10-tert-butoxycarbonylamino-5H,10H-imidazo[1,2-a]indeno[1,2-e]pyrazin-4-one | 173155-30-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并[1，2-a]吡嗪-8-酮
• 英文名称: 10-tert-butoxycarbonylamino-5H,10H-imidazo[1,2-a]indeno[1,2-e]pyrazin-4-one
• 英文别名: tert-butyl N-(7-oxo-2,5,8-triazatetracyclo[7.7.0.02,6.010,15]hexadeca-1(9),3,5,10,12,14-hexaen-16-yl)carbamate
• CAS: 173155-30-1
• 化学式: C₁₈H₁₈N₄O₃
• 分子量: 338.366
• InChiKey: DIDHLHZLTWBWGU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  85.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  10-tert-butoxycarbonylamino-5H,10H-imidazo[1,2-a]indeno[1,2-e]pyrazin-4-one 在 sodium hydride 、 三氟乙酸 作用下， 反应 5.0h， 生成 Spiro[2,5,8-triazatetracyclo[7.7.0.02,6.010,15]hexadeca-1(9),3,5,10,12,14-hexaene-16,2'-pyrrolidine]-7-one
  参考文献：
  名称：

  Spiro-imidazo[1,2-a]indeno[1,2-e]pyrazine-4-one derivatives are mixed AMPA and NMDA glycine-site antagonists active in vivo

  摘要：

  Original spiro-imidazo[1,2-a]indeno[1,2-e]pyrazine-4-one derivatives were synthesised and led to the identification of 3e which showed good affinities for both the AMPA and the NMDA glycine-site receptors, and displayed good anticonvulsant effects after i.p. and i.v. administrations in the electroshock-induced convulsion assay in mice. The corresponding dextrorotatory isomer (+)-3e was notably more potent than the levorotatory isomer (-)-3e in in vitro and in vivo assays. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(99)00502-8
• 作为产物：
  描述：

  5H,10H-imidazo<1,2-a>indeno<1,2-e>pyrazin-4-one 在 盐酸 、 iAmNO₂ 、 sodium hydride 、 三乙胺 、 锌 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 25.0h， 生成 10-tert-butoxycarbonylamino-5H,10H-imidazo[1,2-a]indeno[1,2-e]pyrazin-4-one
  参考文献：
  名称：

  Spiro-imidazo[1,2-a]indeno[1,2-e]pyrazine-4-one derivatives are mixed AMPA and NMDA glycine-site antagonists active in vivo

  摘要：

  Original spiro-imidazo[1,2-a]indeno[1,2-e]pyrazine-4-one derivatives were synthesised and led to the identification of 3e which showed good affinities for both the AMPA and the NMDA glycine-site receptors, and displayed good anticonvulsant effects after i.p. and i.v. administrations in the electroshock-induced convulsion assay in mice. The corresponding dextrorotatory isomer (+)-3e was notably more potent than the levorotatory isomer (-)-3e in in vitro and in vivo assays. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(99)00502-8

文献信息

• [EN] SPIRO[HETEROCYCLE-IMIDAZO[1,2-a]INDENO[1,2-e]PYRAZINE]-4'-ONES, PREPARATION THEREOF AND DRUGS CONTAINING SAME<br/>[FR] SPIRO[HETEROCYCLE-IMIDAZO[1,2-a]INDENO[1,2-e]PYRAZINE]-4'-ONES, LEUR PREPARATION ET LES MEDICAMENTS LES CONTENANT
  申请人：RHONE-POULENC RORER S.A.

