4-<4-(4-fluorophenyl)-1-piperazinyl>butyric acid | 130933-46-9

• 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: 4-<4-(4-fluorophenyl)-1-piperazinyl>butyric acid
• 英文别名: 4-[4-(4-Fluorophenyl)piperazin-1-ium-1-yl]butanoate
• CAS: 130933-46-9
• 化学式: C₁₄H₁₉FN₂O₂
• mdl: MFCD09707467
• 分子量: 266.315
• InChiKey: GANNFTQFVSIZSZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  43.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-<4-(4-fluorophenyl)-1-piperazinyl>butyric acid 在 sodium periodate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 2.0h， 生成 (6aR^*,10aR^*,11R^*)-11-<<4-<4-(4-fluorophenyl)-1-piperazinyl>butyryl>amino>-6,6a,7,8,9,10,10a,11-octahydrodibenzothiepin 5-oxide
  参考文献：
  名称：

  A new class of calcium antagonists. Synthesis and biological activity of 11-[(.omega.-aminoalkanoyl)amino]-6,6a,7,8,9,10,10a,11-octahydrodibenzo[b,e]thiepin derivatives

  摘要：

  A series of 11-[(omega-aminoalkanoyl)amino]-6,6a,7,8,9,10,10a,11?? -octahydrodibenzo[b,e]thiepin derivatives were prepared and found to be a structurally new class of calcium antagonists. The structure-activity relationship studies indicated that the optimum was (6aR*, 10aR*, 11R*)-11-[[4-[4-(4-fluorophenyl)-1-piperazinyl]butyryl]amino]-6,6a7,8,9,10,10a,11-octahydrodibenzo[b,e]thiepin (31, pA2 8.16), which was superior to diltiazem (pA2 7.42) in calcium antagonistic activity. Compound 31 showed antihypertensive activity in anesthetized rats, without a significant effect on the heart rate. It had also antianginal effects in vasopressin-induced ST-depression and methacholine-induced ST-elevation testings in rats. These potencies of 31 were essentially equal to those of diltiazem.

  DOI：

  10.1021/jm00106a019
• 作为产物：
  描述：

  ethyl 4-<4-(4-fluorophenyl)-1-piperazinyl>butyrate 在 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 生成 4-<4-(4-fluorophenyl)-1-piperazinyl>butyric acid
  参考文献：
  名称：

  作为5-HT7受体配体的新型喹唑啉酮衍生物。

  摘要：

  5-HT（7）受体拮抗剂在动物模型中产生了抗抑郁样作用，并且5-HT（7）受体参与了其他病理生理机制，例如温度调节，学习和记忆以及睡眠，这一点已被各种研究重点介绍。作为我们发现新型5-HT（7）受体拮抗剂的工作之一，我们在此报告喹唑啉酮文库1的5-HT（7）受体的合成和结合亲和力，该库设计有各种取代基（X，Y，R（1）和R（2））在芳香环上和不同的碳链长度。合成了喹唑啉酮文库1的总共85种化合物，并通过放射性配体结合测定法对5-HT（7）受体获得了所有合成化合物的结合亲和力。在85种化合物中，24种化合物显示出非常好的结合亲和力，IC（50）值低于100 nM。IC（50）值低于100 nM的化合物主要具有o-OMe或o-OEt作为R（2）取代基。具有最佳结合亲和力的化合物为1-68，其中IC（50）值为12 nM。在体内动物研究中，某些合成的化合物在小鼠的强迫游泳试验中确实具有抗抑郁活性。

  DOI：

  10.1016/j.bmc.2007.11.049

文献信息

• Calcium antagonist piperazine derivatives, and compositions therefor
  申请人：Dainippon Pharmaceutical Co., Ltd.

