4-(1H-tetrazol-5-ylmethyl)-indan-1-one | 193813-83-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 4-(1H-tetrazol-5-ylmethyl)-indan-1-one
• 英文别名: 4-(2H-tetrazol-5-ylmethyl)-2,3-dihydroinden-1-one
• CAS: 193813-83-1
• 化学式: C₁₁H₁₀N₄O
• 分子量: 214.227
• InChiKey: RIJLXPKWCUVFKU-UHFFFAOYSA-N

物化性质

• 沸点：
  474.7±55.0 °C(Predicted)
• 密度：
  1.405±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  71.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(1H-tetrazol-5-ylmethyl)-indan-1-one 、 diethyl 2-ethoxycarbonylimidazole-4-phosphonate 生成
  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
• 作为产物：
  描述：

  邻溴氰苄 在 sodium azide 、 氯化铵 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 4-(1H-tetrazol-5-ylmethyl)-indan-1-one
  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

• DERIVES DE 5H,10H-IMIDAZO[1,2-a]INDENO[1,2-e]PYRAZINE-4-ONE ANTAGONISTES DES RECEPTEURS AMPA ET NMDA, LEUR PREPARATION, LEURS INTERMEDIAIRES ET LES MEDICAMENTS LES CONTENANT
  申请人：Aventis Pharma S.A.

  公开号：EP0880522B1

  公开（公告）日：2001-09-19
• 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.