5-((Phenylmethyl)methylamino)-5,6-dihydro-4H-imidazo(4,5,1-ij)quinoline-2(1H)-one | 132874-99-8

• 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-((Phenylmethyl)methylamino)-5,6-dihydro-4H-imidazo(4,5,1-ij)quinoline-2(1H)-one
• 英文别名: 5-((Phenylmethyl)methylamino)-5,6-dihydro-4H-imidazo(4,5,1-ij)quinolin-2(1H)-one；10-[benzyl(methyl)amino]-1,3-diazatricyclo[6.3.1.04,12]dodeca-4,6,8(12)-trien-2-one
• CAS: 132874-99-8
• 化学式: C₁₈H₁₉N₃O
• 分子量: 293.368
• InChiKey: GNBFGSNWNCGOJP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  35.6
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-((Phenylmethyl)methylamino)-5,6-dihydro-4H-imidazo(4,5,1-ij)quinoline-2(1H)-one 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 反应 18.0h， 生成 10-(Methylamino)-1,3-diazatricyclo[6.3.1.04,12]dodeca-4,6,8(12)-trien-2-one
  参考文献：
  名称：

  Synthesis and Biological Activities of (R)-5,6-Dihydro-N,N-dimethyl-4H-imidazo[4,5,1-ij]quinolin-5-amine and Its Metabolites

  摘要：

  The imidazoquinoline (R)-5,6-dihydro-N,N-dimethyl-4H-imidazo[(R)-3] is a potent dopamine agonist when tested in animals but surprisingly shows very low affinity in in vitro binding assays. When incubated with mouse or monkey liver S9 microsomes, (R)-3 is metabolized by N-demethylation and oxidation to (R)-5,6-dihydro-5-(methylamino)-4H-imidazo[4,5,1-ij]quinolin-2(lu)-one [(R)-6]; intermediate metabolites, where N-demethylation to the imidazoquinoline (R)-4 and where oxidation to the imidazoquinolinone (R)-5 has taken place, are also observed in these incubates. A cross-species study on the metabolism of (R)-3 in vitro has shown large variations in the extent of metabolism from species to species. Imidazoquinolinones (R)-5 and (R)-6 have comparable activity to (R)-3 in animals and also show good dopaminergic (D2) and serotonergic (5HT(1A)) activities in binding assays. It is probable that these metabolites account at least in part for the in vivo activity found for (R)-3. Efficient syntheses for compounds 3-6 as single enantiomers from quinoline are presented together with information on the biological activities and metabolic stabilities of these compounds.

  DOI：

  10.1021/jm960360q
• 作为产物：
  描述：

  (3S,4S)-3-Hydroxy-4-methylamino-3,4-dihydro-2H-quinoline-1-carboxylic acid tert-butyl ester 在 palladium on activated charcoal 对甲苯磺酰叠氮 、 potassium tert-butylate 、 氢气 、 仲丁基锂 、 sodium carbonate 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， -78.0~25.0 ℃ 、344.73 kPa 条件下， 反应 4.67h， 生成 5-((Phenylmethyl)methylamino)-5,6-dihydro-4H-imidazo(4,5,1-ij)quinoline-2(1H)-one
  参考文献：
  名称：

  Synthesis and Biological Activities of (R)-5,6-Dihydro-N,N-dimethyl-4H-imidazo[4,5,1-ij]quinolin-5-amine and Its Metabolites

  摘要：

  The imidazoquinoline (R)-5,6-dihydro-N,N-dimethyl-4H-imidazo[(R)-3] is a potent dopamine agonist when tested in animals but surprisingly shows very low affinity in in vitro binding assays. When incubated with mouse or monkey liver S9 microsomes, (R)-3 is metabolized by N-demethylation and oxidation to (R)-5,6-dihydro-5-(methylamino)-4H-imidazo[4,5,1-ij]quinolin-2(lu)-one [(R)-6]; intermediate metabolites, where N-demethylation to the imidazoquinoline (R)-4 and where oxidation to the imidazoquinolinone (R)-5 has taken place, are also observed in these incubates. A cross-species study on the metabolism of (R)-3 in vitro has shown large variations in the extent of metabolism from species to species. Imidazoquinolinones (R)-5 and (R)-6 have comparable activity to (R)-3 in animals and also show good dopaminergic (D2) and serotonergic (5HT(1A)) activities in binding assays. It is probable that these metabolites account at least in part for the in vivo activity found for (R)-3. Efficient syntheses for compounds 3-6 as single enantiomers from quinoline are presented together with information on the biological activities and metabolic stabilities of these compounds.

