(4R)-4-[(1R,2S,5R,6R,9S,10S)-1,5,14,14,17-pentamethyl-16,18-diazapentacyclo[11.8.0.02,10.05,9.015,20]henicosa-12,15,17,19-tetraen-6-yl]pentanoic acid | 1414953-81-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: (4R)-4-[(1R,2S,5R,6R,9S,10S)-1,5,14,14,17-pentamethyl-16,18-diazapentacyclo[11.8.0.02,10.05,9.015,20]henicosa-12,15,17,19-tetraen-6-yl]pentanoic acid
• CAS: 1414953-81-3
• 化学式: C₂₉H₄₂N₂O₂
• 分子量: 450.665
• InChiKey: RZYKYTXZEFMVOT-BPJZVGOOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  63.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  choladiene-1,4 one-3 oate-24 de methyle 在 potassium tert-butylate 、 水 、 sodium methylate 、 lithium hydroxide 作用下， 以 乙醇 为溶剂， 生成 (4R)-4-[(1R,2S,5R,6R,9S,10S)-1,5,14,14,17-pentamethyl-16,18-diazapentacyclo[11.8.0.02,10.05,9.015,20]henicosa-12,15,17,19-tetraen-6-yl]pentanoic acid
  参考文献：
  名称：

  Synthesis and biological evaluation of 4,4-dimethyl lithocholic acid derivatives as novel inhibitors of protein tyrosine phosphatase 1B

  摘要：

  Protein tyrosine phosphatase 1B (PTP1B) is a major negative regulator of both insulin and leptin signals. For years, inhibiting of PTP1B has been considered to be a potential therapeutics for treating Type 2 diabetes and obesity. Recently, we recognized lithocholic acid (LCA) as a natural inhibitor against PTP1B (IC50 = 12.74 mu M) by a vertical screen for the first time. Further SAR research was carried out by synthesizing and evaluating a series of compounds bearing two methyls at C-4 position and a fused heterocycle to ring A. Among them, compound 14b achieved a PTP1B inhibitory activity about eightfold than LCA and a 14-fold selectivity over the homogenous enzyme TCPTP. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.09.040

文献信息

• Synthesis and biological evaluation of 4,4-dimethyl lithocholic acid derivatives as novel inhibitors of protein tyrosine phosphatase 1B
  作者：Hai-Bing He、Li-Xin Gao、Qi-Feng Deng、Wei-Ping Ma、Chun-Lan Tang、Wen-Wei Qiu、Jie Tang、Jing-Ya Li、Jia Li、Fan Yang

  DOI：10.1016/j.bmcl.2012.09.040

  日期：2012.12

  Protein tyrosine phosphatase 1B (PTP1B) is a major negative regulator of both insulin and leptin signals. For years, inhibiting of PTP1B has been considered to be a potential therapeutics for treating Type 2 diabetes and obesity. Recently, we recognized lithocholic acid (LCA) as a natural inhibitor against PTP1B (IC50 = 12.74 mu M) by a vertical screen for the first time. Further SAR research was carried out by synthesizing and evaluating a series of compounds bearing two methyls at C-4 position and a fused heterocycle to ring A. Among them, compound 14b achieved a PTP1B inhibitory activity about eightfold than LCA and a 14-fold selectivity over the homogenous enzyme TCPTP. (C) 2012 Elsevier Ltd. All rights reserved.