1-{3-[4-(3-aminophenyl)-1-piperazinyl]propyl}-5-chloro-3,4-dihydrocarbostyril | 145969-63-7

• 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: 1-{3-[4-(3-aminophenyl)-1-piperazinyl]propyl}-5-chloro-3,4-dihydrocarbostyril
• 英文别名: 1-{3-[4-(3-Amino-phenyl)-piperazin-1-yl]-propyl}-5-chloro-3,4-dihydro-1H-quinolin-2-one；1-[3-[4-(3-aminophenyl)piperazin-1-yl]propyl]-5-chloro-3,4-dihydroquinolin-2-one
• CAS: 145969-63-7
• 化学式: C₂₂H₂₇ClN₄O
• 分子量: 398.936
• InChiKey: NSYVUZNCNUARQF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  52.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-{3-[4-(3-aminophenyl)-1-piperazinyl]propyl}-5-chloro-3,4-dihydrocarbostyril 在 4-二甲氨基吡啶 、 乙酸酐 作用下， 以 氯仿 为溶剂， 生成 1-{3-[4-(3-acetylaminophenyl)-1-piperazinyl]propyl}-5-chloro-3,4-dihydrocarbostyril hydrochloride
  参考文献：
  名称：

  Disturbance-of-consciousness improving agent

  摘要：

  本发明提供了一种改善意识障碍的药剂，这是一种高效且快速的药物疗法，可以口服给药。该发明的意识障碍改善剂含有σ受体激动剂化合物作为活性成分。

  公开号：

  US05556857A1
• 作为产物：
  描述：

  1-(3-硝基苯基)哌嗪 在 5percent Pd/C 氢气 、 sodium carbonate 作用下， 以 乙醇 、 乙腈 为溶剂， 生成 1-{3-[4-(3-aminophenyl)-1-piperazinyl]propyl}-5-chloro-3,4-dihydrocarbostyril
  参考文献：
  名称：

  3,4-Dihydro-2(1H)-quinolinone as a Novel Antidepressant Drug:  Synthesis and Pharmacology of 1-[3-[4-(3-Chlorophenyl)-1-piperazinyl]propyl]-3,4- dihydro-5-methoxy-2(1H)-quinolinone and Its Derivatives

  摘要：

  To develop a novel antidepressant drug with central nervous system-stimulating activity, me prepared a series of 1-[w-(4-substituted phenyl-1-piperazinyl)alkyl]-3,4-dihydro-2(1H)-quinlinone derivatives and examined their activities by their effects at 30 and 100 mg/kg po on the sleeping time of mice anesthetized with halothane and on the time required for recovery from coma induced in mice by cerebral concussion. We examined their binding affinities for a receptors by evaluating their ability to inhibit [H-3]-1,3-di(o-tolyl)guanidine ([H-3]DTG) binding to the rat whole brain membrane in comparison with three putative a receptor agonists: 1,3-di(o-tolyl)guanidine (DTG, 66), (+)-1,2,3,4,5,6-hexahydro-6,11-dimethylmethano-3-benzazecin-8-ol (SKF10,047, 67), and (+)-1,2,3,4,5,6-hexahydro-6, 11-dimethyl-3(3 -methyl-2-butenyl)-2,6-methano-3-benzazecin-8-ol (pentazocine, 68). Among the series of derivatives, 1-3-[4-(3-chlorophenyl)-1-piperazinyl]-3p linone hydrochloride (34b) and its mesylate (34c), at a dose of 30 mg/kg po, reduced the sleeping time and the time for recovery from coma and they inhibited [H-3]DTG binding for a receptors. The putative a receptor agonists reduced the sleeping time and the time for recovery from coma whereas two a receptor antagonists, alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl) piperazinebutanol hydrochloride (BMY14802, 69) and cis-9-[3-(3,5-dimethyl-1-piperazinyl)propyl]carbazole dihydrochloride (rimcazole, 70), were inactive in the two tests. Preadministration of the putative a receptor antagonists 69 (3 mg/kg po) and 70 (30 mg/kg po) completely antagonized the actions of 34b and the a receptor agonists in the test for recovery from coma. These results suggested that 34b and 34c are a receptor agonists. Furthermore, a single administration of 1 and 10 mg/kg po 34b and 34c showed antidepressant-like activity by reducing the immobility time in the forced-swimming test with mice, while a tricyclic antidepressant, 10,11-dihydro-N,N-dimethyl-5H-dibenz[b,f]azepine-5-propanamine hydrochloride (imipramine, 1) (10 and 30 mg/kg po), did not reduce the time after a single administration. 1 reduced the time after repeated administration of 30 mg/kg po once a day for 4 days. The structure-activity relationship of the series of compounds is also discussed.

  DOI：

  10.1021/jm980333v

文献信息

• Carbostyril derivatives and pharmaceutical compositions containing the
  申请人：Otsuka Pharmaceutical Co., Ltd.

