ethyl 9-methylsulphonamidocarbonylmethyl-4-oxo-4,5-dihydro-10H-imidazo[1,2-a]indeno[1,2-e]pyrazine-2-carboxylate | 193814-20-9

• 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: ethyl 9-methylsulphonamidocarbonylmethyl-4-oxo-4,5-dihydro-10H-imidazo[1,2-a]indeno[1,2-e]pyrazine-2-carboxylate
• 英文别名: ethyl 14-[2-(methanesulfonamido)-2-oxoethyl]-7-oxo-2,5,8-triazatetracyclo[7.7.0.02,6.010,15]hexadeca-1(9),3,5,10,12,14-hexaene-4-carboxylate
• CAS: 193814-20-9
• 化学式: C₁₉H₁₈N₄O₆S
• 分子量: 430.441
• InChiKey: XXRIUAACPDEYLJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  145
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl 9-methylsulphonamidocarbonylmethyl-4-oxo-4,5-dihydro-10H-imidazo[1,2-a]indeno[1,2-e]pyrazine-2-carboxylate 在 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 生成 9-methylsulphonamidocarbonylmethyl-4-oxo-4,5-dihydro-10H-imidazo[1,2-a]indeno[1,2-e]pyrazine-2-carboxylic acid
  参考文献：
  名称：

  5H,10H-imidazo[1,2-a]indeno[1,2-e]pyrazine-4-one derivatives,

  摘要：

  化合物的化学式（I），其中R是氢原子或--COOH，-烷基-COOH，--PO.sub.3 H.sub.2，--CH.sub.2 --PO.sub.3 H.sub.2或--CH.dbd.CH--COOH基团，或被羧基取代的苯基基团，R.sub.1是烷基-CN，-烷基-COOH，-烷基-Het，烷基-PO.sub.3 H.sub.2或-烷基-CO--NH--SO.sub.2 R.sub.2基团，R.sub.2是烷基或苯基基团，烷基是烷基基团，Het是含有1-9个碳原子和一个或多个异原子（O、S和N）的饱和或不饱和单环或多环杂环环，该杂环环可以选择性地被一个或多个烷基，苯基或苯基烷基基团取代，但是当R是氢原子或--COOH或--PO.sub.3 H.sub.2基团时，R.sub.1不能是-烷基-COOH，其同分异构体，消旋混合物，对映异构体和非对映异构体，以及其盐，其制备方法，其中间体和含有该化合物的药物已被披露。化合物的化学式（I）具有有价值的药理学性质，并且是α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体的拮抗剂，也被称为quisqualate受体。此外，化合物的化学式（I）是N-甲基-D-天冬氨酸（NMDA）受体的非竞争性拮抗剂，特别是NMDA受体甘氨酸调节剂位点的配体。

  公开号：

  US05990108A1
• 作为产物：
  描述：

  3-[2-(羧甲基)苯基]丙酸 在 盐酸 、 硫酸 、 ammonium acetate 、 氢溴酸 、 溴 、 potassium carbonate 、 溶剂黄146 、 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 丙酮 、 甲苯 为溶剂， 反应 33.5h， 生成 ethyl 9-methylsulphonamidocarbonylmethyl-4-oxo-4,5-dihydro-10H-imidazo[1,2-a]indeno[1,2-e]pyrazine-2-carboxylate
  参考文献：
  名称：

  Bioisosteres of 9-Carboxymethyl-4-oxo-imidazo[1,2- a ]indeno[1,2- e ]pyrazin-2-carboxylic acid derivatives. Progress towards selective, potent In Vivo AMPA antagonists with longer durations of action

  摘要：

  A novel series of 2- and 9-disubstituted heterocyclic-fused 4-oxo-indeno[1,2-e]pyrazin derivatives was synthesized. One of them, the 9-(1 H-tetrazol-5-ylmethyl)-4-oxo-5,10-dihydroimidazo[1,2-a]indeno[1,2-e]pyrazin-2-yl phosphonic acid 4i exhibited a strong and a selective binding affinity for the AMPA receptor (IC50 = 13 nM) and demonstrated potent antagonist activity (IC50 = 6 nM) at the ionotropic AMPA receptor. This compound also displayed good anticonvulsant properties against electrically-induced convulsions after ip and iv administration with ED50 values between 0.8 and 1 mg/kg. Furthermore, a strong increase in potency was observed when given iv 3 h before test (ED50 = 3.5 instead of 25.6 mg/kg for the corresponding 9-carboxymethyl-2-carboxylic acid analogue). These data confirmed that there is an advantage in replacing the classical carboxy substituents by their bioisosteres such as tetrazole or phosphonic acid groups. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00592-8

文献信息

• 5H,10H-imidazo[1,2-a]indeno[1,2-e]pyrazine-4-one derivatives,
  申请人：Rhone Poulenc Rorer S.A.

