(E)-methyl 3-(1-((E)-1-(4-chlorophenyl)-3-hydroxy-4,4-dimethylpent-1-en-2-yl)-1H-imidazol-5-yl)acrylate | 1252026-84-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (E)-methyl 3-(1-((E)-1-(4-chlorophenyl)-3-hydroxy-4,4-dimethylpent-1-en-2-yl)-1H-imidazol-5-yl)acrylate
• 英文别名: DSI-505ME
• CAS: 1252026-84-8
• 化学式: C₂₀H₂₃ClN₂O₃
• 分子量: 374.867
• InChiKey: KBWWLQXYJIIFEG-BSDMPFPKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.13
• 重原子数：
  26.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  64.35
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  DSI-502 、 O,O'-双(2,2,2-三氟乙基)磷乙酸甲酯 在 sodium hydride 作用下， 以 四氢呋喃 、 mineral oil 为溶剂， 反应 1.0h， 以32%的产率得到(E)-methyl 3-(1-((E)-1-(4-chlorophenyl)-3-hydroxy-4,4-dimethylpent-1-en-2-yl)-1H-imidazol-5-yl)acrylate
  参考文献：
  名称：

  Selectivity improvement of an azole inhibitor of CYP707A by replacing the monosubstituted azole with a disubstituted azole

  摘要：

  The plant growth-retardant uniconazole (UNI), a triazole inhibitor of gibberellin biosynthetic enzyme (CYP701A), inhibits multiple P450 enzymes including ABA 8'-hydroxylase (CYP707A), a key enzyme in ABA catabolism. Azole P450 inhibitors bind to a P450 active site by both coordinating to the heme-iron atom via sp(2) nitrogen and interacting with surrounding protein residues through a lipophilic region. We hypothesized that poor selectivity of UNI may result from adopting a distinct conformation and orientation for different active sites. Based on this hypothesis, we designed and synthesized novel UNI analogs with a disubstituted azole ring (DSI). These analogs were expected to have higher selectivity than UNI because the added functional group may interact with the active site to restrict orientation of the molecule in the active site. DSI-505ME and DSI-505MZ, which have an imidazolyl group with a methyl 5-acrylate, strongly inhibited recombinant CYP707A3, with no growth-retardant effect. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.07.067