1,1-ethylenedioxy-3-[(E)-3-hydroxy-3-methyl-7-phenyl-1-hepten-1-yl]cyclohexane | 257866-63-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1,1-ethylenedioxy-3-[(E)-3-hydroxy-3-methyl-7-phenyl-1-hepten-1-yl]cyclohexane
• 英文别名: (E)-1-(1,4-dioxaspiro[4.5]decan-7-yl)-3-methyl-7-phenylhept-1-en-3-ol
• CAS: 257866-63-0
• 化学式: C₂₂H₃₂O₃
• 分子量: 344.494
• InChiKey: RPOIMHRXZWVAHW-NTCAYCPXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  38.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,1-ethylenedioxy-3-[(E)-3-hydroxy-3-methyl-7-phenyl-1-hepten-1-yl]cyclohexane 在 正丁基锂 、 4-甲基苯磺酸吡啶 、 二异丙胺 作用下， 以 四氢呋喃 、 正己烷 、 水 、 丙酮 为溶剂， 反应 50.0h， 生成 (1S*,3S*)-1-hydroxy-3-[(E)-3-hydroxy-3-methyl-7-phenyl-1-hepten-1-yl]-1-cyclohexane-1-N,N-dimethyl-acetamide
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of New 1,3-Disubstituted Cyclohexanes as Structurally Rigid Leukotriene B₄ Receptor Antagonists

  摘要：

  A series of 1-hydroxy-3-[3-hydroxy-7-phenyl-1-hepten-1-yl] cyclohexane acetic acid derivatives was designed based on postulated active conformation of leukotriene B-4 (LTB4) and evaluated as human cell surface LTB4 receptor (BLTR) antagonists. Binding was determined through [H-3]LTB4 displacement from human neutrophils and receptor antagonistic assays by in vitro measurements of inhibition of leukocyte chemotaxis induced by LTB4. On the basis of these assays, a structure-affinity relationship was investigated. Optimization of the acid chain length and omega-substitution of a phenyl group on the lipophilic tail were shown to be critical for binding activity. These modifications led to the discovery of compounds with submicromolar potency and selective BLTR antagonism. The most potent compound 3b alpha (IC50 = 250 nM) was found to significantly inhibit oedema formation in a topical model of phorbolester-induced inflammation. Substantial improvement of in vitro potency was achieved by modification of the carboxylic acid function leading to the identification of the N,N-dimethylamide series. Compound 5b alpha, free of agonist activity, displayed higher potency in receptor binding with an IC50 of 40 nM. These results support the hypothesis that the spatial relationship between the carboxylic acid and allylic hydroxyl functions is crucial for high binding affinity with BLTR.

  DOI：

  10.1021/jm9910573
• 作为产物：
  描述：

  methyl 1,4-dioxaspiro[4.5]decane-7-carboxylate 在 sodium hydride 、 二异丁基氢化铝 作用下， 以 乙醚 、 甲苯 为溶剂， 反应 17.5h， 生成 1,1-ethylenedioxy-3-[(E)-3-hydroxy-3-methyl-7-phenyl-1-hepten-1-yl]cyclohexane
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of New 1,3-Disubstituted Cyclohexanes as Structurally Rigid Leukotriene B₄ Receptor Antagonists

  摘要：

  A series of 1-hydroxy-3-[3-hydroxy-7-phenyl-1-hepten-1-yl] cyclohexane acetic acid derivatives was designed based on postulated active conformation of leukotriene B-4 (LTB4) and evaluated as human cell surface LTB4 receptor (BLTR) antagonists. Binding was determined through [H-3]LTB4 displacement from human neutrophils and receptor antagonistic assays by in vitro measurements of inhibition of leukocyte chemotaxis induced by LTB4. On the basis of these assays, a structure-affinity relationship was investigated. Optimization of the acid chain length and omega-substitution of a phenyl group on the lipophilic tail were shown to be critical for binding activity. These modifications led to the discovery of compounds with submicromolar potency and selective BLTR antagonism. The most potent compound 3b alpha (IC50 = 250 nM) was found to significantly inhibit oedema formation in a topical model of phorbolester-induced inflammation. Substantial improvement of in vitro potency was achieved by modification of the carboxylic acid function leading to the identification of the N,N-dimethylamide series. Compound 5b alpha, free of agonist activity, displayed higher potency in receptor binding with an IC50 of 40 nM. These results support the hypothesis that the spatial relationship between the carboxylic acid and allylic hydroxyl functions is crucial for high binding affinity with BLTR.

  DOI：

  10.1021/jm9910573

文献信息

• Synthesis and Structure−Activity Relationships of New 1,3-Disubstituted Cyclohexanes as Structurally Rigid Leukotriene B₄ Receptor Antagonists
  作者：Jean-Marc Poudrel、Pierre Hullot、Jean-Pierre Vidal、Jean-Pierre Girard、Jean-Claude Rossi、Agnès Muller、Claude Bonne、Vladimir Bezuglov、Igor Serkov、Pierre Renard、Bruno Pfeiffer

  DOI：10.1021/jm9910573

  日期：1999.12.1

  A series of 1-hydroxy-3-[3-hydroxy-7-phenyl-1-hepten-1-yl] cyclohexane acetic acid derivatives was designed based on postulated active conformation of leukotriene B-4 (LTB4) and evaluated as human cell surface LTB4 receptor (BLTR) antagonists. Binding was determined through [H-3]LTB4 displacement from human neutrophils and receptor antagonistic assays by in vitro measurements of inhibition of leukocyte chemotaxis induced by LTB4. On the basis of these assays, a structure-affinity relationship was investigated. Optimization of the acid chain length and omega-substitution of a phenyl group on the lipophilic tail were shown to be critical for binding activity. These modifications led to the discovery of compounds with submicromolar potency and selective BLTR antagonism. The most potent compound 3b alpha (IC50 = 250 nM) was found to significantly inhibit oedema formation in a topical model of phorbolester-induced inflammation. Substantial improvement of in vitro potency was achieved by modification of the carboxylic acid function leading to the identification of the N,N-dimethylamide series. Compound 5b alpha, free of agonist activity, displayed higher potency in receptor binding with an IC50 of 40 nM. These results support the hypothesis that the spatial relationship between the carboxylic acid and allylic hydroxyl functions is crucial for high binding affinity with BLTR.