  公开号：US05990108A1

  公开（公告）日：1999-11-23

  Compounds of formula (I), wherein R is a hydrogen atom or a --COOH, -alk-COOH, --PO.sub.3 H.sub.2, --CH.sub.2 --PO.sub.3 H.sub.2, or --CH.dbd.CH--COOH radical, or a phenyl radical substituted by a carboxy radical, R.sub.1 is an alk-CN, -alk-COOH, -alk-Het, alk-PO.sub.3 H.sub.2 or -alk-CO--NH--SO.sub.2 R.sub.2 radical, R.sub.2 is an alkyl or phenyl radical, alk is an alkyl radical, Het is a saturated or unsaturated mono- or polycyclic heterocyclic ring containing 1-9 carbon atoms and one or more heteroatoms selected from O, S and N, said heterocyclic ring optionally being substituted by one or more alkyl, phenyl or phenylalkyl radicals, with the proviso that when R is a hydrogen atom or a --COOH or --PO.sub.3 H.sub.2 radical, R.sub.1 cannot be -alk-COOH, isomers, racemic mixtures, enantiomers and diastereoisomers thereof, salts thereof, the preparation thereof, intermediates thereof and drugs containing said compounds, are disclosed. The compounds of formula (I) have valuable pharmacological properties and are antagonists of the .alpha.-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor also known as the quisqualate receptor. Furthermore, the compounds of formula (I) are non-competitive antagonists of the N-methyl-D-aspartate (NMDA) receptor, and specifically ligands for NMDA receptor glycine modulator sites. ##STR1##

  化合物的化学式（I），其中R是氢原子或--COOH，-烷基-COOH，--PO.sub.3 H.sub.2，--CH.sub.2 --PO.sub.3 H.sub.2或--CH.dbd.CH--COOH基团，或被羧基取代的苯基基团，R.sub.1是烷基-CN，-烷基-COOH，-烷基-Het，烷基-PO.sub.3 H.sub.2或-烷基-CO--NH--SO.sub.2 R.sub.2基团，R.sub.2是烷基或苯基基团，烷基是烷基基团，Het是含有1-9个碳原子和一个或多个异原子（O、S和N）的饱和或不饱和单环或多环杂环环，该杂环环可以选择性地被一个或多个烷基，苯基或苯基烷基基团取代，但是当R是氢原子或--COOH或--PO.sub.3 H.sub.2基团时，R.sub.1不能是-烷基-COOH，其同分异构体，消旋混合物，对映异构体和非对映异构体，以及其盐，其制备方法，其中间体和含有该化合物的药物已被披露。化合物的化学式（I）具有有价值的药理学性质，并且是α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体的拮抗剂，也被称为quisqualate受体。此外，化合物的化学式（I）是N-甲基-D-天冬氨酸（NMDA）受体的非竞争性拮抗剂，特别是NMDA受体甘氨酸调节剂位点的配体。
• US06100264
  申请人：——

  公开号：——

  公开（公告）日：——
• US5990108A
  申请人：——

  公开号：US5990108A

  公开（公告）日：1999-11-23
• US6100264A
  申请人：——

  公开号：US6100264A

  公开（公告）日：2000-08-08
• Bioisosteres of 9-Carboxymethyl-4-oxo-imidazo[1,2- a ]indeno[1,2- e ]pyrazin-2-carboxylic acid derivatives. Progress towards selective, potent In Vivo AMPA antagonists with longer durations of action
  作者：Patrick Jimonet、Georg Andrees Bohme、Jean Bouquerel、Alain Boireau、Dominique Damour、Marc Williams Debono、Arielle Genevois-Borella、Jean-Claude Hardy、Philippe Hubert、Franco Manfré、Patrick Nemecek、Jeremy Pratt、John C.R. Randle、Yves Ribeill、Jean-Marie Stutzmann、Marc Vuilhorgne、Serge Mignani

  DOI：10.1016/s0960-894x(00)00592-8

  日期：2001.1

  A novel series of 2- and 9-disubstituted heterocyclic-fused 4-oxo-indeno[1,2-e]pyrazin derivatives was synthesized. One of them, the 9-(1 H-tetrazol-5-ylmethyl)-4-oxo-5,10-dihydroimidazo[1,2-a]indeno[1,2-e]pyrazin-2-yl phosphonic acid 4i exhibited a strong and a selective binding affinity for the AMPA receptor (IC50 = 13 nM) and demonstrated potent antagonist activity (IC50 = 6 nM) at the ionotropic AMPA receptor. This compound also displayed good anticonvulsant properties against electrically-induced convulsions after ip and iv administration with ED50 values between 0.8 and 1 mg/kg. Furthermore, a strong increase in potency was observed when given iv 3 h before test (ED50 = 3.5 instead of 25.6 mg/kg for the corresponding 9-carboxymethyl-2-carboxylic acid analogue). These data confirmed that there is an advantage in replacing the classical carboxy substituents by their bioisosteres such as tetrazole or phosphonic acid groups. (C) 2001 Elsevier Science Ltd. All rights reserved.