(E)-2-(1-((benzyloxy)methyl)-4-((Z)-2-bromovinyl)-2-chloro-1H-imidazol-5-yl)-3-(4-methoxy-3,5-dimethylphenyl)-N-methyl-acrylamide | 1254361-82-4

• 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)-2-(1-((benzyloxy)methyl)-4-((Z)-2-bromovinyl)-2-chloro-1H-imidazol-5-yl)-3-(4-methoxy-3,5-dimethylphenyl)-N-methyl-acrylamide
• 英文别名: (E)-2-[5-[(Z)-2-bromoethenyl]-2-chloro-3-(phenylmethoxymethyl)imidazol-4-yl]-3-(4-methoxy-3,5-dimethylphenyl)-N-methylprop-2-enamide
• CAS: 1254361-82-4
• 化学式: C₂₆H₂₇BrClN₃O₃
• 分子量: 544.876
• InChiKey: YVKGJUQVKJREPC-XMQYJYGRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  65.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (E)-2-(1-((benzyloxy)methyl)-4-((Z)-2-bromovinyl)-2-chloro-1H-imidazol-5-yl)-3-(4-methoxy-3,5-dimethylphenyl)-N-methyl-acrylamide 在 potassium phosphate 、 copper(l) iodide 、 N,N'-二甲基乙二胺 作用下， 以 甲苯 为溶剂， 反应 21.0h， 以65%的产率得到(E)-3-((benzyloxy)methyl)-2-chloro-4-(4-methoxy-3,5-dimethylbenzylidene)-6-methyl-4,6-dihydroimidazo[4,5-d]azepin-5(3H)-one
  参考文献：
  名称：

  Synthetic Analogues of the Microtubule-Stabilizing Sponge Alkaloid Ceratamine A Are More Active than the Natural Product

  摘要：

  Desbromoceratamine A (3) exhibits significantly less potent activity than the natural product ceratamine A (1) in a cell-based assay for antimitotic activity. Synthesis of the ceratamine A analogue 4 has shown that replacing the bromine atoms in the natural product with methyl groups generates an analogue that is more active than natural ceratamine A (1). Further enhancement of the antimitotic activity of the ceratamine pharmacophore has been achieved in the synthetic analogue 33, which has both bromine atoms replaced with methyl groups and an additional methyl substituent on the amino nitrogen at C-2. An efficient synthetic route has been developed to 33 that should enable the first in vivo evaluation of the new ceratamine microtubule-stabilizing pharmacophore and has provided several additional analogues for structure-activity relationship evaluation.

  DOI：

  10.1021/jm101012q
• 作为产物：
  描述：

  (E)-2-(1-((benzyloxy)methyl)-2-chloro-4-formyl-1H-imidazol-5-yl)-3-(4-methoxy-3,5-dimethylphenyl)-N-methylacrylamide 、 溴甲基三苯基溴化磷 在 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 反应 2.67h， 以84%的产率得到(E)-2-(1-((benzyloxy)methyl)-4-((Z)-2-bromovinyl)-2-chloro-1H-imidazol-5-yl)-3-(4-methoxy-3,5-dimethylphenyl)-N-methyl-acrylamide
  参考文献：
  名称：

  Synthetic Analogues of the Microtubule-Stabilizing Sponge Alkaloid Ceratamine A Are More Active than the Natural Product

  摘要：

  Desbromoceratamine A (3) exhibits significantly less potent activity than the natural product ceratamine A (1) in a cell-based assay for antimitotic activity. Synthesis of the ceratamine A analogue 4 has shown that replacing the bromine atoms in the natural product with methyl groups generates an analogue that is more active than natural ceratamine A (1). Further enhancement of the antimitotic activity of the ceratamine pharmacophore has been achieved in the synthetic analogue 33, which has both bromine atoms replaced with methyl groups and an additional methyl substituent on the amino nitrogen at C-2. An efficient synthetic route has been developed to 33 that should enable the first in vivo evaluation of the new ceratamine microtubule-stabilizing pharmacophore and has provided several additional analogues for structure-activity relationship evaluation.

  DOI：

  10.1021/jm101012q

文献信息

• Synthetic Analogues of the Microtubule-Stabilizing Sponge Alkaloid Ceratamine A Are More Active than the Natural Product
  作者：Matt Nodwell、Carla Zimmerman、Michel Roberge、Raymond J. Andersen

  DOI：10.1021/jm101012q

  日期：2010.11.11

  Desbromoceratamine A (3) exhibits significantly less potent activity than the natural product ceratamine A (1) in a cell-based assay for antimitotic activity. Synthesis of the ceratamine A analogue 4 has shown that replacing the bromine atoms in the natural product with methyl groups generates an analogue that is more active than natural ceratamine A (1). Further enhancement of the antimitotic activity of the ceratamine pharmacophore has been achieved in the synthetic analogue 33, which has both bromine atoms replaced with methyl groups and an additional methyl substituent on the amino nitrogen at C-2. An efficient synthetic route has been developed to 33 that should enable the first in vivo evaluation of the new ceratamine microtubule-stabilizing pharmacophore and has provided several additional analogues for structure-activity relationship evaluation.