  DOI：

  10.1021/jm960360q

文献信息

• Heterocyclic amines having central nervous system activity
  申请人：The Upjohn Company

  公开号：US05273975A1

  公开（公告）日：1993-12-28

  Tricyclic nitrogen containing compounds, having central nervous system activity of the following structural formula: ##STR1## and pharmaceutically acceptable salts thereof wherein R.sub.1, R.sub.2, and R.sub.3 are independently hydrogen, C.sub.1-6 alkyl, alkenyl, or alkynyl, C.sub.3-10 cycloalkyl, or R.sub.1 and R.sub.2 are joined to form a C.sub.3-7 cyclic amine which can contain additional heteroatoms; X is hydrogen, C.sub.1-6 alkyl halogen, hydroxy, alkoxy, cyano, carboxamide, carboxyl, or carboalkoxyl; A is SO.sub.2, N, CH, CH.sub.2, CHCH.sub.3, C.dbd.O, C.dbd.S, C-SCH.sub.3, C.dbd.NH, C-NH.sub.2, C-NHCH.sub.3, C--NHCOOCH.sub.3, or C--NHCN. B is CH.sub.2, CH, C.dbd.O, N, NH or N--CH.sub.3 ; n is 0 or 1; and D is CH, CH.sub.2, C.dbd.O, O, N, NH or N--CH.sub.3. These new compounds are suitable for treating schizophrenia, Parkinson's disease, anxiety, depression or as compounds for lowering blood pressure in animal or human hosts.

  三环氮含化合物，具有以下结构式的中枢神经系统活性：##STR1##及其药学上可接受的盐，其中R.sub.1、R.sub.2和R.sub.3独立地是氢、C.sub.1-6烷基、烯基或炔基、C.sub.3-10环烷基，或R.sub.1和R.sub.2连接形成可含有额外杂原子的C.sub.3-7环胺；X是氢、C.sub.1-6烷基卤素、羟基、烷氧基、氰基、羧酰胺、羧基或羧烷氧基；A是SO.sub.2、N、CH、CH.sub.2、CHCH.sub.3、C.dbd.O、C.dbd.S、C-SCH.sub.3、C.dbd.NH、C-NH.sub.2、C-NHCH.sub.3、C--NHCOOCH.sub.3或C--NHCN。B是CH.sub.2、CH、C.dbd.O、N、NH或N--CH.sub.3；n为0或1；D是CH、CH.sub.2、C.dbd.O、O、N、NH或N--CH.sub.3。这些新化合物适用于治疗精神分裂症、帕金森病、焦虑、抑郁或作为降低动物或人类宿主血压的化合物。
• HETEROCYCLIC AMINES HAVING CENTRAL NERVOUS SYSTEM ACTIVITY
  申请人：THE UPJOHN COMPANY

  公开号：EP0480939B1

  公开（公告）日：1995-01-25
• US5273975A
  申请人：——

  公开号：US5273975A

  公开（公告）日：1993-12-28
• US5436240A
  申请人：——

  公开号：US5436240A

  公开（公告）日：1995-07-25
• Synthesis and Biological Activities of (<i>R</i>)-5,6-Dihydro-<i>N</i>,<i>N</i>-dimethyl-4<i>H</i>-imidazo[4,5,1-<i>ij</i>]quinolin-5-amine and Its Metabolites
  作者：Richard F. Heier、Lester A. Dolak、J. Neil Duncan、Deborah K. Hyslop、Michael F. Lipton、Iain J. Martin、Michael A. Mauragis、Montford F. Piercey、Nanette F. Nichols、Peggy J. K. D. Schreur、Martin W. Smith、Malcolm W. Moon

  DOI：10.1021/jm960360q

  日期：1997.2.1

  The imidazoquinoline (R)-5,6-dihydro-N,N-dimethyl-4H-imidazo[(R)-3] is a potent dopamine agonist when tested in animals but surprisingly shows very low affinity in in vitro binding assays. When incubated with mouse or monkey liver S9 microsomes, (R)-3 is metabolized by N-demethylation and oxidation to (R)-5,6-dihydro-5-(methylamino)-4H-imidazo[4,5,1-ij]quinolin-2(lu)-one [(R)-6]; intermediate metabolites, where N-demethylation to the imidazoquinoline (R)-4 and where oxidation to the imidazoquinolinone (R)-5 has taken place, are also observed in these incubates. A cross-species study on the metabolism of (R)-3 in vitro has shown large variations in the extent of metabolism from species to species. Imidazoquinolinones (R)-5 and (R)-6 have comparable activity to (R)-3 in animals and also show good dopaminergic (D2) and serotonergic (5HT(1A)) activities in binding assays. It is probable that these metabolites account at least in part for the in vivo activity found for (R)-3. Efficient syntheses for compounds 3-6 as single enantiomers from quinoline are presented together with information on the biological activities and metabolic stabilities of these compounds.