N-(2,3,6,7-tetrahydro-3-oxo-1H,5H-benzoquinolizin-2-yl)propanamide | 132874-13-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-(2,3,6,7-tetrahydro-3-oxo-1H,5H-benzoquinolizin-2-yl)propanamide
• 英文别名: N-(2,3,6,7-Tetrahydro-3-oxo-1H,5H-benzo(ij)quinolizin-2-yl)-propanamide；N-(2-oxo-1-azatricyclo[7.3.1.05,13]trideca-5,7,9(13)-trien-3-yl)propanamide
• CAS: 132874-13-6
• 化学式: C₁₅H₁₈N₂O₂
• 分子量: 258.32
• InChiKey: BJAASNVUEKMURU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  49.4
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-(2,3,6,7-tetrahydro-3-oxo-1H,5H-benzoquinolizin-2-yl)propanamide 在 lithium aluminium tetrahydride 、 potassium carbonate 作用下， 以 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.0h， 生成 2,3,6,7-tetrahydro-N,N-dipropyl-1H,5H-benzoquinolizin-2-amine
  参考文献：
  名称：

  Dopaminergic and serotonergic activities of imidazoquinolinones and related compounds

  摘要：

  The synthesis of 5-(dipropylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2(1H)-one (5), a potent dopamine D2 agonist showing high dopamine/serotonin (5HT1A) selectivity, is described. Dopaminergic activity is associated with the (R)-enantiomer of 5; the (S)-enantiomer shows no dopaminergic activity. A series of analogues where the imidazolone ring was modified to various 5- or 6-membered heterocyclic rings were prepared. Some of these compounds showed a combination of dopaminergic and serotonergic activity, while one compound, 6-(dipropylamino)-1,2,6,7-tetrahydro-3H,5H-pyrido[3,2,1-ij]quinazolin-3-one (24), was a selective serotonergic agonist. Various analogues of 5 where the dipropylamine substituent was modified were prepared. Most of these showed reduced dopaminergic activity, while several were as potent as 5 at the serotonin 5HT1A receptor. Orientations for the new compounds at dopamine and serotonin receptors are proposed and compared with those of other tricyclic ligands known to have high affinity at these receptors.

  DOI：

  10.1021/jm00084a013
• 作为产物：
  描述：

  8-溴甲基喹啉 在 platinum(IV) oxide sodium hydroxide 、 氢气 、 sodium ethanolate 、 溶剂黄146 作用下， 以 甲醇 、 乙醇 为溶剂， 25.0 ℃ 、344.73 kPa 条件下， 反应 1.16h， 生成 N-(2,3,6,7-tetrahydro-3-oxo-1H,5H-benzoquinolizin-2-yl)propanamide
  参考文献：
  名称：

  Dopaminergic and serotonergic activities of imidazoquinolinones and related compounds

  摘要：

  The synthesis of 5-(dipropylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2(1H)-one (5), a potent dopamine D2 agonist showing high dopamine/serotonin (5HT1A) selectivity, is described. Dopaminergic activity is associated with the (R)-enantiomer of 5; the (S)-enantiomer shows no dopaminergic activity. A series of analogues where the imidazolone ring was modified to various 5- or 6-membered heterocyclic rings were prepared. Some of these compounds showed a combination of dopaminergic and serotonergic activity, while one compound, 6-(dipropylamino)-1,2,6,7-tetrahydro-3H,5H-pyrido[3,2,1-ij]quinazolin-3-one (24), was a selective serotonergic agonist. Various analogues of 5 where the dipropylamine substituent was modified were prepared. Most of these showed reduced dopaminergic activity, while several were as potent as 5 at the serotonin 5HT1A receptor. Orientations for the new compounds at dopamine and serotonin receptors are proposed and compared with those of other tricyclic ligands known to have high affinity at these receptors.

  DOI：

  10.1021/jm00084a013

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
• [EN] HETEROCYCLIC AMINES HAVING CENTRAL NERVOUS SYSTEM ACTIVITY
  申请人：THE UPJOHN COMPANY

  公开号：WO1990015058A1

  公开（公告）日：1990-12-13

  (EN) Tricyclic nitrogen containing compounds, having central nervous system activity of structural formula (I) and pharmaceutically acceptable salts thereof, wherein R1, R2, and R3 are independently hydrogen, C1-6 alkyl, alkenyl, or alkynyl, C3-10 cycloalkyl, or R1 and R2 are joined to form a C3-7 cyclic amine which can contain additional heteroatoms; X is hydrogen, C1-6 alkyl, halogen, hydroxy, alkoxy, cyano, carboxamide, carboxyl, or carboalkoxyl; A is SO2, N, CH, CH2, CHCH3, C=O, C=S, C-SCH3, C=NH, C-NH2, C-NHCH3, C-NHCOOCH3, or C-NHCN; B is CH2, CH, C=O, N, NH or N-CH3; n is 0 or 1; and D is CH, CH2, C=O, O, N, NH or N-CH3. 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.(FR) De l'azote tricyclique comprenant des composés agissant sur le système nerveux central et correspondant à la formule de structure (I), et leur sels acceptables en pharmaceutique, où R1, R2 et R3 sont indépendamment l'hydrogène, un alkyle C1-6, un alkényle, ou un alkynyle, un cycloalkyle C3-10, ou bien R1 et R2 sont liés et forment une amine cyclique C3-7 qui peut contenir des hétéroatomes supplémentaires; X est l'hydrogène, un alkyle C1-6, l'halogène, l'hydroxy, l'alkoxy, le cyano, le carboxamide, le carboxyle, ou carboalkoxyle; A est SO2, N, CH, CH2, CHCH3, C=O, C=S, C-SCH3, C=NH, C-NH2, C-NHCH3, C-NHCOOCH3, ou C-NHCN; B est CH2, CH, C=O, N, NH, ou N-CH3; n est 0 ou 1; et D est CH, CH2, C=O, O, N, NH ou N-CH3. Lesdits composés sont utilisables dans le traitement de la schizophrénie, de la maladie de Parkinson, de l'anxiété, de la dépression ou, en tant que composés, pour abaisser la tension artérielle dans des hôtes humains ou animaux.