  公开号：WO1996014318A1

  公开（公告）日：1996-05-17

  (EN) Compounds of formula (I), wherein R3 and R4, taken together with the carbon atom to which they are attached, form (a) a 2- or 3-pyrrolidine ring, a 2- or 4-piperidine ring or a 2-azacycloheptane ring, said rings being optionally substituted at the nitrogen atom by an alkyl radical, -CHO, -COOR11, -CO-alk-COOR6, -CO-alk-NR6R12, -CO-alk-CONR6R8, -CO-COOR6, -CO-CH2-O-CH2-COOR6, -CO-CH2-S-CH2-COOR6, -CO-CH=CH-COOR6, -CO-alk, -CO-Ar'. -CO-alk-Ar', -CO-NH-Ar', -CO-NH-alk-Ar', -CO-Het, -CO-alk-Het, -CO-NH-Het, -CO-NH-alk-Het, -CO-NH2, -CO-NH-alk, -CO-N(alk)alk', -CS-NH2, -CS-NH-alk, -CS-NH-Ar', -CS-NH-Het, -alk-Het, -alk-NR6R8, -alk-COOR6, -alk-CO-NR6R8, -alk-Ar', -SO2-alk, -SO2-Ar or -CO-cycloalkyl, where the cycloalkyl is optionally 2-substituted by a carboxy radical; or (b) a 2-pyrrolidine-5-one ring. The compounds of formula (I) have useful pharmacological properties and are $g(a)-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists, said receptor also being known as the quisqualate receptor. Furthermore, the compounds of formula (I) are non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists, and especially NMDA receptor glycine modulation site ligands.(FR) Composés de formule (I), dans laquelle R3 et R4 forment ensemble avec l'atome de carbone auquel ils sont rattachés (a) un cycle 2- ou 3-pyrrolidine, un cycle 2- ou 4-pipéridine ou un cycle 2-azacycloheptane, ces cycles étant éventuellement substitués sur l'azote par un radical alkyle, -CHO, -COOR11, -CO-alk-COOR6, -CO-alk-NR6R12, -CO-alk-CONR6R8, -CO-COOR6, -CO-CH2-O-CH2-COOR6, -CO-CH2-S-CH2-COOR6, -CO-CH=CH-COOR6, -CO-alk, -CO-Ar', -CO-alk-Ar', -CO-NH-Ar', -CO-NH-alk-Ar', -CO-Het, -CO-alk-Het, -CO-NH-Het, -CO-NH-alk-Het, -CO-NH2, -CO-NH-alk, -CO-N(alk)alk', -CS-NH2, -CS-NH-alk, -CS-NH-Ar', -CS-NH-Het, -alk-Het, -alk-NR6R8, -alk-COOR6, -alk-CO-NR6R8, -alk-Ar', -SO2-alk, -SO2-Ar ou -CO-cycloalkyle dont le cycloalkyle est éventuellement substitué en -2 par un radical carboxy ou (b) un cycle 2-pyrrolidine-5-one. Les composés de formule (I) présentent des propriétés pharmacologiques intéressantes. Ces composés sont des antagonistes du récepteur de l'acide $g(a)-amino-3-hydroxy-5-méthyl-4-isoxazolepropionique (AMPA), connu aussi sous le nom de récepteur du quisqualate. Par ailleurs, les composés de formule (I) sont des antagonistes non compétitifs du récepteur N-méthyl-D-aspartate (NMDA) et, plus particulièrement, ce sont des ligands pour les sites modulateurs de la glycine du récepteur NMDA.

  化合物的化学式为（I），其中R3和R4与它们附着的碳原子共同形成（a）2-或3-吡咯烷环、2-或4-哌啶环或2-氮杂环庚烷环，这些环在氮原子上可以被烷基、-CHO、-COOR11、-CO-烷基-COOR6、-CO-烷基-NR6R12、-CO-烷基-CONR6R8、-CO-COOR6、-CO-CH2-O-CH2-COOR6、-CO-CH2-S-CH2-COOR6、-CO-CH=CH-COOR6、-CO-烷基、-CO-Ar'、-CO-烷基-Ar'、-CO-NH-Ar'、-CO-NH-烷基-Ar'、-CO-Het、-CO-烷基-Het、-CO-NH-Het、-CO-NH-烷基-Het、-CO-NH2、-CO-NH-烷基、-CO-N(烷基)烷'、-CS-NH2、-CS-NH-烷基、-CS-NH-Ar'、-CS-NH-Het、-烷基-Het、-烷基-NR6R8、-烷基-COOR6、-烷基-CO-NR6R8、-烷基-Ar'、-SO2-烷基、-SO2-Ar或-CO-环烷基，其中环烷基在2位可以被羧基取代；或（b）2-吡咯烷-5-酮环。化合物的化学式（I）具有有用的药理学性质，并且是$g(a)-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体拮抗剂，该受体也被称为喜马拉雅酸受体。此外，化合物的化学式（I）是非竞争性N-甲基-D-天门冬氨酸（NMDA）受体拮抗剂，尤其是NMDA受体甘氨酸调节位点配体。
• SPIRO HETEROCYCLE-IMIDAZO(1,2-a]INDENO(1,2-e]PYRAZINE]-4'-ONES, LEUR PREPARATION ET LES MEDICAMENTS LES CONTENANT
  申请人：RHONE-POULENC RORER S.A.

  公开号：EP0789699A1

  公开（公告）日：1997-08-20
• SPIRO[HETEROCYCLE-IMIDAZO[1,2-a]INDENO[1,2-e]PYRAZINE]-4'-ONES, LEUR PREPARATION ET LES MEDICAMENTS LES CONTENANT
  申请人：RHONE-POULENC RORER S.A.

  公开号：EP0789699B1

  公开（公告）日：1999-03-17
• Spiro-imidazo[1,2-a]indeno[1,2-e]pyrazine-4-one derivatives are mixed AMPA and NMDA glycine-site antagonists active in vivo
  作者：Patrick Jimonet、Alain Boireau、Michel Chevé、Dominique Damour、Arielle Genevois-Borella、Assunta Imperato、Jeremy Pratt、John C.R. Randle、Yves Ribeill、Jean-Marie Stutzmann、Serge Mignani

  DOI：10.1016/s0960-894x(99)00502-8

  日期：1999.10

  Original spiro-imidazo[1,2-a]indeno[1,2-e]pyrazine-4-one derivatives were synthesised and led to the identification of 3e which showed good affinities for both the AMPA and the NMDA glycine-site receptors, and displayed good anticonvulsant effects after i.p. and i.v. administrations in the electroshock-induced convulsion assay in mice. The corresponding dextrorotatory isomer (+)-3e was notably more potent than the levorotatory isomer (-)-3e in in vitro and in vivo assays. (C) 1999 Elsevier Science Ltd. All rights reserved.