5-benzylideneamino-1-(3-chloropropyl)-3,4-dihydro-2(1H)-quinolinone | 260369-81-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 5-benzylideneamino-1-(3-chloropropyl)-3,4-dihydro-2(1H)-quinolinone
• 英文别名: 5-(Benzylideneamino)-1-(3-chloropropyl)-3,4-dihydroquinolin-2-one
• CAS: 260369-81-1
• 化学式: C₁₉H₁₉ClN₂O
• 分子量: 326.826
• InChiKey: RCUOZISFRFXIGC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  32.7
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-benzylideneamino-1-(3-chloropropyl)-3,4-dihydro-2(1H)-quinolinone 在 盐酸 、 三乙胺 、 sodium iodide 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 1.0h， 生成 5-amino-1-[3-[4-(3-chlorophenyl)-1-piperazinyl]propyl]-3,4-dihydro-2(1H)-quinolinone dihydrochloride
  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-氨基-3,4-二氢-2(1H)-喹啉酮 在 sodium hydride 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 5-benzylideneamino-1-(3-chloropropyl)-3,4-dihydro-2(1H)-quinolinone
  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

• 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.