4,6-dichloro-3-(3-oxo-2-phenyltetrahydropyridazin-4-ylidenemethyl)-1H-indole-2-carboxylic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 4,6-dichloro-3-(3-oxo-2-phenyltetrahydropyridazin-4-ylidenemethyl)-1H-indole-2-carboxylic acid
• 英文别名: (E) 4,6-dichloro-3-(3-oxo-2phenyl-tetrahydro-pyridazin-4-ylidenemethyl)-1H-indole-2-carboxylic acid；4,6-dichloro-3-[(E)-(3-oxo-2-phenyldiazinan-4-ylidene)methyl]-1H-indole-2-carboxylic acid
• 化学式: C₂₀H₁₅Cl₂N₃O₃
• 分子量: 416.263
• InChiKey: JJFSWPBIFDGHCP-DHZHZOJOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  85.4
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4,6-二氯-3-甲酰基-1H-吲哚-2-甲酸乙酯 在 4-二甲氨基吡啶 、 三氟乙酸 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 4.5h， 生成 4,6-dichloro-3-(3-oxo-2-phenyltetrahydropyridazin-4-ylidenemethyl)-1H-indole-2-carboxylic acid
  参考文献：
  名称：

  Synthesis and pharmacological characterisation of a conformationally restrained series of indole-2-carboxylates as in vivo potent glycine antagonists

  摘要：

  After the identification of GV150526, the indole-2-carboxylate template was further explored in order to identify novel potential anti-stroke agents. In particular, the SAR of the side chain present at the C-3 position of the indole nucleus was widely studied. In this paper, the synthesis and the pharmacological profile of a further class of conformationally restricted analogues of GV150526 as in vitro and in vivo potent glycine antagonists is reported. In particular, a pyrazolidinone derivative was identified as a potent neuroprotective agent in animal models of cerebral ischaemia. (C) 2001 Elsevier Science S.A. All rights reserved.

  DOI：

  10.1016/s0014-827x(01)01141-7

文献信息

• Indole derivatives
  申请人：Glaxo Wellcome SpA

  公开号：US05760059A1

  公开（公告）日：1998-06-02

  This invention relates to compounds of formula ##STR1## or a salt, or metabolically labile ester thereof wherein R represents a group selected from halogen, alkyl, alkoxy, amino, alkylamino, dialkylamino, hydroxy, trifluoromethyl, trifluoromethoxy, nitro, cyano, SO.sub.2 R.sub.2 or COR.sub.2 wherein R.sub.2 represents hydroxy, methoxy, amino, alkylamino, or dialkylamino; m is zero or an integer 1 or 2; R.sub.1 represents a cycloalkyl, bridged cycloalkyl, heteroaryl, bridged heterocyclic or optionally substituted phenyl or fused bicyclic carbocylic group; A represents a C.sub.1-4 alkylene chain or the chain (CH.sub.2).sub.p Y(CH.sub.2).sub.q wherein Y is O, S(O)n or NR.sub.3 and which chains may be substituted by one or two groups selected from C.sub.1-6 alkyl optionally substituted by hydroxy, amino, alkylamino or dialkylamino, or which chains may be substituted by the group .dbd.O; R.sub.3 represents hydrogen, alkyl or a nitrogen protecting group; n is zero or an integer from 1 to 2; p is zero or an integer from 1 to 3; q is zero or an integer from 1 to 3 with the proviso that the sum of p+q is 1, 2 or 3, which are antagonists of excitatory amino acids, to processes for the preparation and to other use in medicine.

  这项发明涉及以下式的化合物##STR1##或其盐，或代谢易降解的酯，其中R代表从卤素、烷基、烷氧基、氨基、烷基氨基、二烷基氨基、羟基、三氟甲基、三氟甲氧基、硝基、氰基、SO.sub.2 R.sub.2或COR.sub.2中选择的基团，其中R.sub.2代表羟基、甲氧基、氨基、烷基氨基或二烷基氨基；m为零或整数1或2；R.sub.1代表环烷基、桥环烷基、杂环烷基、桥接杂环烷基或可选择取代的苯基或融合的双环碳环基团；A代表C.sub.1-4烷基链或链(CH.sub.2).sub.p Y(CH.sub.2).sub.q，其中Y为O、S(O)n或NR.sub.3，这些链可以被一个或两个选自C.sub.1-6烷基（可选择地取代为羟基、氨基、烷基氨基或二烷基氨基）的基团取代，或这些链可以被基团.dbd.O取代；R.sub.3代表氢、烷基或氮保护基；n为零或整数1到2；p为零或整数1到3；q为零或整数1到3，但p+q的总和为1、2或3，这些化合物是兴奋性氨基酸的拮抗剂，用于制备的方法以及在医学中的其他用途。
• US5760059A
  申请人：——

  公开号：US5760059A

  公开（公告）日：1998-06-02
• US5962496A
  申请人：——

  公开号：US5962496A

  公开（公告）日：1999-10-05
• US6100289A
  申请人：——

  公开号：US6100289A

  公开（公告）日：2000-08-08
• Synthesis and pharmacological characterisation of a conformationally restrained series of indole-2-carboxylates as in vivo potent glycine antagonists
  作者：Romano Di Fabio、Gianluca Araldi、Davide Baraldi、Alfredo Cugola、Daniele Donati、Paola Gastaldi、Simone A Giacobbe、Fabrizio Micheli、Giorgio Pentassuglia

  DOI：10.1016/s0014-827x(01)01141-7

  日期：2001.9

  After the identification of GV150526, the indole-2-carboxylate template was further explored in order to identify novel potential anti-stroke agents. In particular, the SAR of the side chain present at the C-3 position of the indole nucleus was widely studied. In this paper, the synthesis and the pharmacological profile of a further class of conformationally restricted analogues of GV150526 as in vitro and in vivo potent glycine antagonists is reported. In particular, a pyrazolidinone derivative was identified as a potent neuroprotective agent in animal models of cerebral ischaemia. (C) 2001 Elsevier Science S.A. All rights reserved.