methyl 5-(4-cyanophenyl)-3-{[(1E)-(dimethylamino)methylidene]amino}-2-thiophenecarboxylate | 917597-45-6

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: methyl 5-(4-cyanophenyl)-3-{[(1E)-(dimethylamino)methylidene]amino}-2-thiophenecarboxylate
• CAS: 917597-45-6
• 化学式: C₁₆H₁₅N₃O₂S
• 分子量: 313.38
• InChiKey: WLNIGOSYZPXOGX-VCHYOVAHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.29
• 重原子数：
  22.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  65.69
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  3-甲氧基-4-[2-(1-吡咯烷)乙氧基]苯胺 、 methyl 5-(4-cyanophenyl)-3-{[(1E)-(dimethylamino)methylidene]amino}-2-thiophenecarboxylate 在 苯酚 作用下， 反应 1.5h， 生成 4-{3-[3-Methoxy-4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-4-oxo-3,4-dihydro-thieno[3,2-d]pyrimidin-6-yl}-benzonitrile
  参考文献：
  名称：

  The discovery and optimization of pyrimidinone-containing MCH R1 antagonists

  摘要：

  Optimization of a series of constrained melanin-concentrating hormone receptor 1 (MCH RI) antagonists has provided compounds with potent and selective MCH R1 activity. Details of the optimization process are provided and the use of one of the compounds in an animal model of diet-induced obesity is presented. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.07.008
• 作为产物：
  描述：

  对氰基苯乙酮 在 sodium methylate 、 三氯氧磷 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 17.17h， 生成 methyl 5-(4-cyanophenyl)-3-{[(1E)-(dimethylamino)methylidene]amino}-2-thiophenecarboxylate
  参考文献：
  名称：

  The discovery and optimization of pyrimidinone-containing MCH R1 antagonists

  摘要：

  Optimization of a series of constrained melanin-concentrating hormone receptor 1 (MCH RI) antagonists has provided compounds with potent and selective MCH R1 activity. Details of the optimization process are provided and the use of one of the compounds in an animal model of diet-induced obesity is presented. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.07.008

文献信息

• Potent, Selective, and Orally Efficacious Antagonists of Melanin-Concentrating Hormone Receptor 1
  作者：Francis X. Tavares、Kamal A. Al-Barazanji、Eric C. Bigham、Michael J. Bishop、Christy S. Britt、David L. Carlton、Paul L. Feldman、Aaron S. Goetz、Mary K. Grizzle、Yu C. Guo、Anthony L. Handlon、Donald L. Hertzog、Diane M. Ignar、Daniel G. Lang、Ronda J. Ott、Andrew J. Peat、Hui-Qiang Zhou

  DOI：10.1021/jm060572f

  日期：2006.11.30

  The high expression of MCH in the hypothalamus with the lean hypophagic phenotype coupled with increased resting metabolic rate and resistance to high fat diet-induced obesity of MCH KO mice has spurred considerable efforts to develop small molecule MCHR1 antagonists. Starting from a lead thienopyrimidinone series, structure-activity studies at the 3- and 6-positions of the thienopyrimidinone core afforded potent and selective MCHR1 antagonists with representative examples having suitable pharmacokinetic properties. Based on structure-activity relationships, a structural model for MCHR1 was constructed to explain the binding mode of these antagonists. In general, a good correlation was observed between pK(a)s and activity in the right-hand side of the template, with Asp123 playing an important role in the enhancement of binding affinity. A representative example when evaluated chronically in diet-induced obese mice resulted in good weight loss effects. These antagonists provide a viable lead series in the discovery of new therapies for the treatment of obesity.