(E)-3[2-(1-adamantylcarbamoyl)ethenyl]4,6-dichloroindole-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: (E)-3[2-(1-adamantylcarbamoyl)ethenyl]4,6-dichloroindole-2-carboxylic acid
• 英文别名: 3-[2-(1-adamantylcarbamoyl)ethenyl]4,6-dichloroindole-2-carboxylic acid；3-[(E)-3-(1-adamantylamino)-3-oxoprop-1-enyl]-4,6-dichloro-1H-indole-2-carboxylic acid
• 化学式: C₂₂H₂₂Cl₂N₂O₃
• 分子量: 433.334
• InChiKey: CZQZPICMDBADCR-OWOJBTEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  82.2
• 氢给体数：
  3
• 氢受体数：
  3

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 lithium hydroxide 、 甲酸 、 三苯基膦 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 乙腈 为溶剂， 反应 15.0h， 生成 (E)-3[2-(1-adamantylcarbamoyl)ethenyl]4,6-dichloroindole-2-carboxylic acid
  参考文献：
  名称：

  Cycloalkyl Indole-2-Carboxylates as Useful Tools for Mapping the "North-Eastern" Region 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 terminal phenyl ring belonging to the side chain present in the position C-3 has been replaced with a bridged cycloalkyl group was synthesized and evaluated for its pharmacological profile. Modelling studies on this class of novel glycine antagonist allowed us to identify an asymmetric lipophilic pocket present in the "North-Eastern" region of the pharmacophoric model of the glycine binding site associated to the NMDA receptor. Among the derivatives prepared, 3-[2-(1-adamantylaminocarbonyl)ethenyl]-4,6-dichloroindole-2-carboxylic acid 6b and 3-[2(norbornylaminocarbonyl)ethenyl]-4,6-dichloroindole-2-carboxylic acid 61 were found to be antagonists acting at the strychnine-insensitive glycine binding site, showing nanomolar affinity for the glycine binding site (K-i = 63 and 19 nM, respectively), coupled with high glutamate receptor selectivity (IC50 > 10(-5) M at the NMDA, AMPA, KA binding sites) and high in vivo potency after :systemic administration by inhibition of convulsion induced by NMDA in mice.

  DOI：

  10.1002/(sici)1521-4184(19993)332:3<73::aid-ardp73>3.0.co;2-5

文献信息

• Indole derivatives
  申请人：Glaxo Wellcome S.p.A.

  公开号：US05686461A1

  公开（公告）日：1997-11-11

  The invention relates to compounds of formula (I). ##STR1## or a salt, or metabolically labile ester thereof wherein R.sub.1 represents a group selected from halogen, alkyl, alkoxy, amino, alkylamino, dialkylamino, hydroxy, trifluoromethyl, trifluoromethoxy, nitro, cyano, SO.sub.2 R.sub.3 or COR.sub.3 wherein R.sub.3 represents hydroxy, methoxy, or amino; m is zero or an integer 1 or 2; A represents an ethynyl group or an optionally substituted ethenyl group; X represents a bond or a C.sub.1-4 alkylene chain; R.sub.2 represents a bridged cycloalkyl or bridged heterocyclic group; which are antagonists of excitatory amino acids, to processes for their preparation and to their use in medicine.

  该发明涉及式（I）的化合物。##STR1##或其盐或代谢易变酯，其中R.sub.1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.2R.sub.3或COR.sub.3中选择的基团，其中R.sub.3代表羟基，甲氧基或氨基; m为零或整数1或2; A代表乙炔基或可选取代的乙烯基; X代表键或C.sub.1-4烷基链; R.sub.2代表桥式环烷基或桥式杂环基; 这些化合物是兴奋性氨基酸拮抗剂，用于制备这些化合物的方法以及在医学上的应用。
• INDOLE DERIVATIVES AS ANTAGONISTS OF EXCITATORY AMINO ACIDS
  申请人：GLAXO S.p.A.

  公开号：EP0699186A1

  公开（公告）日：1996-03-06
• US5686461A
  申请人：——

  公开号：US5686461A

  公开（公告）日：1997-11-11
• [EN] INDOLE DERIVATIVES AS ANTAGONISTS OF EXCITATORY AMINO ACIDS<br/>[FR] DERIVES D'INDOLE COMME ANTAGONISTES D'ACIDES AMINES EXCITATEURS
  申请人：GLAXO S.P.A.

  公开号：WO1994020465A1

  公开（公告）日：1994-09-15

  (EN) The invention relates to compounds of formula (I) or a salt, or metabolically labile ester thereof wherein R1 represents a group selected from halogen, alkyl, alkoxy, amino, alkylamino, dialkylamino, hydroxy, trifluoromethyl, trifluoromethoxy, nitro, cyano, SO2R3 or COR3 wherein R3 represents hydroxy, methoxy, or amino; m is zero or an integer 1 or 2; A represents an ethynyl group or an optionally substituted ethenyl group; X represents a bond or a C1-4 alkylene chain; R2 represents a bridged cycloalkyl or bridged heterocyclic group; which are antagonists of excitatory amino acids, to processes for their preparation and to their use in medicine.(FR) Composés répondant à la formule (I), leur sel ou leur ester métaboliquement labile. Dans ladite formule, R1 représente un groupe sélectionné parmi hydrogène, alkyle, alcoxy, amino, alkylamino, dialkylamino, hydroxy, trifluorométhyle, trifluorométhoxy, nitro, cyano, SO2R3 ou COR3 où R3 représente hydroxy, méthoxy ou amino; m est 0, 1 ou 2; A représente un groupe éthynyle ou un groupe éthényle éventuellement substitué; X représente une liaison ou une chaîne alkylène C1-4; et R2 représente un groupe cycloalkyle ou hétérocyclique ponté. Ces composés sont des antagonistes des acides aminés excitateurs. On a également prévu leurs procédés de préparation et leurs utilisations médicales.