methyl 23-methyl-3α,7α-dihydroxy-5β-cholan-24-oate | 1041045-72-0

• 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: methyl 23-methyl-3α,7α-dihydroxy-5β-cholan-24-oate
• 英文别名: methyl 23(R,S)-methyl-3α,7α-dihydroxy-5β-cholan-24-oate；Methyl 23-methyl-3alpha,7alpha-dihydroxy-5beta-cholan-24-oate；methyl (4R)-4-[(3R,5S,7R,8R,9S,10S,13R,14S,17R)-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoate
• CAS: 1041045-72-0
• 化学式: C₂₆H₄₄O₄
• 分子量: 420.633
• InChiKey: MGFFDRHIBJFBHB-SQTJUVEYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.96
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 23-methyl-3α,7α-dihydroxy-5β-cholan-24-oate 在 sodium hydroxide 、 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 16.0h， 以65%的产率得到23(S)-methyl-3α,7α-dihydroxy-5β-cholan-24-oic acid
  参考文献：
  名称：

  TGR5 modulators and methods of use thereof

  摘要：

  本发明涉及式I的化合物：或其药学有效的盐、溶剂化合物、水合物或前药，其中：R1为氢、羟基或卤素；R2为氢或α-羟基；R3为羟基、NH(CH2)mSO3H或NH(CH2)nCO2H；R4为氢、烷基或卤素；R5为未取代或取代的烷基或芳基；R6为氢或R5和R6共同与它们所连接的碳形成大小为3、4、5或6原子的环；m为整数0、1、2、3、4或5，n为整数0、1、2、3、4或5。式I的化合物是TGR5调节剂，可用于治疗各种疾病。

  公开号：

  EP1947108A1
• 作为产物：
  描述：

  methyl 3α,7α-ditetrahydropyran-2'-yloxy-5β-cholan-24-oate 在 盐酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 12.33h， 生成 methyl 23-methyl-3α,7α-dihydroxy-5β-cholan-24-oate
  参考文献：
  名称：

  Nongenomic Actions of Bile Acids. Synthesis and Preliminary Characterization of 23- and 6,23-Alkyl-Substituted Bile Acid Derivatives as Selective Modulators for the G-Protein Coupled Receptor TGR5

  摘要：

  23-Alkyl-substituted and 6,23-alkyl-disubstituted derivatives of chenodeoxvcholic acid are identified as potent and selective agonists of TGR5, a G-protein coupled receptor for bile acids (BAs). In particular. we show that methylation at the C-23(S) position of natural BAs confers a marked selectivity for TGR5 over FXR, while the 6 alpha-alkyl substitution increases the potency at both receptors. The present results allow for the first time a pharmacological differentiation of genomic versus nongenornic effects mediated by BA derivatives.

  DOI：

  10.1021/jm070633p

文献信息

• TGR5 MODULATORS AND METHODS OF USE THEROF
  申请人：Pellicciari Roberto

  公开号：US20100152151A1

  公开（公告）日：2010-06-17

  The invention relates to compounds of Formula A: or a salt, solvate, hydrate, or prodrug thereof. The compounds of Formula A are TGR5 modulators useful for the treatment of various diseases, including metabolic disease, inflammatory disease, liver disease, autoimmune disease, cardiac disease, kidney disease, cancer, and gastrointestinal disease.

  该发明涉及Formula A的化合物：或其盐、溶剂合物、水合物或前药。Formula A的化合物是TGR5调节剂，可用于治疗各种疾病，包括代谢性疾病、炎症性疾病、肝脏疾病、自身免疫疾病、心脏疾病、肾脏疾病、癌症和消化系统疾病。
• TGR5 Modulators and Methods of Use Thereof
  申请人：Pellicciari Roberto

  公开号：US20120115832A1

  公开（公告）日：2012-05-10

  The invention relates to compounds of Formula A: or a salt, solvate, hydrate, or prodrug thereof. The compounds of Formula A are TGR5 modulators useful for the treatment of various diseases, including metabolic disease, inflammatory disease, liver disease, autoimmune disease, cardiac disease, kidney disease, cancer, and gastrointestinal disease.

  本发明涉及A式化合物：或其盐、溶剂合物、水合物或前药。A式化合物是TGR5调节剂，可用于治疗各种疾病，包括代谢性疾病、炎症性疾病、肝脏疾病、自身免疫性疾病、心脏疾病、肾脏疾病、癌症和胃肠疾病。
• 23-substituted bile acids as TGR5 modulators and methods of use thereof
  申请人：Pellicciari Roberto

  公开号：US08410083B2

  公开（公告）日：2013-04-02

  The invention relates to compounds of Formula A: (A) or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof. The compounds of Formula A are TGR5 modulators useful for the treatment of various diseases, including obesity, insulin sensitivity, inflammation, cholestasis, and bile desaturation.

  该发明涉及化合物A的公式：（A）或其药学上可接受的盐，溶剂化合物，水合物或前药。公式A的化合物是TGR5调节剂，可用于治疗各种疾病，包括肥胖症，胰岛素敏感性，炎症，胆汁淤积和胆汁脱饱和。
• 23-Substituted Bile Acids as TGR5 Modulators and Methods of Use Thereof
  申请人：Pellicciari Roberto

  公开号：US20110003782A1

  公开（公告）日：2011-01-06

  The invention relates to compounds of Formula A: (A) or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof. The compounds of Formula A are TGR5 modulators useful for the treatment of various diseases, including obesity, insulin sensitivity, inflammation, cholestasis, and bile desaturation.

  本发明涉及A式化合物：（A），或其药学上可接受的盐、溶剂化合物、水合物或前药。A式化合物是TGR5调节剂，可用于治疗各种疾病，包括肥胖症、胰岛素敏感性、炎症、胆汁淤积和胆汁脱饱和。
• TGR5 modulators and method of use thereof
  申请人：Intercept Pharmaceuticals, Inc.

  公开号：EP2698375A2

  公开（公告）日：2014-02-19

  The invention relates to compounds of Formula A: (A) or a salt, solvate, hydrate, or prodrug thereof. The compounds of Formula A are TGR5 modulators useful for the treatment of various diseases, including metabolic disease, inflammatory disease, liver disease, autoimmune disease, cardiac disease, kidney disease, cancer and gastrointestinal disease.

  本发明涉及式 A 的化合物：(A)或其盐、溶液剂、水合物或原药。式 A 的化合物是 TGR5 调节剂，可用于治疗各种疾病，包括代谢性疾病、炎症性疾病、肝病、自身免疫性疾病、心脏病、肾病、癌症和胃肠道疾病。