4-butyl-N-(2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)benzenesulfonamide | 583025-17-6

• 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: 4-butyl-N-(2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)benzenesulfonamide
• CAS: 583025-17-6
• 化学式: C₂₀H₂₆N₂O₂S
• 分子量: 358.505
• InChiKey: DFONPZSBELPUSI-UHFFFAOYSA-N

物化性质

• 沸点：
  519.4±60.0 °C(Predicted)
• 密度：
  1.175±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  66.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-butyl-N-(2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)benzenesulfonamide 、 1H-吡唑-3-甲醛 在 MP-BH(OAc)3 resin 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-(3-((1H-pyrazol-3-yl)methyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yl)-4-butylbenzenesulfonamide
  参考文献：
  名称：

  The discovery and optimisation of benzazepine sulfonamide and sulfones as potent agonists of the motilin receptor

  摘要：

  Optimisation of a series of benzazepine sulfonamide hit compounds identified from high throughput screening led to the discovery of a new series of tractable, potent motilin receptor agonists. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.09.027
• 作为产物：
  描述：

  3-BOC-7-氨基-1,2,4,5-四氢苯并[D]氮杂卓 在 吡啶 、 盐酸 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 14.0h， 生成 4-butyl-N-(2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)benzenesulfonamide
  参考文献：
  名称：

  Studies towards the identification of a new generation of atypical antipsychotic agents

  摘要：

  A rational structure-activity relationship study around compound (1) is reported. The lead optimisation programme led to the identification of sulfonamide (25), a molecule combining dopamine D-2/D-3 receptor antagonism with serotonin 5-HT2A, 5-HT2C, 5-HT6 receptor antagonism for an effective treatment of schizophrenia. Compound (25) was shown to possess the required in vivo activity with no EPS liability. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.10.036

文献信息

• Benzenesulfonamide derivatives
  申请人：Cooper G David

  公开号：US20050085461A1

  公开（公告）日：2005-04-21

  The invention provides compounds of formula (I) wherein A and B represent the groups CH 2 ) m — and CH 2 ) n — respectively; R 1 represents hydrogen or C 1-4 alkyl; R 2 represents hydrogen, halogen, hydroxy, cyano, nitro, hydroxyC 1-6 alkyl, trifluoromethyl, trifluoromethoxy, C 1-6 alkyl, C 1-6 alkoxy, —(CH 2 ) p C 3-6 cycloalkyl, —(CH 2 ) p C 3-6 cycloalkyloxy, —COC 1-6 alkyl, —SO 2 C 1-6 alkyl, —SOC 1-6 alkyl, —S-C 1-6 alkyl, —CO 2 C 1-6 alkyl, —CO 2 NR 7 R 8 , —SO 2 NR 7 R 8 , —(CH 2 ) p NR 7 R 8 , —(CH 2 ) p NR 7 COR 8 , optionally substituted aryl, optionally substituted heteroaryl or a fused bicyclic heterocyclic ring system; R 3 represents hydrogen or C 1-6 alkyl; R 4 represents halogen, trifluoromethyl, trifluoromethoxy, C 1-6 alkyl, C 1-6 alkoxy, —(CH 2 ) p C 3-6 cycloalkyl or —(CH 2 ) p C 3-6 cycloalkyloxy; R 5 and R 6 each independently represent hydrogen, halogen, hydroxy, cyano, nitro, hydroxyC 1-6 alkyl, trifluoromethyl, trifluoromethoxy, C 1-6 alkyl, C 1-6 alkoxy, —(CH 2 ) p C 3-6 cycloalkyl, —(CH 2 ) p C 3-6 cycloalkyloxy, —COC 1-6 alkyl, —SO 2 C 1-6 alkyl, —SOC 1-6 alkyl, —S—C 1-6 alkyl, —CO 2 C 1-6 alkyl, —CO 2 NR 7 R 8 , —SO 2 NR 7 R 8 , —(CH 2 ) p NR 7 R 8 , —(CH 2 ) p NR 7 COR 8 , optionally substituted aryl, optionally substituted heteroaryl or a fused bicyclic heterocyclic ring system; R 7 and R 8 each independently represent hydrogen or C 1-6 alkyl; m and n independently represent an integer selected from 1 and 2; p independently represents an integer selected from 0, 1, 2 and 3; or a pharmaceutically acceptable salt or solvate thereof, with the proviso that the compounds 4-methyl-N-(1,2,3,4-tetrahydroisoquinolin-6-yl)-benzenesulfonamide, 7-(4-chlorophenyl)sulfonamido-1,2,3,4-tetrahydroisoquinoline hydrochloride and N-(2-ethyl-5-isoindolinyl)-p-toluenesulfonamide are excluded. The compounds are useful in therapy, in particular as antipsychotic agents.

