1-(4-chloromethylbenzoyl)-4-methylpiperazine hydrochloride

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-(4-chloromethylbenzoyl)-4-methylpiperazine hydrochloride
• 英文别名: [4-(chloromethyl)phenyl]-(4-methylpiperazin-1-yl)methanone;hydrochloride
• 化学式: C₁₃H₁₇ClN₂O*ClH
• 分子量: 289.205
• InChiKey: JFKWJGUQQOQYHF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.23
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  23.6
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-[4-(4-hydroxybenzoyl)benzylthio]-3,5-dimethyl-4(3H)-quinazolinone 、 1-(4-chloromethylbenzoyl)-4-methylpiperazine hydrochloride 在 盐酸 、 potassium carbonate 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 生成 3,5-Dimethyl-2-[4-[4-[4-(4-methylpiperazinylcarbonyl)benzyloxy]benzoyl]benzylthio]-4(3H)-quinazolinone hydrochloride
  参考文献：
  名称：

  Heterocyclic compounds, their production and use

  摘要：

  一种新的化合物，其化学式为：A--Z--Ar.sup.1 1'CO--Ar.sup.2，其中A是一个紧凑的嘧啶酮或紧凑的吡啶并酮环；Ar.sup.1和Ar.sup.2分别是一个环；Z是一个二价基团，或其盐，具有出色的抗肿瘤活性。

  公开号：

  US05753664A1
• 作为产物：
  描述：

  N-甲基哌嗪 、 4-氯甲基苯甲酰氯 以 乙腈 为溶剂， 反应 2.0h， 以95%的产率得到1-(4-chloromethylbenzoyl)-4-methylpiperazine hydrochloride
  参考文献：
  名称：

  Synthesis and Pharmacological Evaluation of 5-(4-Biphenyl)-3-methyl-4-phenyl-1,2,4-triazole Derivatives as a Novel Class of Selective Antagonists for the Human Vasopressin V_1A Receptor

  摘要：

  A series of 5-(4-biphenyl)-3-methyl-4-phenyl-1,2,4-triazole derivatives were prepared and evaluated as selective antagonists for the human vasopressin VIA receptor. The compounds were examined for their affinity to the cloned human VIA receptor (hV(1A)) and selectivity vs the cloned human V-2 receptor (hV(2)). By utilizing the structure-activity relationship on 4,4-difluoro-5-methylidene-2,3,4,5-tetrahydrobenzazepine derivatives as dual antagonists for the VIA and V2 receptors in our previous study, we found that substituting the methoxy group at the 2-position of the 4-phenyl ring with (4-methylpiperazin-1-yl)alkoxy moieties brought about marked improvement of both affinity to hV1A and selectivity vs hV2. Further introduction of a methyl group into the 6-position of the 4-phenyl ring resulted in additional improvement of selectivity. One particular compound, 5-(4-biphenyl)-3-methyl-4-{2-[6-(4-methyl-1-piperazinyl)-hexyloxy]phenyl}-1,2,4-triazole (19) showed potent affinity to hV(1A) with a K-i value of 1.04 nM and high selectivity with a 1700-fold selectivity vs hV(2). We also found marked differences in the affinity of compounds in this series between the human and the rat receptors. Compound 19 was further examined for its VIA receptor antagonist activity in rats. As a result, 19 demonstrated antagonist activities toward an arginine vasopressin-induced increase in diastolic blood pressure after intravenous or oral administration and long-lasting oral activity.

  DOI：

  10.1021/jm010544r

文献信息

• US5753664A
  申请人：——

  公开号：US5753664A

  公开（公告）日：1998-05-19
• Heterocyclic compounds, their production and use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US05753664A1

  公开（公告）日：1998-05-19

  A novel compound of the formula: A--Z--Ar.sup.1 1'CO--Ar.sup.2 wherein A is a condensed pyrimidinone or condensed pyridazinone ring; Ar.sup.1 and Ar.sup.2 are independently a ring; Z is a divalent group, or a salt thereof which have an excellent antitumor activity.

  一种新的化合物，其化学式为：A--Z--Ar.sup.1 1'CO--Ar.sup.2，其中A是一个紧凑的嘧啶酮或紧凑的吡啶并酮环；Ar.sup.1和Ar.sup.2分别是一个环；Z是一个二价基团，或其盐，具有出色的抗肿瘤活性。
• Synthesis and Pharmacological Evaluation of 5-(4-Biphenyl)-3-methyl-4-phenyl-1,2,4-triazole Derivatives as a Novel Class of Selective Antagonists for the Human Vasopressin V_1A Receptor
  作者：Akio Kakefuda、Takeshi Suzuki、Takahiko Tobe、Junko Tsukada、Atsuo Tahara、Shuichi Sakamoto、Shin-ichi Tsukamoto

  DOI：10.1021/jm010544r

  日期：2002.6.1

  A series of 5-(4-biphenyl)-3-methyl-4-phenyl-1,2,4-triazole derivatives were prepared and evaluated as selective antagonists for the human vasopressin VIA receptor. The compounds were examined for their affinity to the cloned human VIA receptor (hV(1A)) and selectivity vs the cloned human V-2 receptor (hV(2)). By utilizing the structure-activity relationship on 4,4-difluoro-5-methylidene-2,3,4,5-tetrahydrobenzazepine derivatives as dual antagonists for the VIA and V2 receptors in our previous study, we found that substituting the methoxy group at the 2-position of the 4-phenyl ring with (4-methylpiperazin-1-yl)alkoxy moieties brought about marked improvement of both affinity to hV1A and selectivity vs hV2. Further introduction of a methyl group into the 6-position of the 4-phenyl ring resulted in additional improvement of selectivity. One particular compound, 5-(4-biphenyl)-3-methyl-4-2-[6-(4-methyl-1-piperazinyl)-hexyloxy]phenyl}-1,2,4-triazole (19) showed potent affinity to hV(1A) with a K-i value of 1.04 nM and high selectivity with a 1700-fold selectivity vs hV(2). We also found marked differences in the affinity of compounds in this series between the human and the rat receptors. Compound 19 was further examined for its VIA receptor antagonist activity in rats. As a result, 19 demonstrated antagonist activities toward an arginine vasopressin-induced increase in diastolic blood pressure after intravenous or oral administration and long-lasting oral activity.