ethyl (3S,4aR,6S,8aR)-6-((4-ethoxycarbonyl-1H-imidazol-1-yl)methyl)-2-(methoxycarbonyl)-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylate | 346421-20-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: ethyl (3S,4aR,6S,8aR)-6-((4-ethoxycarbonyl-1H-imidazol-1-yl)methyl)-2-(methoxycarbonyl)-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylate
• 英文别名: [3S,4aR,6S,8aR]-ethyl-6-((4-ethoxycarbonyl-1H-imidazol-1-yl)methyl)-2-(methoxycarbonyl)-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylate；3-O-ethyl 2-O-methyl (3S,4aR,6S,8aR)-6-[(4-ethoxycarbonylimidazol-1-yl)methyl]-3,4,4a,5,6,7,8,8a-octahydro-1H-isoquinoline-2,3-dicarboxylate
• CAS: 346421-20-3
• 化学式: C₂₁H₃₁N₃O₆
• 分子量: 421.494
• InChiKey: TZLOEQYEYFAMQB-CUSZFKRNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  100
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl (3S,4aR,6S,8aR)-6-((4-ethoxycarbonyl-1H-imidazol-1-yl)methyl)-2-(methoxycarbonyl)-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylate 在 盐酸 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 生成 (3S,4aR,6S,8aR)-6-(4-carboxyimidazol-1-ylmethyl)decahydroisoquinoline-3-carboxylic acid dihydrocloride
  参考文献：
  名称：

  Ethyl (3S,4aR,6S,8aR)-6-(4-Ethoxycar- bonylimidazol-1-ylmethyl)decahydroiso- quinoline-3-carboxylic Ester:  A Prodrug of a GluR5 Kainate Receptor Antagonist Active in Two Animal Models of Acute Migraine

  摘要：

  Amino diacid 3, a highly selective competitive GluR5 kainate receptor antagonist, exhibited high GluR5 receptor affinity and selectivity over other glutamate receptors. Its diethyl ester prodrug 4 was orally active in two models of migraine: the neurogenic dural plasma protein extravasation model and the nucleus caudalis c-fos expression model. These data suggest that a GluR5 kainate receptor antagonist might be an efficacious antimigraine therapy with a novel mechanism of action.

  DOI：

  10.1021/jm025548q
• 作为产物：
  描述：

  Ethyl (3S,4aR,6S,8aR)-6-(hydroxymethyl)-2-(methoxycarbonyl)-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylate 在 sodium hydride 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 生成 ethyl (3S,4aR,6S,8aR)-6-((4-ethoxycarbonyl-1H-imidazol-1-yl)methyl)-2-(methoxycarbonyl)-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylate
  参考文献：
  名称：

  Ethyl (3S,4aR,6S,8aR)-6-(4-Ethoxycar- bonylimidazol-1-ylmethyl)decahydroiso- quinoline-3-carboxylic Ester:  A Prodrug of a GluR5 Kainate Receptor Antagonist Active in Two Animal Models of Acute Migraine

  摘要：

  Amino diacid 3, a highly selective competitive GluR5 kainate receptor antagonist, exhibited high GluR5 receptor affinity and selectivity over other glutamate receptors. Its diethyl ester prodrug 4 was orally active in two models of migraine: the neurogenic dural plasma protein extravasation model and the nucleus caudalis c-fos expression model. These data suggest that a GluR5 kainate receptor antagonist might be an efficacious antimigraine therapy with a novel mechanism of action.

  DOI：

  10.1021/jm025548q

文献信息

• Selective iglur5 receptor antagonists
  申请人：——

  公开号：US20030055081A1

  公开（公告）日：2003-03-20

  The present invention provides compounds of formula (I): wherein W represents hydrogen, C 1 -C 4 alkyl, —CH 2 CO 2 H, or CO 2 H; and X represents hydrogen, C 1 -C 4 alkyl, —CH 2 CO 2 H, or CO 2 H; with the proviso that at least one of W or X must be other than hydrogen; or a prodrug or a pharmaceutically acceptable salt thereof; which are useful for treating migraine.

  本发明提供式（I）的化合物：其中W代表氢，C1-C4烷基，—CH2CO2H或CO2H；X代表氢，C1-C4烷基，—CH2CO2H或CO2H；但须满足W或X中至少有一个不是氢；或其前药或药学上可接受的盐；用于治疗偏头痛。
• US6579886B2
  申请人：——

  公开号：US6579886B2

  公开（公告）日：2003-06-17
• Ethyl (3<i>S</i>,4a<i>R</i>,6<i>S</i>,8a<i>R</i>)-6-(4-Ethoxycar- bonylimidazol-1-ylmethyl)decahydroiso- quinoline-3-carboxylic Ester:  A Prodrug of a GluR5 Kainate Receptor Antagonist Active in Two Animal Models of Acute Migraine
  作者：Sandra A. Filla、Mark A. Winter、Kirk W. Johnson、David Bleakman、Michael G. Bell、Thomas J. Bleisch、Ana M. Castaño、Amy Clemens-Smith、Miriam del Prado、Donna K. Dieckman、Esteban Dominguez、Ana Escribano、Ken H. Ho、Kevin J. Hudziak、Mary A. Katofiasc、Jose A. Martinez-Perez、Ana Mateo、Brian M. Mathes、Edward L. Mattiuz、Ann Marie L. Ogden、Lee A. Phebus、Douglas R. Stack、Robert E. Stratford、Paul L. Ornstein

  DOI：10.1021/jm025548q

  日期：2002.9.1

  Amino diacid 3, a highly selective competitive GluR5 kainate receptor antagonist, exhibited high GluR5 receptor affinity and selectivity over other glutamate receptors. Its diethyl ester prodrug 4 was orally active in two models of migraine: the neurogenic dural plasma protein extravasation model and the nucleus caudalis c-fos expression model. These data suggest that a GluR5 kainate receptor antagonist might be an efficacious antimigraine therapy with a novel mechanism of action.