  该发明提供了式（I）的化合物，其中A和B分别代表基团CH2）m-和CH2）n-; R1代表氢或C1-4烷基; R2代表氢，卤素，羟基，氰基，硝基，羟基C1-6烷基，三氟甲基，三氟甲氧基，C1-6烷基，C1-6烷氧基， -（CH2）pC3-6环烷基， -（CH2）pC3-6环烷氧基， -COC1-6烷基， -SO2C1-6烷基， -SOC1-6烷基， -S-C1-6烷基， -CO2C1-6烷基， -CO2NR7R8， -SO2NR7R8， -（CH2）pNR7R8， -（CH2）pNR7COR8，可选地取代的芳基，可选地取代的杂环芳基或融合的双环杂环环系; R3代表氢或C1-6烷基; R4代表卤素，三氟甲基，三氟甲氧基，C1-6烷基，C1-6烷氧基， -（CH2）pC3-6环烷基或 -（CH2）pC3-6环烷氧基; R5和R6各自独立地代表氢，卤素，羟基，氰基，硝基，羟基C1-6烷基，三氟甲基，三氟甲氧基，C1-6烷基，C1-6烷氧基， -（CH2）pC3-6环烷基， -（CH2）pC3-6环烷氧基， -COC1-6烷基， -SO2C1-6烷基， -SOC1-6烷基， -S-C1-6烷基， -CO2C1-6烷基， -CO2NR7R8， -SO2NR7R8， -（CH2）pNR7R8， -（CH2）pNR7COR8，可选地取代的芳基，可选地取代的杂环芳基或融合的双环杂环环系; R7和R8各自独立地代表氢或C1-6烷基; m和n各自独立地代表选自1和2的整数; p独立地代表选自0、1、2和3的整数; 或其药学上可接受的盐或溶剂，但不包括4-甲基-N-（1,2,3,4-四氢异喹啉-6-基）-苯磺酰胺，7-（4-氯苯基）磺酰胺-1,2,3,4-四氢异喹啉盐酸盐和N-（2-乙基-5-异吲哚基）-对甲苯磺酰胺。该化合物在治疗中有用，特别是作为抗精神病药物。
• BENZENESULFONAMIDE DERIVATIVES AND THEIR USE AS DOPAMINE D3 AND D2 RECEPTOR LIGANDS
  申请人：GLAXO GROUP LIMITED

