ethyl 5-(4-chlorophenyl)-2-methyl-1-(4-sulfamoylphenyl)-1H-pyrrole-3-carboxylate | 889767-08-2

• 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 5-(4-chlorophenyl)-2-methyl-1-(4-sulfamoylphenyl)-1H-pyrrole-3-carboxylate
• 英文别名: ethyl 5-(4-chlorophenyl)-2-methyl-1-(4-sulfamoylphenyl)pyrrole-3-carboxylate
• CAS: 889767-08-2
• 化学式: C₂₀H₁₉ClN₂O₄S
• 分子量: 418.901
• InChiKey: NVJJSDYPFZXQGJ-UHFFFAOYSA-N

物化性质

• 熔点：
  113-115 °C(Solv: ethanol (64-17-5))
• 沸点：
  603.0±65.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  99.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 5-(4-chlorophenyl)-2-methyl-1-(4-sulfamoylphenyl)-1H-pyrrole-3-carboxylate 在 水 、 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以2.18 g的产率得到disodium 5-(4-chloro-phenyl)-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylate
  参考文献：
  名称：

  Discovery of 4-(5-(4-Chlorophenyl)-2-methyl-3-propionyl-1H-pyrrol-1-yl)benzenesulfonamide (A-867744) as a Novel Positive Allosteric Modulator of the α7 Nicotinic Acetylcholine Receptor

  摘要：

  The discovery of a series of pyrrole-sulfonamides as positive allosteric modulators (PAM) of alpha 7 nAChRs is described. Optimization of this series led to the identification of 19 (A-867744), a novel type II PAM with good potency and selectivity. Compound 19 showed acceptable pharmacokinetic profile across species and brain levels sufficient to modulate 0 nAChRs. In a rodent model of sensory gating, 19 normalized gating deficits. These results suggest that 19 represents a novel class of molecules capable of allosteric modulation of the 0 nAChRs.

  DOI：

  10.1021/jm9003818
• 作为产物：
  描述：

  2-乙酰基-4-(4-氯苯基)-4-氧代丁酸乙酯 、 磺胺 以 溶剂黄146 为溶剂， 反应 48.0h， 生成 ethyl 5-(4-chlorophenyl)-2-methyl-1-(4-sulfamoylphenyl)-1H-pyrrole-3-carboxylate
  参考文献：
  名称：

  Discovery of 4-(5-(4-Chlorophenyl)-2-methyl-3-propionyl-1H-pyrrol-1-yl)benzenesulfonamide (A-867744) as a Novel Positive Allosteric Modulator of the α7 Nicotinic Acetylcholine Receptor

  摘要：

  The discovery of a series of pyrrole-sulfonamides as positive allosteric modulators (PAM) of alpha 7 nAChRs is described. Optimization of this series led to the identification of 19 (A-867744), a novel type II PAM with good potency and selectivity. Compound 19 showed acceptable pharmacokinetic profile across species and brain levels sufficient to modulate 0 nAChRs. In a rodent model of sensory gating, 19 normalized gating deficits. These results suggest that 19 represents a novel class of molecules capable of allosteric modulation of the 0 nAChRs.

  DOI：

  10.1021/jm9003818

文献信息

• Heteromeric Neuronal Nicotinic Acetylcholine Receptors with Mutant <i>β</i> Subunits Acquire Sensitivity to <i>α</i>7-Selective Positive Allosteric Modulators
  作者：Clare Stokes、Sumanta Garai、Abhijit R. Kulkarni、Lucas N. Cantwell、Colleen M. Noviello、Ryan E. Hibbs、Nicole A. Horenstein、Khalil A. Abboud、Ganesh A. Thakur、Roger L. Papke

  DOI：10.1124/jpet.119.259499

  日期：2019.8

  Homomeric α7 nicotinic acetylcholine receptors (nAChR) have an intrinsically low probability of opening that can be overcome by α7-selective positive allosteric modulators (PAMs), which bind at a site involving the second transmembrane domain (TM2). Mutation of a methionine that is unique to α7 at the 15' position of TM2 to leucine, the residue in most other nAChR subunits, largely eliminates the activity

  同源的α7烟碱乙酰胆碱受体（nAChR）本质上具有较低的打开可能性，可以通过α7选择性正构构变数（PAM）克服，后者在涉及第二个跨膜结构域（TM2）的位点结合。在大多数其他nAChR亚基中的残基，TM2的15'位置上的α7特有的甲硫氨酸突变为亮氨酸，很大程度上消除了此类PAM的活性。我们测试了反向突变（L15'M）在含有α4和β2（这是大脑中最丰富的nAChR亚基）的异聚nAChR受体中的作用。发现含有这些突变的受体被α7PAM 3a，4,5,9b-四氢-4-（1-萘基）-3H-环戊烷[c]喹啉-8-磺酰胺（TQS）强烈增强，但对它们不敏感。替代PAM 1-（5-chloro-2，4-二甲氧基苯基）-3-（5-甲基异恶唑-3-基）-脲。对于TQS敏感性，β2亚基中突变的存在是必要和充分的。α4亚基突变的主要作用是减少对单独应用的乙酰胆碱的反应。对TQS的敏感性仅需要单个突变体β亚基，而不管
• PYRROLE DERIVATIVES AND THEIR METHODS OF USE
  申请人：Faghih Ramin

  公开号：US20080064695A1

  公开（公告）日：2008-03-13

  The invention relates to a series of substituted pyrrole derivatives, compositions comprising the same, and methods of treating conditions and disorders using such compounds and compositions.

  本发明涉及一系列取代吡咯衍生物，包括这些衍生物的组合物以及使用这些化合物和组合物治疗疾病和疾病的方法。
• Pyrrole Derivatives and Their Methods of Use
  申请人：Faghih Ramin

  公开号：US20100216748A1

  公开（公告）日：2010-08-26

  The invention relates to a series of substituted pyrrole derivatives, compositions comprising the same, and methods of treating conditions and disorders using such compounds and compositions.

  本发明涉及一系列取代吡咯衍生物，包括这些衍生物的组合物以及使用这些化合物和组合物治疗疾病和障碍的方法。
• WO2008/2974
  申请人：——

  公开号：——

  公开（公告）日：——
• US7741364B2
  申请人：——

  公开号：US7741364B2

  公开（公告）日：2010-06-22