  公开号：US04749703A1

  公开（公告）日：1988-06-07

  Compounds of the formula: ##STR1## wherein A means an alkylene; Y--Z means ##STR2## --CH.dbd.CH--, --CH.sub.2 CH.sub.2 --, or ##STR3## R.sub.1 and R.sub.2 are each a substituent; R.sub.3 is hydrogen atom, alkyl, or alkoxy; R.sub.4 is phenyl, phenylalkyl, phenylalkenyl, diphenylmethyl, naphthyl, thiazolyl, optionally substituted pyridyl, optionally substituted pyrimidinyl, quinolyl, benzoylalkyl, benzoyl, furoyl, thenoyl, phenyloxycarbonyl, phenyloxysulfonyl, or phenylsulfonyl; a is 2 or 3, b and c are each 1 or 2, and d is an integer of 0 to 2, provided that the phenyl, phenyl moiety and naphthyl may optionally be substituted, and a pharmaceutically acceptable salt thereof, process for the preparation thereof, and pharmaceutical composition containing the same. The compounds and salt thereof show potent calcium antagonistic activity and are useful for prophylaxis and treatment of hypertension and/or ischemic heart disease.

  化合物的式子：##STR1## 其中，A表示烷基；Y--Z表示##STR2## --CH.dbd.CH--, --CH.sub.2 CH.sub.2 --,或##STR3## R.sub.1和R.sub.2是每个取代基；R.sub.3是氢原子、烷基或烷氧基；R.sub.4是苯基、苯基烷基、苯基烯基、二苯甲基、萘基、噻唑基、可选取代的吡啶基、可选取代的嘧啶基、喹啉基、苯甲酰基烷基、苯甲酰基、呋喃基、硫代苯甲酰基、苯氧羰基、苯氧基磺酰基或苯基磺酰基；a为2或3，b和c分别为1或2，d为0到2之间的整数，但苯基、苯基基团和萘基可选择性地被取代，以及其药学上可接受的盐、制备方法和包含其的药物组合物。这些化合物和它们的盐表现出强大的钙拮抗作用，并且用于预防和治疗高血压和/或缺血性心脏病。
• TRYCICLIC OR TETRACYCLIC COMPOUNDS, PROCESS FOR THEIR PREPARATION, AND MEDICINAL COMPOSITION CONTAINING THEM
  申请人：Dainippon Pharmaceutical Co., Ltd.

  公开号：EP0191867B1

  公开（公告）日：1991-10-16
• KUROKAWA, MIKIO;SATO, FUMINORI;HATANO, NAONOBU;HONDA, YAYOI;UNO, HITOSHI, J. MED. CHEM. , 34,(1991) N, C. 593-599
  作者：KUROKAWA, MIKIO、SATO, FUMINORI、HATANO, NAONOBU、HONDA, YAYOI、UNO, HITOSHI

  DOI：——

  日期：——
• US4749703A
  申请人：——

  公开号：US4749703A

  公开（公告）日：1988-06-07
• A new class of calcium antagonists. Synthesis and biological activity of 11-[(.omega.-aminoalkanoyl)amino]-6,6a,7,8,9,10,10a,11-octahydrodibenzo[b,e]thiepin derivatives
  作者：Mikio Kurokawa、Fuminori Sato、Naonobu Hatano、Yayoi Honda、Hitoshi Uno

  DOI：10.1021/jm00106a019

  日期：1991.2

  A series of 11-[(omega-aminoalkanoyl)amino]-6,6a,7,8,9,10,10a,11?? -octahydrodibenzo[b,e]thiepin derivatives were prepared and found to be a structurally new class of calcium antagonists. The structure-activity relationship studies indicated that the optimum was (6aR*, 10aR*, 11R*)-11-[[4-[4-(4-fluorophenyl)-1-piperazinyl]butyryl]amino]-6,6a7,8,9,10,10a,11-octahydrodibenzo[b,e]thiepin (31, pA2 8.16), which was superior to diltiazem (pA2 7.42) in calcium antagonistic activity. Compound 31 showed antihypertensive activity in anesthetized rats, without a significant effect on the heart rate. It had also antianginal effects in vasopressin-induced ST-depression and methacholine-induced ST-elevation testings in rats. These potencies of 31 were essentially equal to those of diltiazem.