  公开号：EP1495004A2

  公开（公告）日：2005-01-12
• [EN] BENZENESULFONAMIDE DERIVATIVES<br/>[FR] DERIVES BENZENESULFONAMIDE
  申请人：GLAXO GROUP LTD

  公开号：WO2003068732A2

  公开（公告）日：2003-08-21

  The invention provides compounds of formula (I) wherein A and B represent the groups -(CH2)m- and -(CH2)n- respectively; R1 represents hydrogen or C1-6alkyl; R2 represents hydrogen, halogen, hydroxy, cyano, nitro, hydroxyC1-6alkyl, trifluoromethyl, trifluoromethoxy, C1-6alkyl, C1-6alkoxy, -(CH2)pC3-6cycloalkyl, -(CH2)pC3-6cycloalkyloxy, -COC1-6alkyl, -SOC1-6alkyl, -SOC1-6alkyl, -S-C1-6alkyl, -COC1-6alkyl, -CO2NR7R8, -SO2NR7R8, -(CH2)pNR7R8, -(CH2)pNR7COR8, optionally substituted aryl, optionally substituted heteroaryl or a fused bicyclic heterocyclic ring system; R3 represents hydrogen or C1-6alkyl; R4 represents halogen, trifluoromethyl, trifluoromethoxy, C1-6alkyl, C1-6alkoxy, -(CH2)pC3-6cycloalkyl or -(CH2)pC3-6cycloalkyloxy; R5 and R6 each independently represent hydrogen, halogen, hydroxy, cyano, nitro, hydroxyC1-6alkyl, trifluoromethyl, trifluoromethoxy, C1-6alkyl, C1-6alkoxy, -(CH2)pC3-6cycloalkyl, -(CH2)pC3-6cycloalkyloxy, -COC1-6alkyl, -SO2C1-6alkyl, -SOC1-6alkyl, -S-C1-6alkyl, -CO2C1-6alkyl, -CO2NR7R8, -SO2NR7R8, -(CH2)pNR7R8, -(CH2)pNR7COR8, optionally substituted aryl, optionally substituted heteroaryl or a fused bicyclic heterocyclic ring system; R7 and R8 each independently represent hydrogen or C1-6alkyl;m and n independently represent an integer selected from 1 and 2;p independently represents an integer selected from 0, 1, 2 and 3; or a pharmaceutically acceptable salt or solvate thereof,with the proviso that the compounds 4-methyl-N-(1,2,3,4-tetrahydroisoquinolin-6-yl)-benzenesulfonamide, 7-(4-chlorophenyl)sulfonamido-1,2,3,4-tetrahydroisoquinoline hydrochloride and N-(2-ethyl-5-isoindolinyl)-p-toluenesulfonamide are excluded.The compounds are useful in therapy, in particular as antipsychotic agents.
• Studies towards the identification of a new generation of atypical antipsychotic agents
  作者：Vincenzo Garzya、Ian T. Forbes、Andrew D. Gribble、Mike S. Hadley、Andrew P. Lightfoot、Andrew H. Payne、Alexander B. Smith、Sara E. Douglas、David G. Cooper、Ian G. Stansfield、Malcom Meeson、Emma E. Dodds、Declan N.C. Jones、Martyn Wood、Charlie Reavill、Carol A. Scorer、Angela Worby、Graham Riley、Peter Eddershaw、Chris Ioannou、Daniele Donati、Jim J. Hagan、Emiliangelo A. Ratti

  DOI：10.1016/j.bmcl.2006.10.036

  日期：2007.1

  A rational structure-activity relationship study around compound (1) is reported. The lead optimisation programme led to the identification of sulfonamide (25), a molecule combining dopamine D-2/D-3 receptor antagonism with serotonin 5-HT2A, 5-HT2C, 5-HT6 receptor antagonism for an effective treatment of schizophrenia. Compound (25) was shown to possess the required in vivo activity with no EPS liability. (c) 2006 Elsevier Ltd. All rights reserved.
• The discovery and optimisation of benzazepine sulfonamide and sulfones as potent agonists of the motilin receptor
  作者：James M. Bailey、Jackie S. Scott、Jonathan B. Basilla、Victoria J. Bolton、Izzy Boyfield、David G. Evans、Etienne Fleury、Tom D. Heightman、Emma M. Jarvie、Kirk Lawless、Kim L. Matthews、Fiona McKay、Hindy Mok、Alison Muir、Barry S. Orlek、Gareth J. Sanger、Geoffrey Stemp、Alexander J. Stevens、Mervyn Thompson、John Ward、Kalindi Vaidya、Susan M. Westaway

  DOI：10.1016/j.bmcl.2009.09.027

  日期：2009.11

  Optimisation of a series of benzazepine sulfonamide hit compounds identified from high throughput screening led to the discovery of a new series of tractable, potent motilin receptor agonists. (C) 2009 Elsevier Ltd. All rights reserved.