methyl 3α,7α-ditetrahydropyran-2'-yloxy-5β-cholan-24-oate | 91788-59-9

• 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 3α,7α-ditetrahydropyran-2'-yloxy-5β-cholan-24-oate
• 英文别名: methyl 3α,7α-di(tetrahydropyranyloxy)-5β-cholan-24-oate；methyl 3α,7α-ditetrahydropyranyloxy-5β-cholan-24-oate；methyl 3a,7a-ditetrahydropyranyloxy-5β-cholan-24-oate；Methyl 3alpha,7alpha-ditetrahydropyranyloxy-5beta-cholan-24-oate；methyl (4R)-4-[(3R,5S,7R,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-3,7-bis(oxan-2-yloxy)-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoate
• CAS: 91788-59-9
• 化学式: C₃₅H₅₈O₆
• 分子量: 574.842
• InChiKey: LEYXYQDCDPUJJO-ORRLORIESA-N

物化性质

• 沸点：
  627.1±55.0 °C(Predicted)
• 密度：
  1.10±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  8
• 重原子数：
  41
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.97
• 拓扑面积：
  63.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  鹅去氧胆酸 在 硫酸 、 对甲苯磺酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 12.5h， 生成 methyl 3α,7α-ditetrahydropyran-2'-yloxy-5β-cholan-24-oate
  参考文献：
  名称：

  BILE ACID ANALOG TGR5 AGONISTS

  摘要：

  本文提供了胆酸类似物和衍生物，合成胆酸类似物和衍生物的方法以及它们在治疗糖尿病和肝病中的应用。

  公开号：

  US20140206657A1

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：Intercept Pharmaceuticals, Inc.

  公开号：EP1947108A1

  公开（公告）日：2008-07-23

  The invention relates to compounds of Formula I: or a pharmaceutically effective salt, solvate, hydrate, or prodrug thereof, wherein: R1 is hydrogen, hydroxy, or halogen; R2 is hydrogen or α-hydroxy; R3 is hydroxy, NH(CH2)mSO3H, or NH(CH2)nCO2H; R4 is hydrogen, alkyl, or halogen; R5 is unsubstituted or substituted alkyl, or aryl; R6 is hydrogen or R5 and R6 taken together with the carbons to which they are attached form a ring of size 3, 4, 5, or 6 atoms; m is an integer 0, 1, 2, 3, 4, or 5, and n is an integer 0, 1, 2, 3, 4, or 5. The compounds of Formula I are TGR5 modulators useful for the treatment of various diseases.

  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( )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。
• 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。