3-(3-Chloropropyl)-7-(5-methyl-isoxazol-3-yl)-2,3,4,5-tetrahydro-1H-3-benzazepine | 427891-84-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: 3-(3-Chloropropyl)-7-(5-methyl-isoxazol-3-yl)-2,3,4,5-tetrahydro-1H-3-benzazepine
• 英文别名: 3-[3-(3-Chloropropyl)-1,2,4,5-tetrahydro-3-benzazepin-7-yl]-5-methyl-1,2-oxazole
• CAS: 427891-84-7
• 化学式: C₁₇H₂₁ClN₂O
• 分子量: 304.82
• InChiKey: PBGXNQFQOKBVDS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  29.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(3-Chloropropyl)-7-(5-methyl-isoxazol-3-yl)-2,3,4,5-tetrahydro-1H-3-benzazepine 、 4-甲基-5-吡啶-4-基-4H-[1,2,4]三唑-3-硫醇 在 sodium iodide potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 5-Methyl-3-[3-[3-[(4-methyl-5-pyridin-4-yl-1,2,4-triazol-3-yl)sulfanyl]propyl]-1,2,4,5-tetrahydro-3-benzazepin-7-yl]-1,2-oxazole
  参考文献：
  名称：

  1,2,4-Triazol-3-yl-thiopropyl-tetrahydrobenzazepines:  A Series of Potent and Selective Dopamine D₃ Receptor Antagonists

  摘要：

  The discovery of new highly potent and selective dopamine D-3 receptor antagonists has recently permitted characterization of the role of the dopamine D-3 receptor in a wide range, of preclinical animal models. A novel series of 1,2,4-triazol-3-yl-thiopropyl-tetrahydrobenzazepines demonstrating a high level of D3 affinity and selectivity with an excellent pharmacokinetic profile is reported here. In particular, the pyrazolyl derivative 35 showed good oral bioavailability and brain penetration associated with high potency and selectivity in vitro. In vivo characterization of 35 confirmed that this compound blocks the expression of nicotine- and cocaine-conditioned place preference in the rat, prevents nicotine-triggered reinstatement of nicotine- seeking behavior in the rat, reduces oral operant alcohol self- administration in the mouse, increases extracellular levels of acetylcholine in the rat medial prefrontal cortex, and potentiates the amplitude of the relative cerebral blood volume response to d-amphetamine in a regionally specific manner in the rat brain.

  DOI：

  10.1021/jm0705612
• 作为产物：
  描述：

  7-(5-methylisoxazol-3-yl)-2,3,4,5-tetrahydro-1H-3-benzazepine 、 1-溴-3-氯丙烷 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 3-(3-Chloropropyl)-7-(5-methyl-isoxazol-3-yl)-2,3,4,5-tetrahydro-1H-3-benzazepine
  参考文献：
  名称：

  1,2,4-Triazol-3-yl-thiopropyl-tetrahydrobenzazepines:  A Series of Potent and Selective Dopamine D₃ Receptor Antagonists

  摘要：

  The discovery of new highly potent and selective dopamine D-3 receptor antagonists has recently permitted characterization of the role of the dopamine D-3 receptor in a wide range, of preclinical animal models. A novel series of 1,2,4-triazol-3-yl-thiopropyl-tetrahydrobenzazepines demonstrating a high level of D3 affinity and selectivity with an excellent pharmacokinetic profile is reported here. In particular, the pyrazolyl derivative 35 showed good oral bioavailability and brain penetration associated with high potency and selectivity in vitro. In vivo characterization of 35 confirmed that this compound blocks the expression of nicotine- and cocaine-conditioned place preference in the rat, prevents nicotine-triggered reinstatement of nicotine- seeking behavior in the rat, reduces oral operant alcohol self- administration in the mouse, increases extracellular levels of acetylcholine in the rat medial prefrontal cortex, and potentiates the amplitude of the relative cerebral blood volume response to d-amphetamine in a regionally specific manner in the rat brain.

  DOI：

  10.1021/jm0705612

文献信息

• Tetrahydrobenzazepine derivatives useful as modulators of dopamine d3 receptors (antipsychotic agents)
  申请人：——

  公开号：US20040171606A1

  公开（公告）日：2004-09-02

  The invention provides compounds of formula (I): wherein: R 2 and R 3 independently represent various substituents; R 1 and R 4 independently represent H, F, Cl, Br, Cl 1-2 alkyl, C 1 alkoxy, OH, CN, or NO 2 ; B represents a sulfur atom or a —CH 2 -group; t represents 3 or 4; and A represents an optionally substituted 5- or 6-membered aromatic heterocyclic ring, or an optionally substituted bicyclic heterocyclic ring system in which at least the ring bound to the group B in Formula (I) is aromatic; or a salt thereof. Preferably, A is selected from one of the groups (i), (ii) or (iii): wherein X 1 and X 2 are independently N or CR 8 , and X 3 is NR 8 , O or S; Y 1 and Y 3 are independently N or CR 9 , and Y 2 is NR 9 , O or S; Z 1 is NR 10 , O or S, and Z 2 and Z 3 are independently N or CR 10 ; R 8 , R 9 , and R 10 are as herein defined, and R 7 is H, a halogen atom, OH, cyano, nitro, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkylenedioxy, C 1-4 alkanoyl, or C 1-4 alkylsulfonyl, an optionally substituted 3-, 4-, 5- or 6-membered cycloalkyl ring, or a group of the formula (a), (b), (c) or (d) as defined by the formulas (a), (b), (c) or (d). The compounds are modulators of dopamine D 3 receptors and have potential in the treatment of psychotic conditions (e.g. schizophrenia) or substance abuse.

