1-tert-butoxycarbonyl-3-formyl-4,6-dichloroindole-2-carboxylic acid ethyl ester | 166974-61-4

• 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: 1-tert-butoxycarbonyl-3-formyl-4,6-dichloroindole-2-carboxylic acid ethyl ester
• 英文别名: ethyl 1-tert-butoxycarbonyl-3-formyl-4,6-dichloroindole-2-carboxylate；Ethyl 4,6-dichloro-3-formyl-1-tert-butoxycarbonyl-1H-indole-2-carboxylate；1-O-tert-butyl 2-O-ethyl 4,6-dichloro-3-formylindole-1,2-dicarboxylate
• CAS: 166974-61-4
• 化学式: C₁₇H₁₇Cl₂NO₅
• 分子量: 386.232
• InChiKey: MEDGIJROWDGAIB-UHFFFAOYSA-N

物化性质

• 沸点：
  517.0±60.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  74.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-tert-butoxycarbonyl-3-formyl-4,6-dichloroindole-2-carboxylic acid ethyl ester 在 1-羟基苯并三唑一水物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 3.0h， 生成 4,6-Dichloro-3-((Z)-2-fluoro-2-phenylcarbamoyl-vinyl)-indole-1,2-dicarboxylic acid 1-tert-butyl ester 2-ethyl ester
  参考文献：
  名称：

  Substituted Indole-2-carboxylates as Potent Antagonists of the Glycine Binding Site Associated with the NMDA Receptor

  摘要：

  A novel series of indole-2-carboxylate analogues of GV 150526 (1) in which the propenoic double bond was substituted with different "probes" or replaced by a isosteric cyclopropyl moiety were synthesized and evaluated for their affinity profile in order to obtain further information on the pharmacophoric model of the glycine binding site associated to the NMDA receptor.

  DOI：

  10.1002/(sici)1521-4184(19998)332:8<271::aid-ardp271>3.0.co;2-x
• 作为产物：
  描述：

  二碳酸二叔丁酯 、 4,6-二氯-3-甲酰基-1H-吲哚-2-甲酸乙酯 在 4-二甲氨基吡啶 氯化铵 、 Brine 、 crude title compound 、 乙酸乙酯 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 反应 2.0h， 生成 1-tert-butoxycarbonyl-3-formyl-4,6-dichloroindole-2-carboxylic acid ethyl ester
  参考文献：
  名称：

  Indole derivatives

  摘要：

  本发明涉及式##STR1##的化合物或其盐，或代谢不稳定的酯，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，桥式环烷基，杂环芳基，桥式杂环或可选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.pY(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从C.sub.1-6烷基中选择的羟基，氨基，烷基氨基或二烷基氨基取代，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至2; p为零或整数1至3; q为零或整数1至3，但p+q的和为1、2或3，这些化合物是兴奋性氨基酸的拮抗剂，在制备过程中和在医学上的其他用途中使用。

  公开号：

  US06100289A1

文献信息

• Indole derivatives as NMDA antagonists
  申请人：Glaxo Wellcome SpA

  公开号：US05962496A1

  公开（公告）日：1999-10-05

  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=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.

  本发明涉及公式##STR1##或其盐或代谢易变酯，其中R代表选自卤素，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.2R.sub.2或COR.sub.2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，桥联环烷基，杂环基，桥联杂环基或可选取代苯基或融合的双环碳环基；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，这些链可以被选自C.sub.1-6烷基的一或两个取代基取代，这些烷基可以被羟基，氨基，烷基氨基或二烷基氨基取代，或这些链可以被基团=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，可用于医学制剂的制备和其他用途。
• 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.
• INDOLE DERIVATIVES AS NMDA ANTAGONISTS
  申请人：GLAXO WELLCOME S.p.A.

  公开号：EP0723541A1

  公开（公告）日：1996-07-31
• 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