5-(1,1,1,3,3,3-六氟-2-羟基丙烷-2-基)-4,5-二氢异噁唑-3-羧酸 | 444342-51-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑啉类
• 中文名称: 5-(1,1,1,3,3,3-六氟-2-羟基丙烷-2-基)-4,5-二氢异噁唑-3-羧酸
• 英文名称: 5-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]-4,5-dihydroisoxazole-3-carboxylic acid
• 英文别名: 5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-4,5-dihydroisoxazole-3-carboxylic acid；5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-4,5-dihydro-1,2-oxazole-3-carboxylic acid
• CAS: 444342-51-2
• 化学式: C₇H₅F₆NO₄
• 分子量: 281.111
• InChiKey: IBMVCDLJFNIKPH-UHFFFAOYSA-N

物化性质

• 沸点：
  332.5±52.0 °C(Predicted)
• 密度：
  1.83±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  79.1
• 氢给体数：
  2
• 氢受体数：
  11

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  5-(1,1,1,3,3,3-六氟-2-羟基丙烷-2-基)-4,5-二氢异噁唑-3-羧酸 、 L-苯基丙氨酸叔丁酯 在 N-甲基吗啉 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (2S)-tert-butyl 2-(5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-4,5-dihydroisoxazole-3-carboxamido)-3-phenylpropanoate
  参考文献：
  名称：

  Discovery of Potent and Orally Available Malonyl-CoA Decarboxylase Inhibitors as Cardioprotective Agents

  摘要：

  Discovery of 5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2yl)-4,5-dihydroisoxazole-3-carboxamides as a new class of malonyl-coenzyme A decarboxylase (MCD) inhibitors is described. tert-Butyl 3-(5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-4,5-dihydroisoxazole-3-carboxamido) butanoate (5, CBM-301940) exhibited excellent potency and in vivo PK/ADME properties. It is the most powerful stimulant of glucose oxidation reported to date in isolated working rat hearts. Compound 5 improved the cardiac efficiency and function in a rat heart global ischemia/reperfusion model, suggesting MCD inhibitors may be useful for the treatment of ischemic heart diseases.

  DOI：

  10.1021/jm0605029
• 作为产物：
  描述：

  2-乙烯基六氟异丙醇 在 sodium hydroxide 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 69.0h， 生成 5-(1,1,1,3,3,3-六氟-2-羟基丙烷-2-基)-4,5-二氢异噁唑-3-羧酸
  参考文献：
  名称：

  Discovery of Potent and Orally Available Malonyl-CoA Decarboxylase Inhibitors as Cardioprotective Agents

  摘要：

  Discovery of 5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2yl)-4,5-dihydroisoxazole-3-carboxamides as a new class of malonyl-coenzyme A decarboxylase (MCD) inhibitors is described. tert-Butyl 3-(5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-4,5-dihydroisoxazole-3-carboxamido) butanoate (5, CBM-301940) exhibited excellent potency and in vivo PK/ADME properties. It is the most powerful stimulant of glucose oxidation reported to date in isolated working rat hearts. Compound 5 improved the cardiac efficiency and function in a rat heart global ischemia/reperfusion model, suggesting MCD inhibitors may be useful for the treatment of ischemic heart diseases.

  DOI：

  10.1021/jm0605029

文献信息

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

  公开号：US20040082576A1

  公开（公告）日：2004-04-29

  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.

  本发明涉及新颖化合物（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制药组合物，用于治疗某些代谢疾病和受酰辅酶A丙酮酸羧化酶（丙酮酸辅酶A羧化酶，MCD）抑制调节的疾病。具体而言，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预防、管理和治疗心血管疾病、糖尿病、酸中毒、癌症和肥胖症。
• HETEROCYCLIC CETP INHIBITORS
  申请人：Salvati E. Mark

  公开号：US20070135631A1

  公开（公告）日：2007-06-14

  Compounds of formula Ia and Ib wherein A, B, C and R 1 are described herein.

  公式Ia和Ib的化合物，其中A、B、C和R1如下所述。
• Malonyl-CoA Decarboxylase Inhibitors Useful as Metabolic Modulators
  申请人：Arrhenius Thomas

  公开号：US20100016259A1

  公开（公告）日：2010-01-21

  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)及其前药，以及药学上可接受的盐和含有这种化合物的制剂。这些化合物在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)抑制调节的疾病方面有用。具体而言，本发明涉及化合物和制剂以及通过抑制受酰辅酶A丙酮酸羧化酶的预防、管理和治疗心血管疾病、糖尿病、酸中毒、癌症和肥胖症的方法。
• Malonyl-CoA decarboxylase inhibitors useful as metabolic modulators
  申请人：Chugai Seiyaku Kabushiki Kaisha

  公开号：US07524969B2

  公开（公告）日：2009-04-28

  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，以及包含这些化合物的药物组合物，在治疗某些代谢性疾病和通过抑制麦芽酰辅酶A脱羧酶（麦芽酰辅酶CoA脱羧酶，MCD）酶调节的疾病方面有用。特别是，本发明涉及化合物和组合物以及通过抑制麦芽酰辅酶A脱羧酶预防、管理和治疗心血管疾病、糖尿病、酸中毒、癌症和肥胖症的方法。
• WO2007/62308
  申请人：——

  公开号：——

  公开（公告）日：——