methyl 3α-hydroxy-7-keto-6α-allyl-5β-cholan-24-oate | 756852-21-8

• 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-hydroxy-7-keto-6α-allyl-5β-cholan-24-oate
• 英文别名: methyl (4R)-4-[(3R,5S,6R,8S,9S,10S,13R,14S,17R)-3-hydroxy-10,13-dimethyl-7-oxo-6-prop-2-enyl-1,2,3,4,5,6,8,9,11,12,14,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]pentanoate
• CAS: 756852-21-8
• 化学式: C₂₈H₄₄O₄
• 分子量: 444.655
• InChiKey: WSNIBQAUGPHGMH-GAKWKJAJSA-N

物化性质

• 沸点：
  530.7±30.0 °C(Predicted)
• 密度：
  1.053±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 3α-hydroxy-7-keto-6α-allyl-5β-cholan-24-oate 在 臭氧 、 sodium tetrahydroborate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 4.0h， 以31%的产率得到methyl 3α,7α-dihydroxy-6α-(2-hydroxyethyl)-5β-cholan-24-oate
  参考文献：
  名称：

  Bile Acid Derivatives as Ligands of the Farnesoid X Receptor. Synthesis, Evaluation, and Structure−Activity Relationship of a Series of Body and Side Chain Modified Analogues of Chenodeoxycholic Acid

  摘要：

  The farnesoid X receptor (FXR) is activated by endogenous bile acids (BAs) and plays a variety of physiological roles related to modulation of gene transcription. In particular, FXR positively regulates the cholesterol catabolism while feedback inhibits the BA synthesis by repressing the expression of the CYP7A and CYP8B genes. We have previously shown that 6alpha-ethyl-CDCA (6ECDCA) is a potent and selective FXR agonist. In this paper we report an extensive structure-activity relationship for a series of synthetic bile acids. Our results indicate that the 6alpha position plays a fundamental role in determining affinity and that the side chain of BA is amenable to a variety of chemical modification. Although none of the new derivatives is more potent than 6ECDCA, we show here that a wide variability in efficacy, from full agonists to partial antagonists, can be obtained.

  DOI：

  10.1021/jm049904b
• 作为产物：
  描述：

  3Α-羟基-7-氧代-5Β-胆烷酸 在 对甲苯磺酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 六甲基磷酰三胺 、 正己烷 为溶剂， 反应 12.58h， 生成 methyl 3α-hydroxy-7-keto-6α-allyl-5β-cholan-24-oate
  参考文献：
  名称：

  Bile Acid Derivatives as Ligands of the Farnesoid X Receptor. Synthesis, Evaluation, and Structure−Activity Relationship of a Series of Body and Side Chain Modified Analogues of Chenodeoxycholic Acid

  摘要：

  The farnesoid X receptor (FXR) is activated by endogenous bile acids (BAs) and plays a variety of physiological roles related to modulation of gene transcription. In particular, FXR positively regulates the cholesterol catabolism while feedback inhibits the BA synthesis by repressing the expression of the CYP7A and CYP8B genes. We have previously shown that 6alpha-ethyl-CDCA (6ECDCA) is a potent and selective FXR agonist. In this paper we report an extensive structure-activity relationship for a series of synthetic bile acids. Our results indicate that the 6alpha position plays a fundamental role in determining affinity and that the side chain of BA is amenable to a variety of chemical modification. Although none of the new derivatives is more potent than 6ECDCA, we show here that a wide variability in efficacy, from full agonists to partial antagonists, can be obtained.

  DOI：

  10.1021/jm049904b