| 1173478-69-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• CAS: 1173478-69-7
• 化学式: C₈H₁₁ClO₃
• 分子量: 190.627
• InChiKey: AAYIVNQHGGVCOZ-IZLXSQMJSA-N

物化性质

• 沸点：
  313.7±35.0 °C(Predicted)
• 密度：
  1.316±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.64
• 重原子数：
  12.0
• 可旋转键数：
  2.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  54.37
• 氢给体数：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 1.33h， 生成 4-Chlorocarbonyl-cyclohexanecarboxylic acid benzyl ester
  参考文献：
  名称：

  Discovery of Orally Active Carboxylic Acid Derivatives of 2-Phenyl-5-trifluoromethyloxazole-4-carboxamide as Potent Diacylglycerol Acyltransferase-1 Inhibitors for the Potential Treatment of Obesity and Diabetes

  摘要：

  Diacylglycerol acyltransferase-1 (DGAT-1) is the enzyme that catalyzes the final and committed step of triglyceride formation, namely, the acylation of diacylglycerol with acyl coenzyme A. DGAT-1 deficient mice demonstrate resistance to weight gain on high fat diet, improved insulin sensitivity, and reduced liver triglyceride content. Inhibition of DGAT-1 thus represents a potential novel approach for the treatment of obesity, dyslipidemia, and metabolic syndrome. In this communication, we report the identification of the lead structure 6 and our lead optimization efforts culminating in the discovery of potent, selective, and orally efficacious carboxylic acid derivatives of 2-phenyl-5-trifluoromethyloxazole-4-carboxarnides. In particular, compound 29 (DGAT-1 enzyme assay, IC(50) = 57 nM; CHO-K1 cell triglyceride formation assay, EC(50) = 0.5 mu M) demonstrated dose dependent inhibition of weight gain in diet induced obese (DIO) rats (0.3, 1, and 3 mg/kg, PO, qd) during a 21-day efficacy study. Furthermore, compound 29 demonstrated improved glucose tolerance determined by an oral glucose tolerance test (OGTT).

  DOI：

  10.1021/jm101580m
• 作为产物：
  描述：

  trans-1,4-Cyclohexanedicarboxylic acid 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.0h， 生成
  参考文献：
  名称：

  Discovery of Orally Active Carboxylic Acid Derivatives of 2-Phenyl-5-trifluoromethyloxazole-4-carboxamide as Potent Diacylglycerol Acyltransferase-1 Inhibitors for the Potential Treatment of Obesity and Diabetes

  摘要：

  Diacylglycerol acyltransferase-1 (DGAT-1) is the enzyme that catalyzes the final and committed step of triglyceride formation, namely, the acylation of diacylglycerol with acyl coenzyme A. DGAT-1 deficient mice demonstrate resistance to weight gain on high fat diet, improved insulin sensitivity, and reduced liver triglyceride content. Inhibition of DGAT-1 thus represents a potential novel approach for the treatment of obesity, dyslipidemia, and metabolic syndrome. In this communication, we report the identification of the lead structure 6 and our lead optimization efforts culminating in the discovery of potent, selective, and orally efficacious carboxylic acid derivatives of 2-phenyl-5-trifluoromethyloxazole-4-carboxarnides. In particular, compound 29 (DGAT-1 enzyme assay, IC(50) = 57 nM; CHO-K1 cell triglyceride formation assay, EC(50) = 0.5 mu M) demonstrated dose dependent inhibition of weight gain in diet induced obese (DIO) rats (0.3, 1, and 3 mg/kg, PO, qd) during a 21-day efficacy study. Furthermore, compound 29 demonstrated improved glucose tolerance determined by an oral glucose tolerance test (OGTT).

  DOI：

  10.1021/jm101580m

文献信息

• Trans-4-[[(5S)-5-[[[3,5-bis(trifluoromethyl)phenyl]methyl](2-methyl-2H-tetrazol-5-yl)amino]-2,3,4,5-tetrahydro-7,9-dimethyl-1H-1-benzazepin-1-yl]methyl]-cyclohexanecarboxylic acid
  申请人：Chen Xinchao

  公开号：US20100331309A1

  公开（公告）日：2010-12-30

  Compounds of a formula entitled, trans-4-[[(5S)-5-[[[3,5-bis(trifluoromethyl)phenyl]methyl](2-methyl-2H-tetrazol-5-yl)amino]-2,3,4,5-tetrahydro-7,9-dimethyl-1H-1-benzazepin- 1 -yl]methyl]-cyclohexanecarboxylic acid, as a free acid or a pharmaceutically acceptable salt thereof; and hydrates and other solvates in crystalline form; pharmaceutical formulations; and methods of use are disclosed.

  本发明涉及一种名为trans-4-[[(5S)-5-[[[3,5-双三氟甲基苯基]甲基](2-甲基-2H-四唑-5-基)氨基]-2,3,4,5-四氢-7,9-二甲基-1H-1-苯并氮杂环-1-基]甲基]-环己烷羧酸的化合物，其为自由酸或其药学上可接受的盐；以及在晶体形式下的水合物和其他溶剂化合物；药物制剂；以及使用方法。
• Trans-4-[[(5S)-5-[[[3,5-bis(trifluoromethyl)phenyl]methyl] (2-methyl-2H-tetrazol-5-yl)amino]-2,3,4,5-tetrahydro-7,9-dimethyl-1H-1-benzazepin-1-yl]methyl]-cyclohexanecarboxylic acid
  申请人：Chen Xinchao

  公开号：US20120058990A1

  公开（公告）日：2012-03-08

  Abstract Compounds of a formula entitled, trans-4-[[(5S)-5-[[[3,5-bis(trifluoromethyl)phenyl]methyl](2-methyl-2H-tetrazol-5-yl)amino]-2,3,4,5-tetrahydro-7,9-dimethyl-1H-1-benzazepin-1-yl]methyl]-cyclohexanecarboxylic acid, as a free acid or a pharmaceutically acceptable salt thereof, hydrate, and hydrate in crystalline form; pharmaceutical formulations; and methods of use are disclosed.

  本发明涉及一种名为trans-4-[[(5S)-5-[[[3,5-双三氟甲基苯基]甲基](2-甲基-2H-四唑-5-基)氨基]-2,3,4,5-四氢-7,9-二甲基-1H-1-苯并氮杂环-1-基]甲基]-环己烷羧酸的化合物，其可以是自由酸或其药学上可接受的盐，水合物以及晶体形式的水合物；药物制剂；以及使用方法。
• TRANS-4-[[(5S)-5-[[[3,5-BIS(TRIFLUOROMETHYL)PHENYL]METHYL](2-METHYL-2H-TETRAZOL-5-YL)AMINO]-2,3,4,5-TETRAHYDRO-7,9-DIMETHYL-1H-1-BENZAZEPIN-1-YL]METHYL]-CYCLOHEXANECARBOXYLIC ACID
  申请人：Eli Lilly and Company

  公开号：EP2448933A1

  公开（公告）日：2012-05-09
• US8299060B2
  申请人：——

  公开号：US8299060B2

  公开（公告）日：2012-10-30
• US8329688B2
  申请人：——

  公开号：US8329688B2

  公开（公告）日：2012-12-11