10-hydroxyimino-imidazo[1,2-a]indeno[1,2-e]pyrazine-4-one | 301823-82-5

• 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-hydroxyimino-imidazo[1,2-a]indeno[1,2-e]pyrazine-4-one
• CAS: 301823-82-5
• 化学式: C₁₃H₈N₄O₂
• 分子量: 252.232
• InChiKey: JDJMAUVIFMLJQK-UHFFFAOYSA-N

物化性质

• 密度：
  1.71±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.23
• 重原子数：
  19.0
• 可旋转键数：
  0.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  82.75
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  10-hydroxyimino-imidazo[1,2-a]indeno[1,2-e]pyrazine-4-one 在 palladium on activated charcoal 盐酸 、 硫酸 、 氢气 、 sodium hydride 、 potassium nitrate 、 锌 作用下， 以 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 22.5h， 生成 8-methylureido-10-amino-10-methyl-imidazo[1,2-a]indeno[1,2-e]pyrazine-4-one dihydrochloride
  参考文献：
  名称：

  8-Methylureido-10-amino-10-methyl-imidazo[1,2- a ]indeno[1,2- e ]pyrazine-4-ones: Highly In vivo Potent and Selective AMPA Receptor Antagonists

  摘要：

  Water soluble 8-methylureido-10-amino-10-methyl-imidazo[1,2-a]indeno[1,2-e]pyrazine-4-one 4 represents a novel class of highly potent and selective AMPA receptors antagonists with in vivo activity. The dextrorotatory isomer (+)-4 was found to display the highest affinity with an IC50 of 10 nM. It also exhibited very good anticonvulsant effects after ip, sc and iv administration in mice subjected to electrical convulsions (MES) and ip in audiogenic seizure-e in DBA/2 mice (ED50's less than or equal to 10 mg/kg). (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00161-9
• 作为产物：
  描述：

  5H,10H-imidazo<1,2-a>indeno<1,2-e>pyrazin-4-one 在 iAmNO₂ 、 sodium hydride 作用下， 以 二甲基亚砜 为溶剂， 反应 1.0h， 生成 10-hydroxyimino-imidazo[1,2-a]indeno[1,2-e]pyrazine-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

• Imidazo\x9b1,2-A! pyrazine-4-one, preparation thereof and drugs containing
  申请人：Rhone-Poulenc Rorer S.A.

  公开号：US05753657A1

  公开（公告）日：1998-05-19

  Compounds of formula (1) ##STR1## wherein either R is C.dbd.R.sub.3, C(R.sub.4)R.sub.5 or CH--R.sub.6, R.sub.1 and R.sub.2 are hydrogen, halogen, alkyl, alkoxy, amino, acylamino, --NH--CO--NH--Ar, --N.dbd.CH--N(alk)alk', nitro, cyano, phenyl, imidazolyl or SO.sub.3 H, R.sub.3 is oxygen, NOH, NO-alk-COOK or CH--R.sub.7, R.sub.4 is alkyl, -alk-Het or alk-Ar, R.sub.5 is alkyl, -alk-Het or -alk-Ar, or C(R.sub.4)R.sub.5 is cycloalkyl, R.sub.6 is hydroxy, alkyl, NR.sub.8 R.sub.9, -alk-OH, -alk-NR.sub.8 R.sub.9, -alk-Ar or -alk-Het, R.sub.7 is hydroxy, alkyl, phenyl, -alk-Ar, -alk-Het, NR.sub.10 R.sub.11 or a heterocyclic ring, R.sub.8 and R.sub.9 are alkyl, or R.sub.8 is hydrogen and R.sub.9 is hydrogen or alkyl, --COR.sub.12, --CSR.sub.30 or --SO.sub.2 R.sub.13, R.sub.10 and R.sub.11 are alkyl or cycloalkyl, R.sub.12 is alkyl, cycloalkyl, phenyl, --COO-alk, --CH.sub.2 --COOX, --CH.sub.2 NH.sub.2, --NH-alk, --NH--Ar, --NH.sub.2 or --NH-Het, R.sub.13 is alkyl or phenyl, R.sub.30 is --NH-alk, --NH--Ar, --NH.sub.2 or --NH-Het, R.sub.13 is alkyl or phenyl, R.sub.30 is --NH-alk, --NH--Ar, --NH.sub.2 or --NH-Het; or R is a 2-imidazolylmethyl radical and each of R.sub.1 and R.sub.2 is a hydrogen atom. The compounds of formula (I) are .alpha.-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 gylcine modulation site ligands.

  式（1）的化合物 ##STR1## 其中，R为C.dbd.R.sub.3，C（R.sub.4）R.sub.5或CH--R.sub.6，R.sub.1和R.sub.2为氢，卤素，烷基，烷氧基，氨基，酰胺基，--NH--CO--NH--Ar，--N.dbd.CH--N（烷基）烷'，硝基，氰基，苯基，咪唑基或SO.sub.3H，R.sub.3为氧，NOH，NO-烷基-COOK或CH--R.sub.7，R.sub.4为烷基，-烷基-杂环或烷基-芳基，R.sub.5为烷基，-烷基-杂环或-烷基-芳基，或C（R.sub.4）R.sub.5为环烷基，R.sub.6为羟基，烷基，NR.sub.8 R.sub.9，-烷基-OH，-烷基-NR.sub.8 R.sub.9，-烷基-Ar或-烷基-Het，R.sub.7为羟基，烷基，苯基，-烷基-Ar，-烷基-Het，NR.sub.10 R.sub.11或杂环环，R.sub.8和R.sub.9为烷基，或R.sub.8为氢，R.sub.9为氢或烷基，--COR.sub.12，--CSR.sub.30或--SO.sub.2 R.sub.13，R.sub.10和R.sub.11为烷基或环烷基，R.sub.12为烷基，环烷基，苯基，--COO-烷基，--CH.sub.2--COOX，--CH.sub.2 NH.sub.2，--NH-烷基，--NH--Ar，--NH.sub.2或--NH-Het，R.sub.13为烷基或苯基，R.sub.30为--NH-烷基，--NH--Ar，--NH.sub.2或--NH-Het，或R为2-咪唑基甲基基团，R.sub.1和R.sub.2均为氢原子。公式（I）的化合物是.alpha.-氨基-3-羟基-5-甲基-4-异噁唑丙酸（AMPA）受体拮抗剂，该受体也被称为喜马拉雅酸受体。此外，公式（I）的化合物是非竞争性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。
• Imidazo (1,2-A)-Indeno (1,2-E) pyrazin-4-one derivatives and
  申请人：Rhone-Poulenc Rorer S.A.

  公开号：US05807859A1

  公开（公告）日：1998-09-15

  Pharmaceutical compositions containing, as the active principle, compounds of formula (I): ##STR1## wherein R, R.sub.1 and R.sub.2 are as defined in the description, or salts thereof, the novel compounds of formula (I), and the preparation thereof. The compounds of formula (I) have valuable pharmacological properties and are alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists, this receptor also being known as the quisqualate receptor. Furthermore, the compounds of formula (I) are non-competitive N-methyl-D-aspartate (NDMA) receptor antagonists, and particularly NMDA receptor glycine modulation site ligands.

  含有化合物(I)的制药组合物作为活性成分，其中化合物(I)的结构式如下：##STR1## 其中R、R.sub.1和R.sub.2如描述中所定义，或其盐，化合物(I)的制备方法。化合物(I)具有有价值的药理学特性，并且是α-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(I)是非竞争性N-甲基-D-天门冬氨酸（NDMA）受体拮抗剂，特别是NMDA受体甘氨酸调节位点配体。