  公开号：US05656633A1

  公开（公告）日：1997-08-12

  Disclosed is carbostyril derivatives of the general formula ##STR1## wherein R.sup.1 is a halogen, a hydroxyl, lower alkoxy, lower alkyl, lower alkenyloxy, amino, lower-alkanoyl amino or lower alkylthio group, R.sup.2 is a phenyl group which may optionally have one or two substituents, A is a lower alkylene group, and n is an integer of 1 or 2 and wherein the carbon-carbon bond between the positions 3 and 4 of the carbostyril skeleton may be a single bond or a double bond, and salts thereof, and pharmaceutical compositions containing the same for use as a disturbance-of-consciousness improving agent, central nervous system stimulant or sigma receptor agonist.

  本发明公开了一种通用式为 ##STR1## 的碳基苯基酮衍生物，其中R.sup.1是卤素、羟基、较低的烷氧基、较低的烷基、较低的烯基氧基、氨基、较低的烷酰胺基或较低的烷基硫基，R.sup.2是苯基，可以选择性地具有一个或两个取代基，A是较低的烷基烯基，n是1或2的整数，其中碳基苯基酮骨架的3和4位置之间的碳-碳键可以是单键或双键，以及其盐和含有它们的药物组合物，用作意识障碍改善剂、中枢神经系统兴奋剂或sigma受体激动剂。
• Carbostyril derivatives and pharmaceutical compositions containing the same for use as a disturbance-of-consciousness improving agent, central nervous system stimulant or sigma receptor agonist
  申请人：OTSUKA PHARMACEUTICAL CO., LTD.

  公开号：EP0512525B1

  公开（公告）日：1994-11-30
• US5556857A
  申请人：——

  公开号：US5556857A

  公开（公告）日：1996-09-17
• US5656633A
  申请人：——

  公开号：US5656633A

  公开（公告）日：1997-08-12
• 3,4-Dihydro-2(1<i>H</i>)-quinolinone as a Novel Antidepressant Drug:  Synthesis and Pharmacology of 1-[3-[4-(3-Chlorophenyl)-1-piperazinyl]propyl]-3,4- dihydro-5-methoxy-2(1<i>H</i>)-quinolinone and Its Derivatives
  作者：Yasuo Oshiro、Yoji Sakurai、Seiji Sato、Nobuyuki Kurahashi、Tatsuyoshi Tanaka、Tetsuro Kikuchi、Katsura Tottori、Yasufumi Uwahodo、Takashi Miwa、Takao Nishi

  DOI：10.1021/jm980333v

  日期：2000.1.1

  To develop a novel antidepressant drug with central nervous system-stimulating activity, me prepared a series of 1-[w-(4-substituted phenyl-1-piperazinyl)alkyl]-3,4-dihydro-2(1H)-quinlinone derivatives and examined their activities by their effects at 30 and 100 mg/kg po on the sleeping time of mice anesthetized with halothane and on the time required for recovery from coma induced in mice by cerebral concussion. We examined their binding affinities for a receptors by evaluating their ability to inhibit [H-3]-1,3-di(o-tolyl)guanidine ([H-3]DTG) binding to the rat whole brain membrane in comparison with three putative a receptor agonists: 1,3-di(o-tolyl)guanidine (DTG, 66), (+)-1,2,3,4,5,6-hexahydro-6,11-dimethylmethano-3-benzazecin-8-ol (SKF10,047, 67), and (+)-1,2,3,4,5,6-hexahydro-6, 11-dimethyl-3(3 -methyl-2-butenyl)-2,6-methano-3-benzazecin-8-ol (pentazocine, 68). Among the series of derivatives, 1-3-[4-(3-chlorophenyl)-1-piperazinyl]-3p linone hydrochloride (34b) and its mesylate (34c), at a dose of 30 mg/kg po, reduced the sleeping time and the time for recovery from coma and they inhibited [H-3]DTG binding for a receptors. The putative a receptor agonists reduced the sleeping time and the time for recovery from coma whereas two a receptor antagonists, alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl) piperazinebutanol hydrochloride (BMY14802, 69) and cis-9-[3-(3,5-dimethyl-1-piperazinyl)propyl]carbazole dihydrochloride (rimcazole, 70), were inactive in the two tests. Preadministration of the putative a receptor antagonists 69 (3 mg/kg po) and 70 (30 mg/kg po) completely antagonized the actions of 34b and the a receptor agonists in the test for recovery from coma. These results suggested that 34b and 34c are a receptor agonists. Furthermore, a single administration of 1 and 10 mg/kg po 34b and 34c showed antidepressant-like activity by reducing the immobility time in the forced-swimming test with mice, while a tricyclic antidepressant, 10,11-dihydro-N,N-dimethyl-5H-dibenz[b,f]azepine-5-propanamine hydrochloride (imipramine, 1) (10 and 30 mg/kg po), did not reduce the time after a single administration. 1 reduced the time after repeated administration of 30 mg/kg po once a day for 4 days. The structure-activity relationship of the series of compounds is also discussed.