3-(2-(4-(3-chloro-2-methylphenyl)-1-piperazinyl)ethyl)-5,6-dimethoxy-1-(3,4-dimethoxybenzyl)-1H-indazole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 3-(2-(4-(3-chloro-2-methylphenyl)-1-piperazinyl)ethyl)-5,6-dimethoxy-1-(3,4-dimethoxybenzyl)-1H-indazole
• 英文别名: 3-[2-[4-(3-chloro-2-methylphenyl)piperazin-1-yl]ethyl]-1-[(3,4-dimethoxyphenyl)methyl]-5,6-dimethoxyindazole
• 化学式: C₃₁H₃₇ClN₄O₄
• 分子量: 565.112
• InChiKey: GVIFMXAPEOVXKO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  40
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  61.2
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  1-((5,6-dimethoxy-1-(3,4-dimethoxy-benzyl)-1H-indazol-3-yl)acetyl]-4-(3-chloro-2-methylphenyl)-piperazine 在 盐酸 、 potassium carbonate 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 3-(2-(4-(3-chloro-2-methylphenyl)-1-piperazinyl)ethyl)-5,6-dimethoxy-1-(3,4-dimethoxybenzyl)-1H-indazole
  参考文献：
  名称：

  Drug for neuroprotection

  摘要：

  揭示了一种含有钙调蛋白抑制剂作为活性成分的药物。该药物对抑制神经细胞死亡，特别是大脑神经细胞死亡，如脑缺血引起的神经细胞死亡具有益处。此外，还揭示了一种含有能够抑制钙调蛋白与细胞骨架蛋白结合的化合物作为活性成分的药物，以及一种含有抑制细胞骨架蛋白降解的化合物作为活性成分的药物。这些药物对治疗和预防大脑各种疾病及其后遗症，以及预防这些疾病的复发具有益处。

  公开号：

  US05661150A1

文献信息

• Piperazine derivatives
  申请人：Daiichi Pharmaceutical Co., Ltd.

  公开号：US05681954A1

  公开（公告）日：1997-10-28

  A compound represented by formula (I): ##STR1## wherein Q represents an aryl group, a heterocyclic group, a diarylmethyl group, an aralkyl group composed of an aryl group and an alkylene group, an alkyl group or a cycloalkyl group, in which the aryl group, heterocyclic group, and the aryl moiety of the diarylmethyl group and aralkyl group may be substituted with one or more substituents; R represents a bicyclic, substituted, nitrogen-containing heterocyclic group or a substituted phenyl group, in which the nitrogen-containing heterocyclic group is composed of a 5-membered, substituted, aromatic or saturated ring containing one or two nitrogen atoms and a 6-membered ring; and Z represents an alkylene group, an alkenylene group, an alkylene group, a carbonyl group, an alkylene group containing a carbonyl group or an oxalyl group, or a salt thereof. The compound has calmodulin inhibitory activity and is useful as a treating agent for diseases in the circulatory organs or in the cerebral region which are caused by excessive activation of calmodulin.

  一种由化学式(I)表示的化合物：##STR1## 其中Q代表芳基、杂环基、二芳基甲基基、芳基和烷基组成的芳基烷基基团、烷基或环烷基，其中芳基、杂环基、二芳基甲基基和芳基烷基基团中的芳基可被一个或多个取代基取代；R代表双环取代的含氮杂环基或取代的苯基，其中含氮杂环基由一个含有一个或两个氮原子的5元取代芳香或饱和环和一个6元环组成；Z代表烷基、烯烃基、烷基、羰基、含有羰基的烷基或草酸基，或其盐。该化合物具有钙调蛋白抑制活性，并可用作治疗因钙调蛋白过度活化引起的循环器官或脑区疾病的治疗剂。
• Piperazine derivatives useful as calmodolin inhibitors
  申请人：DAIICHI PHARMACEUTICAL CO., LTD.

  公开号：EP0624584A1

  公开（公告）日：1994-11-17

  A compound represented by formula (I): wherein Q represents an aryl group, a heterocyclic group, a diarylmethyl group, an aralkyl group composed of an aryl group and an alkylene group, an alkyl group or a cycloalkyl group, in which the aryl group, heterocyclic group, and the aryl moiety of the diarylmethyl group and aralkyl group may be substituted with one or more substituents; R represents a bicyclic, substituted, nitrogen-containing heterocyclic group or a substituted phenyl group, in which the nitrogen-containing heterocyclic group is composed of a 5-membered, substituted, aromatic or saturated ring containing one or two nitrogen atoms and a 6-membered ring; and Z represents an alkylene group, an alkenylene group, an alkylene group, a carbonyl group, an alkylene group containing a carbonyl group or an oxalyl group, or a salt thereof. The compound has calmodulin inhibitory activity and is useful as a treating agent for diseases in the circulatory organs or in the cerebral region which are caused by excessive activation of calmodulin.

