲基亚砜 、 甲苯 为溶剂， 生成 ethyl 3-(5-(4-bromophenyl)-1-(4-carbamoyl-2-methylphenyl)-1H-pyrrol-2-yl)propanoate
  参考文献：
  名称：

  Discovery of S-Nitrosoglutathione Reductase Inhibitors: Potential Agents for the Treatment of Asthma and Other Inflammatory Diseases

  摘要：

  S-Nitrosoglutathione reductase (GSNOR) regulates S-nitrosothiols (SNOs) and nitric oxide (NO) in vivo through catabolism of S-nitrosoglutathione (GSNO). GSNOR and the anti-inflammatory and smooth muscle relaxant activities of SNOs, GSNO, and NO play significant roles in pulmonary, cardiovascular, and gastrointestinal function. In GSNOR knockout mice, basal airway tone is reduced and the response to challenge with bronchoconstrictors or airway allergens is attenuated. Consequently, GSNOR has emerged as an attractive therapeutic target for several clinically important human diseases. As such, small molecule inhibitors of GSNOR were developed. These GSNOR inhibitors were potent, selective, and efficacious in animal models of inflammatory disease characterized by reduced levels of GSNO and bioavailable NO. N6022, a potent and reversible GSNOR inhibitor, reduced bronchoconstriction and pulmonary inflammation in a mouse model of asthma and demonstrated an acceptable safety profile. N6022 is currently in clinical development as a potential agent for the treatment of acute asthma.

  DOI：

  10.1021/ml200045s

文献信息

• [EN] NOVEL PYRROLE INHIBITORS OF S-NITROSOGLUTATHIONE REDUCTASE AS THERAPEUTIC AGENTS<br/>[FR] NOUVEAUX INHIBITEURS PYRROLIQUES DE LA S-NITROSOGLUTATHION RÉDUCTASE EN TANT QU'AGENTS THÉRAPEUTIQUES
  申请人：N30 PHARMACEUTICALS LLC

  公开号：WO2010019910A1

  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，包括这种GSNOR抑制剂的制药组合物，以及制备和使用它们的方法。
• [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。
• Discovery of potent and novel S-nitrosoglutathione reductase inhibitors devoid of cytochrome P450 activities
  作者：Xicheng Sun、Jian Qiu、Sarah A. Strong、Louis S. Green、Jan W.F. Wasley、Joan P. Blonder、Dorothy B. Colagiovanni、Sarah C. Mutka、Adam M. Stout、Jane P. Richards、Gary J. Rosenthal

  DOI：10.1016/j.bmcl.2011.07.103

  日期：2011.10

  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.
• ACS Med. Chem. Lett. 2011, 2, 402-406
  作者：

  DOI：——

  日期：——