methyl 3-amino-5-(4-cyanophenyl)thiophene-2-carboxylate | 887247-31-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: methyl 3-amino-5-(4-cyanophenyl)thiophene-2-carboxylate
• 英文别名: Methyl 3-amino-5-(4-cyanophenyl)-2-thiophenecarboxylate
• CAS: 887247-31-6
• 化学式: C₁₃H₁₀N₂O₂S
• 分子量: 258.301
• InChiKey: AEMJBZUOFVMJAC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  104
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 3-amino-5-(4-cyanophenyl)thiophene-2-carboxylate 在 苯酚 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.5h， 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：

  5-溴-3-(2,2,2-三氟-乙酰基氨基)-噻吩-2-羧酸甲酯 在 水 、 palladium diacetate 、 sodium carbonate 、 potassium carbonate 、 三苯基膦 作用下， 以 1,4-二氧六环 、 甲醇 、 水 为溶剂， 反应 2.0h， 生成 methyl 3-amino-5-(4-cyanophenyl)thiophene-2-carboxylate
  参考文献：
  名称：

  N-烷基-4-烷基氨基-6-芳基噻吩并[3,2 - d ]嘧啶-2-甲酰胺衍生物的固相合成方法

  摘要：

  在此，我们描述了一种用于合成N-烷基-4-烷基氨基-6-芳基噻吩并[3,2 - d ]嘧啶-2-甲酰胺衍生物的固相合成方法。这些衍生物由具有生物活性的 6-苯基噻吩并[3,2- d ]嘧啶支架组成。模板介导的合成策略涉及 3-氨基-5-溴噻吩-2-羧酸甲酯和芳基硼酸之间的 Suzuki 偶联反应，得到 3-氨基-5-芳基噻吩-2-羧酸甲酯。涉及 3-氨基-5-芳基噻吩-2-羧酸甲酯和氰基甲酸甲酯的环缩合反应生成酯，当进行水解反应时生成 6-芳基-4-氧代-3,4-二氢噻吩[3,2- d]嘧啶-2-羧酸（模板化合物）。这些羧酸模板与负载伯烷基胺的酸敏感甲氧基苯甲醛 (AMEBA) 树脂偶联。酰胺偶联反应之后是由苯并三唑-1-基氧基三（二甲氨基）鏻六氟磷酸盐 (BOP) 介导的直接胺化反应。随后将化合物从固体载体上裂解下来，使用反相高效液相色谱技术 (RP-HPLC) 进行纯化，然后通过用水预处理的强阴离子交换

  DOI：

  10.1016/j.tet.2021.132247

文献信息

• Glycogen Phosphorylase Inhibitor Compounds and Pharmaceutical Compositions Thereof
  申请人：Evans Karen

  公开号：US20070249670A1

  公开（公告）日：2007-10-25

  The invention relates to glycogen phosphorylase inhibitor compounds, pharmaceutical compositions of these compounds, methods of treatment using the pharmaceutical compositions to treat diabetes, conditions associated with diabetes, and/or tissue ischemia, including myocardial ischemia, and processes for making the compounds.

  本发明涉及糖原磷酸化酶抑制剂化合物、这些化合物的药物组合物、使用这些药物组合物治疗糖尿病、与糖尿病相关的疾病和/或组织缺血，包括心肌缺血的方法，以及制备这些化合物的过程。
• 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.
• GLYCOGEN PHOSPHORYLASE INHIBITOR COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF
  申请人：SMITHKLINE BEECHAM CORPORATION

  公开号：EP1812383A1

  公开（公告）日：2007-08-01
• [EN] GLYCOGEN PHOSPHORYLASE INHIBITOR COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF<br/>[FR] COMPOSES INHIBITEURS DE LA PHOSPHORYLASE DU GLYCOGENE ET COMPOSITIONS PHARMACEUTIQUES LES COMPRENANT
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2006052722A1

  公开（公告）日：2006-05-18

  [EN] The invention relates to glycogen phosphorylase inhibitor compounds, pharmaceutical compositions of these compounds, methods of treatment using the pharmaceutical compositions to treat diabetes, conditions associated with diabetes, and/or tissue ischemia, including myocardial ischemia, and processes for making the compounds.
  [FR] L'invention concerne des composés inhibiteurs de la phosphorylase de glycogène, des compositions pharmaceutiques contenant lesdits composés, des méthodes de traitement utilisées pour traiter le diabète, des états pathologiques associés au diabète et/ou à l'ischémie des tissus, notamment l'ischémie myocardique, et des procédés pour fabriquer les composés de l'invention.