3α,7α-dihydroxy-6α-ethyl-24-nor-5β-cholan-23-sulphate triethylammonium salt

• 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: 3α,7α-dihydroxy-6α-ethyl-24-nor-5β-cholan-23-sulphate triethylammonium salt
• 英文别名: 3α,7α,23-trihydroxy-6α-ethyl-24-nor-5β-cholan-23-sulphate triethylamine；UPF-987；3α,7α,23-trihydroxy-6α-ethyl-24-nor-5β-cholan-23-sulphate triethyl ammonium salt；N,N-diethylethanamine;[(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]butyl] hydrogen sulfate
• 化学式: C₆H₁₅N*C₂₅H₄₄O₆S
• 分子量: 573.879
• InChiKey: MKCHWQVDJWGIDR-PMWRKVJASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.81
• 重原子数：
  39
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  116
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3α-tetrahydropyranyloxy-6α-ethyl-7-keto-5β-cholan-24-oic acid 在 咪唑 、 盐酸 、 氯磺酸 、 双(乙腈)氯化钯(II) 、 sodium tetrahydroborate 、 水 、 碘 、 lead(IV) tetraacetate 、 silver carbonate 作用下， 以 四氢呋喃 、 四氯化碳 、 二氯甲烷 、 丙酮 为溶剂， 反应 22.5h， 生成 3α,7α-dihydroxy-6α-ethyl-24-nor-5β-cholan-23-sulphate triethylammonium salt
  参考文献：
  名称：

  Treatment of Pulmonary Disease

  摘要：

  本发明涉及使用化合物A的方法，用于治疗、减少风险、预防或缓解肺部疾病或状况的症状，减少或抑制肺部炎症，并促进肺部修复，或其药用盐。

  公开号：

  US20140148428A1

文献信息

• [EN] METHODS OF PROMOTING HEPATIC REGENERATION<br/>[FR] PROCÉDÉS POUR FAVORISER LA RÉGÉNÉRATION HÉPATIQUE
  申请人：INTERCEPT PHARMACEUTICALS INC

  公开号：WO2017053428A1

  公开（公告）日：2017-03-30

  The present invention relates to methods of accelerating, promoting or increasing hepatic regeneration, or increasing liver mass in a subject, by using a compound of formula (A): or a pharmaceutically acceptable salt thereof, and wherein R1, R2, R3, R4, R5, R6, m, and n are as described herein.

  本发明涉及利用化合物(A)或其药学上可接受的盐，在受试者中加速、促进或增加肝再生，或增加肝脏质量的方法，其中R1、R2、R3、R4、R5、R6、m和n如本文所述。
• WO2008/2573
  申请人：——

  公开号：——

  公开（公告）日：——
• Design, Synthesis, and Biological Evaluation of Potent Dual Agonists of Nuclear and Membrane Bile Acid Receptors
  作者：Claudio D’Amore、Francesco Saverio Di Leva、Valentina Sepe、Barbara Renga、Chiara Del Gaudio、Maria Valeria D’Auria、Angela Zampella、Stefano Fiorucci、Vittorio Limongelli

  DOI：10.1021/jm401873d

  日期：2014.2.13

  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.