(3′E,4a′R,10a′R)-3′-benzylidene-4a′-ethyl-3′,4′,4a′,9′,10′,10a′-hexahydro-1′H-spiro[[1,3]dioxolane-2,2′-phenanthrene]-7′-yl 4-nitrobenzoate | 645397-05-3

• 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: (3′E,4a′R,10a′R)-3′-benzylidene-4a′-ethyl-3′,4′,4a′,9′,10′,10a′-hexahydro-1′H-spiro[[1,3]dioxolane-2,2′-phenanthrene]-7′-yl 4-nitrobenzoate
• 英文别名: (4bR,6E,8aR)-4-nitro-benzoic acid 6-benzylidene-4b-ethyl-7-oxo-4b,5,6,7,8,8a,9,10-octahydro-1H-phenanthren-2-yl ester ethylene ketal；[(4'bR,6'E,8'aR)-6'-benzylidene-4'b-ethylspiro[1,3-dioxolane-2,7'-8,8a,9,10-tetrahydro-5H-phenanthrene]-2'-yl] 4-nitrobenzoate
• CAS: 645397-05-3
• 化学式: C₃₂H₃₁NO₆
• 分子量: 525.601
• InChiKey: CJXDUCCPVIOONR-CSKDKGCSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  39
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  90.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (3′E,4a′R,10a′R)-3′-benzylidene-4a′-ethyl-3′,4′,4a′,9′,10′,10a′-hexahydro-1′H-spiro[[1,3]dioxolane-2,2′-phenanthrene]-7′-yl 4-nitrobenzoate 在 盐酸 、 水 、 臭氧 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 、 水 为溶剂， 反应 20.5h， 生成 (3R,4aR,10aR)-4a-ethyl-3,7-dihydroxy-3-methyl-3,4,4a,9,10,10a-hexahydrophenanthren-2(1H)-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 对甲苯磺酸 作用下， 以 甲苯 为溶剂， 反应 13.5h， 生成 (3′E,4a′R,10a′R)-3′-benzylidene-4a′-ethyl-3′,4′,4a′,9′,10′,10a′-hexahydro-1′H-spiro[[1,3]dioxolane-2,2′-phenanthrene]-7′-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

• 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.