5-(p-trifluoromethylphenyl)-3-amino-2-thiophenecarboxylic acid methyl ester | 150359-99-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-(p-trifluoromethylphenyl)-3-amino-2-thiophenecarboxylic acid methyl ester
• 英文别名: Methyl 3-amino-5-(4-(trifluoromethyl)phenyl)thiophene-2-carboxylate；Methyl 3-amino-5-[4-(trifluoromethyl)phenyl]thiophene-2-carboxylate
• CAS: 150359-99-2
• 化学式: C₁₃H₁₀F₃NO₂S
• 分子量: 301.289
• InChiKey: ZTADOTAPVMECKG-UHFFFAOYSA-N

物化性质

• 沸点：
  425.8±45.0 °C(Predicted)
• 密度：
  1.382±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  80.6
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5-(p-trifluoromethylphenyl)-3-amino-2-thiophenecarboxylic acid methyl ester 在 苯酚 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.5h， 生成 3-[3-Methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]-6-[4-(trifluoromethyl)phenyl]thieno[3,2-d]pyrimidin-4-one
  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：

  4'-三氟甲基苯乙酮 在 sodium methylate 、 三氯氧磷 作用下， 以 甲醇 为溶剂， 反应 2.17h， 生成 5-(p-trifluoromethylphenyl)-3-amino-2-thiophenecarboxylic acid methyl ester
  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.
• Novel small molecule inhibitors targeting the “switch region” of bacterial RNAP: Structure-based optimization of a virtual screening hit
  作者：J. Henning Sahner、Matthias Groh、Matthias Negri、Jörg Haupenthal、Rolf W. Hartmann

  DOI：10.1016/j.ejmech.2013.04.060

  日期：2013.7

  Rising resistance against current antibiotics necessitates the development of antibacterial agents with alternative targets. The "switch region" of RNA polymerase (RNAP), addressed by the myxopyronins, could be such a novel target site. Based on a hit candidate discovered by virtual screening, a small library of 5-phenyl-3-ureidothiophene-2-carboxylic acids was synthesized resulting in compounds with increased RNAP inhibition. Hansch analysis revealed pi (lipophilicity constant) and sigma (Hammet substituent constant) of the substituents at the 5-phenyl moiety to be crucial for activity. The binding mode was proven by the targeted introduction of a moiety mimicking the enecarbamate side chain of myxopyronin into the hit compound, accompanied by enhanced RNAP inhibitory potency. The new compounds displayed good antibacterial activities against Gram positive bacteria and Gram negative Escherichia coli TolC and a reduced resistance frequency compared to the established antibiotic rifampicin. (C) 2013 Elsevier Masson SAS. All rights reserved.
• The discovery and optimization of pyrimidinone-containing MCH R1 antagonists
  作者：Donald L. Hertzog、Kamal A. Al-Barazanji、Eric C. Bigham、Michael J. Bishop、Christy S. Britt、David L. Carlton、Joel P. Cooper、Alex J. Daniels、Dulce M. Garrido、Aaron S. Goetz、Mary K. Grizzle、Yu C. Guo、Anthony L. Handlon、Diane M. Ignar、Ronda O. Morgan、Andrew J. Peat、Francis X. Tavares、Huiqiang Zhou

  DOI：10.1016/j.bmcl.2006.07.008

  日期：2006.9

  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.
• Structure-Guided Optimization of Small-Molecule Folate Uptake Inhibitors Targeting the Energy-Coupling Factor Transporters
  作者：Alexander F. Kiefer、Spyridon Bousis、Mostafa M. Hamed、Eleonora Diamanti、Jörg Haupenthal、Anna K.H. Hirsch

  DOI：10.1021/acs.jmedchem.1c02114

  日期：2022.7.14