5-methoxy-1-{3-[4-(3-nitrophenyl)-1-piperazinyl]propyl}-3,4-dihydrocarbostyril | 145969-84-2

• 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: 5-methoxy-1-{3-[4-(3-nitrophenyl)-1-piperazinyl]propyl}-3,4-dihydrocarbostyril
• 英文别名: 5-Methoxy-1-[3-[4-(3-nitrophenyl)piperazin-1-yl]propyl]-3,4-dihydroquinolin-2-one
• CAS: 145969-84-2
• 化学式: C₂₃H₂₈N₄O₄
• 分子量: 424.5
• InChiKey: IPKDKVLEWIJDKE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  81.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-methoxy-1-{3-[4-(3-nitrophenyl)-1-piperazinyl]propyl}-3,4-dihydrocarbostyril 在 5percent Pd/C 氢气 作用下， 以 乙醇 为溶剂， 20.0 ℃ 、294.21 kPa 条件下， 以69%的产率得到1-{3-[4-(3-Aminophenyl)-1-piperazinyl]propyl}-5-methoxy-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
• 作为产物：
  描述：

  5-甲氧基-3,4-二氢-1H-喹啉-2-酮 在 sodium hydride 、 sodium carbonate 、 sodium iodide 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 11.0h， 生成 5-methoxy-1-{3-[4-(3-nitrophenyl)-1-piperazinyl]propyl}-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 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
• 5 HT RECEPTOR MEDIATED NEUROGENESIS
  申请人：Barlow Carrolee

  公开号：US20100009983A1

  公开（公告）日：2010-01-14

  The instant disclosure describes methods for treating diseases and conditions of the central and peripheral nervous system by stimulating or increasing neurogenesis. The disclosure includes compositions and methods based on use of a 5HTR agent, in combination with one or more other neurogenic agents, or anti-astrogenic agent, to stimulate or activate the formation of new nerve cells.
• 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.