tert-butyl-[(E)-1-iodo-7-phenylhept-1-en-3-yl]oxy-dimethylsilane | 186689-76-9

• 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: tert-butyl-[(E)-1-iodo-7-phenylhept-1-en-3-yl]oxy-dimethylsilane
• CAS: 186689-76-9
• 化学式: C₁₉H₃₁IOSi
• 分子量: 430.445
• InChiKey: MGZFNFWORIJTPM-FOCLMDBBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.74
• 重原子数：
  22
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  tert-butyl-[(E)-1-iodo-7-phenylhept-1-en-3-yl]oxy-dimethylsilane 在 盐酸 、 正丁基锂 、 copper bromide*methyl sulfide 、 二异丙胺 、 3-甲氧基-3-甲基丁-1-炔 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 80.0h， 生成 [(1R,3R)-1-Hydroxy-3-((E)-(R)-3-hydroxy-7-phenyl-hept-1-enyl)-cyclohexyl]-acetic acid ethyl ester
  参考文献：
  名称：

  Hullot, Pierre; Poudrel, Jean-Marc; Muller, Agnes, Arzneimittel-Forschung/Drug Research, 1997, vol. 47, # 1, p. 51 - 58

  摘要：

  DOI：
• 作为产物：
  描述：

  6-苯基-2-己酮 在 盐酸 、 sodium tetrahydroborate 、 三氯化铝 、 氯化亚砜 、 sodium ethanolate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 sodium iodide 作用下， 以 乙醚 、 乙醇 、 二氯甲烷 、 水 、 丙酮 、 甲苯 为溶剂， 反应 53.5h， 生成 tert-butyl-[(E)-1-iodo-7-phenylhept-1-en-3-yl]oxy-dimethylsilane
  参考文献：
  名称：

  Hullot, Pierre; Poudrel, Jean-Marc; Muller, Agnes, Arzneimittel-Forschung/Drug Research, 1997, vol. 47, # 1, p. 51 - 58

  摘要：

  DOI：

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.