  该发明提供了以下式（I）的化合物：其中：R2和R3分别代表各种取代基；R1和R4独立地代表H、F、Cl、Br、Cl1-2烷基、C1烷氧基、OH、CN或NO2；B代表硫原子或—CH2基团；t代表3或4；A代表一个可选择取代的5-或6-成员芳香杂环环，或者一个至少与式（I）中的基团B相结合的环是芳香的可选择取代的双环杂环环系统；或其盐。最好的情况是，A选自以下组之一：其中X1和X2独立地为N或CR8，X3为NR8、O或S；Y1和Y3独立地为N或CR9，Y2为NR9、O或S；Z1为NR10、O或S，Z2和Z3独立地为N或CR10；R8、R9和R10如上所定义，R7为H、卤素原子、OH、氰基、硝基、C1-4烷基、C1-4烷氧基、C1-4烷二氧基、C1-4烷酰基或C1-4烷基磺酰基，一个可选择取代的3-、4-、5-或6-成员环烷基环，或者由式（a）、（b）、（c）或（d）定义的式（a）、（b）、（c）或（d）的基团。这些化合物是多巴胺D3受体调节剂，对治疗精神病性疾病（如精神分裂症）或物质滥用具有潜在作用。
• TETRAHYDROBENZAZEPINE DERIVATIVES USEFUL AS MODULATORS OF DOPAMINE D3 RECEPTORS (ANTIPSYCHOTIC AGENTS)
  申请人：SMITHKLINE BEECHAM PLC

  公开号：EP1335915A2

  公开（公告）日：2003-08-20
• US7429579B2
  申请人：——

  公开号：US7429579B2

  公开（公告）日：2008-09-30
• [EN] TETRAHYDROBENZAZEPINE DERIVATIVES USEFUL AS MODULATORS OF DOPAMINE D3 RECEPTORS (ANTIPSYCHOTIC AGENTS)<br/>[FR] DERIVES DE TETRAHYDROBENZAZEPINE UTILES EN TANT QUE MODULATEURS DES RECEPTEURS D3 DE LA DOPAMINE (AGENTS ANTIPSYCHOTIQUES)
  申请人：SMITHKLINE BEECHAM PLC

  公开号：WO2002040471A2

  公开（公告）日：2002-05-23

  The invention provides compounds of formula (I), wherein R1-R4, A, B and t are as defined in claim 1. The compounds are modulators of dopamine D¿3? receptors and have potential in the treatment of psychotic conditions (e.g. schizophrenia) or substance abuse.
• 1,2,4-Triazol-3-yl-thiopropyl-tetrahydrobenzazepines:  A Series of Potent and Selective Dopamine D₃ Receptor Antagonists
  作者：Fabrizio Micheli、Giorgio Bonanomi、Frank E. Blaney、Simone Braggio、Anna Maria Capelli、Anna Checchia、Ornella Curcuruto、Federica Damiani、Romano Di Fabio、Daniele Donati、Gabriella Gentile、Andy Gribble、Dieter Hamprecht、Giovanna Tedesco、Silvia Terreni、Luca Tarsi、Andrew Lightfoot、Geoff Stemp、Gregor MacDonald、Alex Smith、Michela Pecoraro、Marcella Petrone、Ornella Perini、Jacqui Piner、Tino Rossi、Angela Worby、Maria Pilla、Enzo Valerio、Cristiana Griffante、Manolo Mugnaini、Martyn Wood、Claire Scott、Michela Andreoli、Laurent Lacroix、Adam Schwarz、Alessandro Gozzi、Angelo Bifone、Charles R. Ashby,、Jim J. Hagan、Christian Heidbreder

  DOI：10.1021/jm0705612

  日期：2007.10.1

  The discovery of new highly potent and selective dopamine D-3 receptor antagonists has recently permitted characterization of the role of the dopamine D-3 receptor in a wide range, of preclinical animal models. A novel series of 1,2,4-triazol-3-yl-thiopropyl-tetrahydrobenzazepines demonstrating a high level of D3 affinity and selectivity with an excellent pharmacokinetic profile is reported here. In particular, the pyrazolyl derivative 35 showed good oral bioavailability and brain penetration associated with high potency and selectivity in vitro. In vivo characterization of 35 confirmed that this compound blocks the expression of nicotine- and cocaine-conditioned place preference in the rat, prevents nicotine-triggered reinstatement of nicotine- seeking behavior in the rat, reduces oral operant alcohol self- administration in the mouse, increases extracellular levels of acetylcholine in the rat medial prefrontal cortex, and potentiates the amplitude of the relative cerebral blood volume response to d-amphetamine in a regionally specific manner in the rat brain.