(2R,3R,4aR,10aR)-4a-ethyl-3-methyl-2-(prop-1-ynyl)-1,2,3,4,4a,9,10,10a-octahydrophenanthrene-2,3,7-triol

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 英文名称: (2R,3R,4aR,10aR)-4a-ethyl-3-methyl-2-(prop-1-ynyl)-1,2,3,4,4a,9,10,10a-octahydrophenanthrene-2,3,7-triol
• 英文别名: (2R,3R,4aR,10aR)-4a-ethyl-3-methyl-2-prop-1-ynyl-1,2,3,4,4a,9,10,10a-octahydro-phenanthrene-2,3,7-triol；(2R,3R,4aR,10aR)-4a-ethyl-3-methyl-2-prop-1-ynyl-4,9,10,10a-tetrahydro-1H-phenanthrene-2,3,7-triol
• 化学式: C₂₀H₂₆O₃
• 分子量: 314.425
• InChiKey: OHSVDENSKJRCTF-XLNTUCKNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  60.7
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  (3E,4aR,10aR)-3-benzylidene-4a-ethyl-7-hydroxy-3,4,4a,9,10,10a-hexahydro-1H-phenanthren-2-one 在 盐酸 、 水 、 对甲苯磺酸 、 臭氧 、 lithium chloride 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 47.0h， 生成 (2R,3R,4aR,10aR)-4a-ethyl-3-methyl-2-(prop-1-ynyl)-1,2,3,4,4a,9,10,10a-octahydrophenanthrene-2,3,7-triol 、 (2S,3R,4aR,10aR)-4a-ethyl-3-methyl-2-(prop-1-ynyl)-1,2,3,4,4a,9,10,10a-octahydrophenanthrene-2,3,7-triol
  参考文献：
  名称：

  2-Aryl-3-methyloctahydrophenanthrene-2,3,7-triols as Potent Dissociated Glucocorticoid Receptor Agonists

  摘要：

  A significant improvement in agonist activity of the previously described 2-aryloctahydrophenanthrene-2,3,7-triol series of dissociated glucocorticoid receptor agonists (DAGRs) was achieved by modifying the substitution at C3 from (S)-3-hydroxy to (R)-3-hydroxy-3-methyl. The IC50 of the prototype 13 in the efficacy assay measuring repression of IL-1 induced MMP-13 expression was 3.5 nM, exhibiting 87% of the maximal effect of dexamethasone (DEX). It displayed a dissociated profile by exhibiting 42% of the maximal effect of DEX in a mouse mammary tumor virus (MMTV) luciferase reporter transactivation assay. Compound 13 and analogues containing heterocyclic replacements for the C2 phenyl and modified B rings showed high repression of TNF alpha production in human whole blood, with IC50 values (43-167 nM) approaching the level of DEX (21 nM). On the basis of X-ray structures and force field calculations, the overall potency of this series was attributed to a favorable conformation of the C2 alpha phenyl, induced by the neighboring C3 alpha methyl.

  DOI：

  10.1021/jm501601b

文献信息

• Modulators of the glucocorticoid receptor
  申请人：Pfizer Inc.

  公开号：US20040138262A1

  公开（公告）日：2004-07-15

  The present invention provides compounds of the formula 1 wherein A is of the formula 2 and X, Y, n, R 1 -R 25 are as described in the specification which are modulators of the glucocorticoid receptor and are thus useful for the treatment of animals requiring glucocorticoid receptor agonist therapy. Glucocorticoid receptor modulators are useful in the treatment of certain inflammatory conditions.

  本发明提供了一些化合物，其化学式为1，其中A的化学式为2，X、Y、n、R1-R25如说明书所述，这些化合物是糖皮质激素受体调节剂，因此对需要糖皮质激素受体激动剂治疗的动物有用。糖皮质激素受体调节剂在治疗某些炎症病症方面是有用的。
• US7138406B2
  申请人：——

  公开号：US7138406B2

  公开（公告）日：2006-11-21
• US7553877B2
  申请人：——

  公开号：US7553877B2

  公开（公告）日：2009-06-30
• 2-Aryl-3-methyloctahydrophenanthrene-2,3,7-triols as Potent Dissociated Glucocorticoid Receptor Agonists
  作者：Yves A. Chantigny、John C. Murray、Edward F. Kleinman、Ralph P. Robinson、Michael A. Plotkin、Matthew R. Reese、Leonard Buckbinder、Patricia A. McNiff、Michele L. Millham、Jean F. Schaefer、Yuriy A. Abramov、Jon Bordner

  DOI：10.1021/jm501601b

  日期：2015.3.26

  A significant improvement in agonist activity of the previously described 2-aryloctahydrophenanthrene-2,3,7-triol series of dissociated glucocorticoid receptor agonists (DAGRs) was achieved by modifying the substitution at C3 from (S)-3-hydroxy to (R)-3-hydroxy-3-methyl. The IC50 of the prototype 13 in the efficacy assay measuring repression of IL-1 induced MMP-13 expression was 3.5 nM, exhibiting 87% of the maximal effect of dexamethasone (DEX). It displayed a dissociated profile by exhibiting 42% of the maximal effect of DEX in a mouse mammary tumor virus (MMTV) luciferase reporter transactivation assay. Compound 13 and analogues containing heterocyclic replacements for the C2 phenyl and modified B rings showed high repression of TNF alpha production in human whole blood, with IC50 values (43-167 nM) approaching the level of DEX (21 nM). On the basis of X-ray structures and force field calculations, the overall potency of this series was attributed to a favorable conformation of the C2 alpha phenyl, induced by the neighboring C3 alpha methyl.