(4bR,7S,8aR,E)-6-benzylidene-4b-ethyl-7-hydroxy-7-(pyridin-2-yl)-4b,5,6,7,8,8a,9,10-octahydrophenanthren-2-yl 4-nitrobenzoate | 645397-11-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (4bR,7S,8aR,E)-6-benzylidene-4b-ethyl-7-hydroxy-7-(pyridin-2-yl)-4b,5,6,7,8,8a,9,10-octahydrophenanthren-2-yl 4-nitrobenzoate
• 英文别名: 4-nitrobenzoic acid, (4bR,6E,7S,8aR)-6-benzylidene-4b-ethyl-7-hydroxy-7-pyridin-2-yl-4b,5,6,7,8,8a,9,10-octahydro-phenanthren-2-yl ester；[(4bR,6E,7S,8aR)-6-benzylidene-4b-ethyl-7-hydroxy-7-pyridin-2-yl-8,8a,9,10-tetrahydro-5H-phenanthren-2-yl] 4-nitrobenzoate
• CAS: 645397-11-1
• 化学式: C₃₅H₃₂N₂O₅
• 分子量: 560.649
• InChiKey: HJNAHZYRAKPMAW-QZMVAMHSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  42
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (4bR,7S,8aR,E)-6-benzylidene-4b-ethyl-7-hydroxy-7-(pyridin-2-yl)-4b,5,6,7,8,8a,9,10-octahydrophenanthren-2-yl 4-nitrobenzoate 在 盐酸 、 水 、 臭氧 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 生成 (2R,4aR,10aR)-4a-ethyl-2,7-dihydroxy-2-(pyridin-2-yl)-1,4,4a,9,10,10a-hexahydrophenanthren-3(2H)-one
  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
• 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 咪唑 、 正丁基锂 、 四丁基氟化铵 、 sodium hydroxide 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 水 、 丙酮 为溶剂， 反应 11.0h， 生成 (4bR,7S,8aR,E)-6-benzylidene-4b-ethyl-7-hydroxy-7-(pyridin-2-yl)-4b,5,6,7,8,8a,9,10-octahydrophenanthren-2-yl 4-nitrobenzoate
  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

• [EN] MODULATORS OF THE GLUCOCORTICOID RECEPTOR<br/>[FR] MODULATEURS DU RECEPTEUR GLUCOCORTICOIDE
  申请人：PFIZER PROD INC

  公开号：WO2004005229A1

  公开（公告）日：2004-01-15

  The present invention provides compounds of the formula wherein A is of the formula and X, Y, n, R1-R25 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 ágonist.therapy. Glucocorticoid-receptor modulators are useful in the treatment of certain inflammatory conditions.

  本发明提供了以下式中A为该式，X、Y、n、R1-R25如说明书中所述的化合物，这些化合物是糖皮质激素受体的调节剂，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性疾病中是有用的。