5-Methyl-4-[4-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-phenyl]-isoxazole-3-carboxylic acid ethyl ester | 449803-28-5

• 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-Methyl-4-[4-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-phenyl]-isoxazole-3-carboxylic acid ethyl ester
• 英文别名: ethyl 4-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-5-methyl-1,2-oxazole-3-carboxylate
• CAS: 449803-28-5
• 化学式: C₁₆H₁₃F₆NO₄
• 分子量: 397.274
• InChiKey: RFNJTAVYNOVWTB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  72.6
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  5-Methyl-4-[4-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-phenyl]-isoxazole-3-carboxylic acid ethyl ester 在 4-二甲氨基吡啶 、 sodium hydroxide 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 生成 4-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-N-methoxy-N,5-dimethyl-1,2-oxazole-3-carboxamide
  参考文献：
  名称：

  Design and synthesis of heterocyclic malonyl-CoA decarboxylase inhibitors

  摘要：

  We have previously reported the discovery of small molecule inhibitors of malonyl-CoA decarboxylase (MCD) as novel metabolic modulators, which inhibited fatty acid oxidation and consequently increased the glucose oxidation rates in the isolated working rat hearts. MCD inhibitors were also shown to improve cardiac efficiency in rat and pig demand-induced ischemic models through the mechanism-based modulation of energy metabolism. Herein, we describe the design and synthesis of a series of novel heterocyclic MCD inhibitors with a preference for substituted imidazole and isoxazole. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.10.020
• 作为产物：
  描述：

  2-(4-bromophenyl)-1,1,1,3,3,3-hexafluoropropan-2-ol 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium acetate 、 碳酸氢钠 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 5-Methyl-4-[4-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-phenyl]-isoxazole-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  Design and synthesis of heterocyclic malonyl-CoA decarboxylase inhibitors

  摘要：

  We have previously reported the discovery of small molecule inhibitors of malonyl-CoA decarboxylase (MCD) as novel metabolic modulators, which inhibited fatty acid oxidation and consequently increased the glucose oxidation rates in the isolated working rat hearts. MCD inhibitors were also shown to improve cardiac efficiency in rat and pig demand-induced ischemic models through the mechanism-based modulation of energy metabolism. Herein, we describe the design and synthesis of a series of novel heterocyclic MCD inhibitors with a preference for substituted imidazole and isoxazole. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.10.020

文献信息

• Malonyl-coa decarboxylase inhibitors useful as metabolic modulators
  申请人：——

  公开号：US20040063671A1

  公开（公告）日：2004-04-01

  The present invention relates to novel compounds (I), their prodrugs, and the pharmaceutically acceptable salts as well as pharmaceutical compositions containing such compounds useful in treating certain metabolic diseases and diseases modulated by the inhibition of the enzyme malonyl-coenzyme A decarboxylase (malonyl-CoA decarboxylase, MCD). In particular, the invention relates to compounds and compositions and the methods for the prophylaxis, management and treatment of cardiovascular diseases, diabetes, acidosis, cancers, and obesity through the inhibition of malonyl-coenzyme A decarboxylase. 1

  本发明涉及新型化合物（I）、它们的前药和药物可接受的盐，以及包含这些化合物的药物组合物，用于治疗某些代谢性疾病和受酰辅酶A丙酮酸羧化酶（malonyl-CoA decarboxylase，MCD）抑制影响的疾病。特别是，本发明涉及化合物和组合物以及通过抑制受酰辅酶A丙酮酸羧化酶的方法进行心血管疾病、糖尿病、酸中毒、癌症和肥胖症的预防、管理和治疗。
• Malonyl-CoA Decarboxylase Inhibitors Useful as Metabolic Modulators
  申请人：Arrhenius Thomas

  公开号：US20080070869A1

  公开（公告）日：2008-03-20

  The present invention relates to novel compounds (I), their prodrugs, and the pharmaceutically acceptable salts as well as pharmaceutical compositions containing such compounds useful in treating certain metabolic diseases and diseases modulated by the inhibition of the enzyme malonyl-coenzyme A decarboxylase (malonyl-CoA decarboxylase, MCD). In particular, the invention relates to compounds and compositions and the methods for the prophylaxis, management and treatment of cardiovascular diseases, diabetes, acidosis, cancers, and obesity through the inhibition of malonyl-coenzyme A decarboxylase.

  本发明涉及新型化合物(I)、它们的前药以及药学上可接受的盐，以及含有这种化合物的药物组合物，用于治疗某些代谢性疾病和通过抑制麦芽酰辅酶A脱羧酶(malonyl-CoA decarboxylase，MCD)酶的抑制而调节的疾病。特别地，本发明涉及化合物和组合物，以及通过抑制麦芽酰辅酶A脱羧酶的方法预防、管理和治疗心血管疾病、糖尿病、酸中毒、癌症和肥胖症。
• MALONYL-COA DECARBOXYLASE INHIBITORS USEFUL AS METABOLIC MODULATORS
  申请人：CHUGAI SEIYAKU KABUSHIKI KAISHA

  公开号：EP1377290B1

  公开（公告）日：2006-10-04
• US7279477B2
  申请人：——

  公开号：US7279477B2

  公开（公告）日：2007-10-09
• Design and synthesis of heterocyclic malonyl-CoA decarboxylase inhibitors
  作者：Jie-Fei Cheng、Mi Chen、Bin Liu、Zheng Hou、Thomas Arrhenius、Alex M. Nadzan

  DOI：10.1016/j.bmcl.2005.10.020

  日期：2006.2

  We have previously reported the discovery of small molecule inhibitors of malonyl-CoA decarboxylase (MCD) as novel metabolic modulators, which inhibited fatty acid oxidation and consequently increased the glucose oxidation rates in the isolated working rat hearts. MCD inhibitors were also shown to improve cardiac efficiency in rat and pig demand-induced ischemic models through the mechanism-based modulation of energy metabolism. Herein, we describe the design and synthesis of a series of novel heterocyclic MCD inhibitors with a preference for substituted imidazole and isoxazole. (c) 2005 Elsevier Ltd. All rights reserved.