6ALPHA-乙基-23(S)-甲基胆酸 | 1199796-29-6

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 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
• 中文名称: 6ALPHA-乙基-23(S)-甲基胆酸
• 英文名称: (S)-EMCA
• 英文别名: 6α-ethyl-23(S)-methyl-3α,7α,12α-trihydroxy-5β-cholan-24-oic acid；3α,7α,12α-trihydroxy-6α-ethyl-23-methyl-5β-cholan-24-oic acid；6α-ethyl-23(S)-methyl-cholic acid；6α-ethyl-23(S)-methylcholic acid；6-ethyl-23(S)-methylcholic acid；INT‐777；Int-777；(2S,4R)-4-[(3R,5S,6R,7R,8R,9S,10S,12S,13R,14S,17R)-6-ethyl-3,7,12-trihydroxy-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-methylpentanoic acid
• CAS: 1199796-29-6
• 化学式: C₂₇H₄₆O₅
• 分子量: 450.659
• InChiKey: NPBCMXATLRCCLF-IRRLEISYSA-N

物化性质

• 熔点：
  150-152℃
• 沸点：
  602.8±55.0 °C(Predicted)
• 密度：
  1.128±0.06 g/cm3(Predicted)
• 溶解度：
  DMF:30.0(最大浓度 mg/mL);66.57(最大浓度 mM)DMF:PBS (pH 7.2) (1:1):0.5(最大浓度 mg/mL);1.11(最大浓度. mM)DMSO:25.5(最大浓度 mg/mL);56.58(最大浓度 mM)乙醇:37.5(最大浓度 mg/mL);83.21(最大浓度 mM)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  32
• 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：
  98
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  methyl (4R)-4-[(3R,5S,6R,7R,8R,9S,10S,12S,13R,14S,17R)-6-ethyl-3,7,12-trihydroxy-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 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以53%的产率得到6ALPHA-乙基-23(S)-甲基胆酸
  参考文献：
  名称：

  Discovery of 6α-Ethyl-23(S)-methylcholic Acid (S-EMCA, INT-777) as a Potent and Selective Agonist for the TGR5 Receptor, a Novel Target for Diabesity

  摘要：

  In the framework of the design and development of TGR5 agonists, we reported that the introduction of a C-23(S)methyl group in the side chain of bile acids such as chenodeoxycholic acid (CDCA) and 6-ethylchenodeoxycholic acid (6-ECDCA, INT-747) affords selectivity for TGR5. Herein we report further lead optimization efforts that have led to the discovery of 6 alpha-ethyl-23(S)-methylcholic acid (S-EMCA. INT-777)as a novel Potent and selective TGR5 agonist with remarkable in vivo activity.

  DOI：

  10.1021/jm901390p

文献信息

• BILE ACID RECYCLING INHIBITORS FOR TREATMENT OF GASTROINTESTINAL INFECTIONS
  申请人：Lumena Pharmaceuticals, Inc.

  公开号：US20150119345A1

  公开（公告）日：2015-04-30

  Provided herein are methods for treating or preventing gastrointestinal and/or liver infections utilizing bile acid transport inhibitors and/or enteroendocrine peptide enhancing agents and/or FXR agonists. Also provided herein are methods for increasing the levels of an enteroendocrine peptide or hormone in an individual suffering from a gastrointestinal infection or liver infection utilizing bile acid transport inhibitors and/or enteroendocrine peptide enhancing agents and/or FXR agonists.

  本文提供了利用胆汁酸转运抑制剂和/或肠内分泌肽增强剂和/或FXR激动剂治疗或预防胃肠和/或肝感染的方法。本文还提供了利用胆汁酸转运抑制剂和/或肠内分泌肽增强剂和/或FXR激动剂增加患有胃肠感染或肝感染的个体体内肠内分泌肽或激素水平的方法。
• Benzothiazepine compounds and their use as bile acid modulators
  申请人：Albireo AB

  公开号：US11014898B1

  公开（公告）日：2021-05-25

  The invention relates to 1,5-benzothiazepine derivatives of formula (I). These compounds are bile acid modulators having apical sodium-dependent bile acid transporter (ASBT) and/or liver bile acid transport (LBAT) inhibitory activity. The invention also relates to pharmaceutical compositions comprising these compounds and to the use of these compounds in the treatment of cardiovascular diseases, fatty acid metabolism and glucose utilization disorders, gastrointestinal diseases and liver diseases.

  这项发明涉及式(I)的1,5-苯并噻吩衍生物。这些化合物是胆酸调节剂，具有顶端钠依赖性胆酸转运蛋白（ASBT）和/或肝胆酸转运（LBAT）的抑制活性。该发明还涉及包含这些化合物的药物组合物，以及利用这些化合物治疗心血管疾病、脂肪酸代谢和葡萄糖利用障碍、胃肠道疾病和肝脏疾病的用途。
• 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。
• BENZOTHIA(DI)AZEPINE COMPOUNDS AND THEIR USE AS BILE ACID MODULATORS
  申请人：Albireo AB

  公开号：US20210171482A1

  公开（公告）日：2021-06-10

  The invention relates to 1,5-benzothiazepine and 1,2,5-benzothiadiazepine derivatives of formula (I). These compounds are bile acid modulators having apical sodium-dependent bile acid transporter (ASBT) and/or liver bile acid transport (LBAT) inhibitory activity. The invention also relates to pharmaceutical compositions comprising these compounds and to the use of these compounds in the treatment of cardiovascular diseases, fatty acid metabolism and glucose utilization disorders, gastrointestinal diseases and liver diseases.

  这项发明涉及式(I)的1,5-苯并噻二嗪和1,2,5-苯并噻二氮杂二环己烷衍生物。这些化合物是胆酸调节剂，具有顶端钠依赖性胆酸转运蛋白（ASBT）和/或肝胆酸转运（LBAT）的抑制活性。该发明还涉及包含这些化合物的药物组合物，以及将这些化合物用于治疗心血管疾病、脂肪酸代谢和葡萄糖利用障碍、胃肠道疾病和肝脏疾病。
• [EN] FARNESOID X RECEPTOR MODULATORS<br/>[FR] MODULATEURS DU RÉCEPTEUR FARNÉSOÏDE X
  申请人：INTERCEPT PHARMACEUTICALS INC

  公开号：WO2017062763A1

  公开（公告）日：2017-04-13

  The present application provides a compound of formula I: or a pharmaceutically acceptable salt, solvate, or amino acid conjugate thereof, as described herein. The present invention relates generally to FXR modulators and to methods of making and using said compounds.

  本申请提供了一种化合物，其化学式为I：或其药用可接受的盐、溶剂化合物或氨基酸结合物，如本文所述。本发明一般涉及FXR调节剂以及制备和使用所述化合物的方法。