methyl 6α-ethyl-3α, 7α-dihydroxy-24-nor-5β-cholan-23-oate | 1537866-45-7

• 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 6α-ethyl-3α, 7α-dihydroxy-24-nor-5β-cholan-23-oate
• 英文别名: methyl 3α,7α-dihydroxy-6α-ethyl-24-nor-5β-cholan-23-oate；methyl (3R)-3-[(3R,5S,6R,7R,8S,9S,10S,13R,14S,17R)-6-ethyl-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]butanoate
• CAS: 1537866-45-7
• 化学式: C₂₆H₄₄O₄
• 分子量: 420.633
• InChiKey: SGMYYDZMSFBDFU-ZWECCWDJSA-N

物化性质

• 沸点：
  514.6±25.0 °C(Predicted)
• 密度：
  1.066±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 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 6α-ethyl-3α, 7α-dihydroxy-24-nor-5β-cholan-23-oate 在 2,6-二甲基吡啶 、 盐酸 、 甲醇 、 锂硼氢 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 61.0h， 生成 3α,7α-dihydroxy-6α-ethyl-24-nor-5β-cholan-23-sulphate triethylammonium salt
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Potent Dual Agonists of Nuclear and Membrane Bile Acid Receptors

  摘要：

  Bile acids exert genomic and nongenomic effects by interacting with membrane G-protein-coupled receptors, including the bile acid receptor GP-BAR1, and nuclear receptors, such as the farnesoid X receptor (FXR). These receptors regulate overlapping metabolic functions; thus, GP-BAR1/FXR dual agonists, by enhancing the biological response, represent an innovative strategy for the treatment of enteroendocrine disorders. Here, we report the design, total synthesis, and in vitro/in vivo pharmacological evaluation of a new generation of dual bile acid receptor agonists, with the most potent compound, 19, showing promising pharmacological profiles. We show that compound 19 activates GP-BAR1, FXR, and FXR regulated genes in the liver, increases the intracellular concentration of cAMP, and stimulates the release of the potent insulinotropic hormone GLP-1, resulting in a promising drug candidate for the treatment of metabolic disorders. We also elucidate the binding mode of the most potent dual agonists in the two receptors through a series of computations providing the molecular basis for dual GP-BAR1/FXR agonism.

  DOI：

  10.1021/jm401873d
• 作为产物：
  描述：

  甲醇 、 3α,7α-dihydroxy-6α-ethyl-24-nor-5β-cholan-23-oic acid 在 对甲苯磺酸 作用下， 反应 16.0h， 以120 g的产率得到methyl 6α-ethyl-3α, 7α-dihydroxy-24-nor-5β-cholan-23-oate
  参考文献：
  名称：

  用于代谢性疾病治疗的化合物及其制备方法 和应用

  摘要：

  本发明提供了一种用于代谢性疾病治疗的化合物，具有式(I)或式(Ⅱ)所示结构，或其消旋体，立体异构体，几何异构体，互变异构体，溶剂化物，水合物，代谢产物，药学上可接受的盐或其前药。本发明提供的化合物为FXR和/或TGR5受体激活物，其具有激活FXR和/或TGR5受体活性，可用于制备治疗慢性肝病、代谢性疾病或门脉高压症的药物。

  公开号：

  CN109929005B

文献信息

• TGR5 modulators and methods of use thereof
  申请人：Intercept Pharmaceuticals, Inc.

  公开号：US10800807B2

  公开（公告）日：2020-10-13

  The application relates to compounds of formula A: or a salt, solvate, ester, tautomer, amino acid conjugate, or metabolite thereof. The compounds of formula A are TGR5 modulators useful for the treatment of various diseases, including metabolic disease, inflammatory disease, autoimmune disease, cardiac disease, kidney disease, cancer, and gastrointestinal disease.

  本申请涉及式 A 的化合物： 或其盐、溶解物、酯、同系物、氨基酸共轭物或代谢物。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、自身免疫性疾病、心脏病、肾病、癌症和胃肠道疾病。
• [EN] TGR5 MODULATORS AND METHODS OF USE THEREOF<br/>[FR] MODULATEURS DE TGR5 ET LEURS PROCÉDÉS D'UTILISATION
  申请人：INTERCEPT PHARMACEUTICALS INC

  公开号：WO2016205475A3

  公开（公告）日：2017-02-23
• TGR5 MODULATORS AND METHODS OF USE THEREOF
  申请人：Intercept Pharmaceuticals, Inc.

  公开号：EP3310801B1

  公开（公告）日：2021-04-07
• BILE ACID ANALOGS AS FXR/TGR5 AGONISTS AND METHODS OF USE THEREOF
  申请人：Enanta Pharmaceuticals, Inc.

  公开号：US20160145296A1

  公开（公告）日：2016-05-26

  The present invention relates to compounds of Formula (IA) and Formula (IB), and pharmaceutically acceptable salts thereof, where R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 and m are as defined herein, pharmaceutical compositions comprising these compounds and methods of use of these compounds for treating a TGR5 mediated disease or condition.