  式 (I) 所代表的化合物： 其中 Q 代表芳基、杂环基、二芳甲基、由芳基和亚烷基组成的芳烷基、烷基或环 烷基，其中芳基、杂环基以及二芳甲基和芳烷基的芳基可被一个或多个取代基取代；R 代表双环、取代的含氮杂环基团或取代的苯基，其中含氮杂环基团由含有一个或两个氮原子的五元环、取代的芳香环或饱和环以及六元环组成；以及 Z 代表烯基、烯基、亚烷基、羰基、含有羰基的亚烷基或草酰基、 或其盐。该化合物具有钙调蛋白抑制活性，可用于治疗因钙调蛋白过度活化而引起的循环器官或脑部疾病。
• Use of calmodulin inhibitors for neuroprotection
  申请人：DAIICHI PHARMACEUTICAL CO., LTD.

  公开号：EP0627219A1

  公开（公告）日：1994-12-07

  A drug containing a calmodulin inhibitor as an active ingredient is disclosed. This drug is useful in the suppression of neuronal cell death, in particular brain neuronal cell death, due to, for example, cerebral ischemia. Also, a drug containing a compound capable of inhibiting binding of calmodulin to a cytoskeltal protein as an active ingredient and a drug containing a compound suppressing the breakdown of a cytoskeltal protein as an active ingredient are disclosed. These drugs are useful in the treatment and prevention of various diseases in the brain and sequelae thereof as well as in the prevention of relapses of these diseases.

  本研究公开了一种含有钙调蛋白抑制剂作为活性成分的药物。这种药物可用于抑制神经细胞死亡，特别是脑缺血等引起的脑神经细胞死亡。 此外，还公开了一种含有能够抑制钙调蛋白与细胞分裂蛋白结合的化合物作为活性成分的药物和一种含有抑制细胞分裂蛋白分解的化合物作为活性成分的药物。 这些药物可用于治疗和预防各种脑部疾病及其后遗症，以及预防这些疾病的复发。
• PIPERAZINE-CYCLODEXTRIN COMPLEXES
  申请人：DAIICHI PHARMACEUTICAL CO., LTD.

  公开号：EP1029872A1

  公开（公告）日：2000-08-23

  The present invention relates to a compound represented by formula (1): wherein Q, which may have a substituent, represents an aryl group, a heterocyclic group, a diarylmethyl group, or an aralkyl group; R, which may have a substituent, represents a bicyclic nitrogen-containing heterocyclic group or a phenyl group; and Z represents a C1-C3 alkylene group, a C2-C4 alkenylene group, a C1-C3 alkylene group having one hydroxyl group, a carbonyl moiety, a C1-C2 alkylene group containing one carbonyl moiety at one end or an intermediate position of the carbon chain, or an oxalyl group; or salts thereof and a piperazine-cyclodextrin complex combined with a water-soluble cyclodextrin derivative. The complex exhibits enhanced water solubility, excellent stability, and low topical stimulation and is useful as a therapeutic agent for circulatory diseases and diseases of the brain region.

  本发明涉及一种由式(1)表示的化合物： 其中 Q（可以有取代基）代表芳基、杂环基、二芳甲基或芳烷基；R（可以有取代基）代表双环含氮杂环基或苯基；Z 代表 C1-C3 亚烷基、C2-C4 烯基、具有一个羟基的 C1-C3 亚烷基、羰基、在碳链一端或中间位置含有一个羰基的 C1-C2 亚烷基或草酰基；或它们的盐以及与水溶性环糊精衍生物结合的哌嗪-环糊精复合物。 该复合物具有更强的水溶性、出色的稳定性和较低的局部刺激性，可用作循环系统疾病和脑部疾病的治疗剂。
• Piperazine derivatives useful as calmodulin inhibitors
  申请人：DAIICHI PHARMACEUTICAL CO., LTD.

  公开号：EP0624584B1

  公开（公告）日：1998-08-19