(S)-((1S,4bR,8aS,10aS)-4b,8,8,10a-tetramethyl-7-oxo-1,2,3,4b,5,6,7,8,8a,9,10,10a-dodecahydrophenanthren-1-yl) 3,3,3-trifluoro-2-methoxy-2-phenylpropanoate | 1273015-77-2

• 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: (S)-((1S,4bR,8aS,10aS)-4b,8,8,10a-tetramethyl-7-oxo-1,2,3,4b,5,6,7,8,8a,9,10,10a-dodecahydrophenanthren-1-yl) 3,3,3-trifluoro-2-methoxy-2-phenylpropanoate
• CAS: 1273015-77-2
• 化学式: C₂₈H₃₅F₃O₄
• 分子量: 492.579
• InChiKey: PSSOGPAJGVBHII-UMWSZVTCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.53
• 重原子数：
  35.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  52.6
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为产物：
  描述：

  (4aSR,8RS,8aRS)-8-hydroxy-1,4a,8a-trimethyl-4,4a,6,7,8,8a,9,10-octahydrophenanthren-2(3H)-one 在 吡啶 、 lithium 作用下， 以 四氢呋喃 、 四氯化碳 、 氨 为溶剂， 反应 29.0h， 生成 (S)-((1S,4bR,8aS,10aS)-4b,8,8,10a-tetramethyl-7-oxo-1,2,3,4b,5,6,7,8,8a,9,10,10a-dodecahydrophenanthren-1-yl) 3,3,3-trifluoro-2-methoxy-2-phenylpropanoate
  参考文献：
  名称：

  Tricyclic Compounds Containing Nonenolizable Cyano Enones. A Novel Class of Highly Potent Anti-Inflammatory and Cytoprotective Agents

  摘要：

  Forty-four novel tricycles containing nonenolizable cyano enones (TCEs) were designed and synthesized on the basis of a semisynthetic pentacyclic triterpenoid, bardoxolone methyl, which is currently being developed in phase II clinical trials for the treatment of severe chronic kidney disease in diabetic patients. Most of the TCEs having two different kinds of nonenolizable cyano enones in rings A and C are highly potent suppressors of induction of inducible nitric oxide synthase stimulated with interferon-gamma and are highly potent inducers of the cytoprotective enzymes heme oxygenase-1 and NAD(P)H:quinone oxidoreductase-1. Among these compounds, (+/-)-(4bS,8aR,10aS)-10a-ethynyl-4b,8,8-trimethyl-3,7-dioxo-3,4b,7,8,8a,9,10,10a-octahydrophenanthrene-2,6-dicarbonitrile ((+/-)-31) is the most potent in these bioassays in our pool of drug candidates including semisynthetic triterpenoids and synthetic tricycles. These facts strongly suggest that an essential factor for potency is not a triterpenoid skeleton but the cyano enone functionality. Notably, TCE 31 reduces hepatic tumorigenesis induced with aflatoxin in rats. Further preclinical studies and detailed mechanism studies on 31 are in progress.

  DOI：

  10.1021/jm101445p