7-amino-8-methyl-1,2,4,5-tetrahydro-3-benzazepine-3-carboxylic acid tert-butyl ester | 583047-19-2

• 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: 7-amino-8-methyl-1,2,4,5-tetrahydro-3-benzazepine-3-carboxylic acid tert-butyl ester
• 英文别名: Tert-butyl 7-amino-8-methyl-1,2,4,5-tetrahydro-3-benzazepine-3-carboxylate
• CAS: 583047-19-2
• 化学式: C₁₆H₂₄N₂O₂
• 分子量: 276.379
• InChiKey: QEVQIUVTBMSADN-UHFFFAOYSA-N

物化性质

• 沸点：
  418.6±45.0 °C(Predicted)
• 密度：
  1.101±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  55.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  7-amino-8-methyl-1,2,4,5-tetrahydro-3-benzazepine-3-carboxylic acid tert-butyl ester 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'-chloro-biphenyl-4-sulfonic acid (8-methyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yl)-amide
  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
• 作为产物：
  描述：

  7-methyl-8-nitro-1,2,4,5-tetrahydrobenzo[d]azepine-3-carboxylic acid tert-butyl ester 在 palladium 10% on activated carbon 氢气 作用下， 以 乙醇 为溶剂， 20.0 ℃ 、344.75 kPa 条件下， 生成 7-amino-8-methyl-1,2,4,5-tetrahydro-3-benzazepine-3-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  [EN] DOPAMINE RECEPTOR MODULATORS AS ANTIPSYCHOTIC AGENTS
  [FR] MODULATEURS DES RECEPTEURS DE DOPAMINE UTILISES COMME AGENTS ANTIPSYCHOTIQUES

  摘要：

  该发明提供了以下化合物的结构（I）： 其中A和B分别代表基团-(CH2)m-和-(CH2)n-；R1代表氢或C1-6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、C1-6氟烷氧基、-(CH2)pC3-6环烷基、-(CH2)pOC3-6环烷基、-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、可选择地取代的芳基、可选择地取代的杂芳基或可选择地取代的杂环烷基；R3代表氢或C1-6烷基；R4代表可选择地取代的芳基或可选择地取代的杂芳基；R5和R6分别独立地代表氢、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)pOC3-6环烷基、-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、可选择地取代的芳基、可选择地取代的杂芳基或可选择地取代的杂环烷基；R7和R8分别独立地代表氢、C1-6烷基或与它们连接的氮或其他原子一起形成氮杂环烷基环或氧代取代的氮杂环烷基环；m和n分别独立地代表1和2中选择的整数；p独立地代表0、1、2和3中选择的整数；并且：Z代表-CR9R10X-或-XCR9R10-，X代表氧、硫、-SO-或-SO2，或Z代表-CONR11-或-NR9CO-，X代表-CH2-、氧、硫、-SO-或-SO2；R9和R10分别独立地代表氢、C1-6烷基或氟代基；R11代表氢或C1-6烷基；或其药学上可接受的盐或溶剂。该发明的化合物在治疗中特别作为抗精神病药物具有用途。

  公开号：

  WO2003095428A1

文献信息

• [EN] CYANOINDOLINE DERIVATIVES AS NIK INHIBITORS<br/>[FR] NOUVEAUX DÉRIVÉS DE CYANOINDOLINE COMME INHIBITEURS DE NIK
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2018002219A1

  公开（公告）日：2018-01-04

  Fused aromatic bicyclic substituted 5-(2-amino-4-pyrimidinyl)- cyanoindoline derivatives (I) useful for therapy and/or prophylaxis in a mammal, and in particular to inhibitors of NF-KB-inducing kinase (NIK - also known as MAP3K14) useful for treating diseases such as cancer, inflammatory disorders, metabolic disorders and autoimmune disorders. The invention is also directed to pharmaceutical compositions comprising such compounds, and to the use of such compounds or pharmaceutical compositions for the prevention or treatment of diseases such as cancer, inflammatory disorders, metabolic disorders including obesity and diabetes, and autoimmune disorders.

  融合的芳香族双环取代5-(2-氨基-4-嘧啶基)-氰基吲哚衍生物（I）用于哺乳动物的治疗和/或预防，特别是用于抑制NF-KB诱导激酶（NIK - 也称为MAP3K14）的抑制剂，用于治疗癌症、炎症性疾病、代谢性疾病和自身免疫性疾病。本发明还涉及包含这些化合物的药物组合物，以及使用这些化合物或药物组合物预防或治疗癌症、炎症性疾病、包括肥胖和糖尿病的代谢性疾病和自身免疫性疾病。
• Benzenesulfonamide derivatives as antipsychotic agents
  申请人：Bromidge Mark Steven

  公开号：US20050222124A1

  公开（公告）日：2005-10-06

  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 1-6 alkyl; R 2 represents hydrogen, halogen, hydroxy, cyano, nitro, hydroxyC 1-6 alkyl, trifluoromethyl, trifluoromethoxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxyC 1-6 alkyl, C 3-7 cycloalkylC 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, C 1-6 alkylsulfonyloxy, C 1-6 alkylsulfonylC 1-6 alkyl, —CO 2 C 1-6 alkyl, —CO 2 NR 7 R 8 , —SO 2 NR 7 R 8 , C 1-6 alkylsulfonamido, C 1-6 alkylsulfonamidoC 1-6 alkyl, —(CH 2 ) p NR 7 R 8 , C 1-6 alkylamidoC 1-6 alkyl, —(CH 2 ) p NR 7 COR 8 , arylsulfonyl, arylsulfonyloxy, arylsulfonylC 1-6 alkyl, arylsulfonamido, arylcarboxamido, arylsulfonamidoC 1-6 alkyl, arylcarboxamidoC 1-6 alkyl, aroyl, aroylC 1-6 alkyl, arylC 1-6 alkanoyl, —SO 2 NR 7 R 8 , optionally substituted aryl, optionally substituted heteroaryl or optionally substituted heterocyclyl, or a group CONR 7 R 8 or SO 2 NR 7 R 8 wherein R 7 and R 8 together may be fused to form a 5- 7-membered aromatic or non-aromatic heterocyclic ring optionally interrupted by an O or S atom; R 3 represents hydrogen or C 1-6 alkyl; Ar represents optionally substituted phenyl or optionally substituted monocyclic heteroaryl group; R 4 represents optionally substituted aryl or optionally substituted heteroaryl; R 7 and R 8 each independently represent hydrogen, C 1-6 alkyl or together form a 5- to 7-membered heterocyclic ring; Z represents a bond, an oxygen atom or C 1-6 alkyl; Y represents 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; q represents an integer from 1 to 3; r represents an integer from 1 to 4; or a pharmaceutically acceptable salt or solvate thereof. The compounds are useful in therapy, in particular as antipsychotic agents.

  本发明提供了化合物的公式（I），其中A和B分别表示基团—（CH2）m-和—（CH2）n-；R1表示氢或C1-6烷基；R2表示氢、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、C1-6烷氧基C1-6烷基、C3-7环烷基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、C1-6烷基磺酰氧基、C1-6烷基磺酰C1-6烷基、—CO2C1-6烷基、—CO2NR7R8、—SO2NR7R8、C1-6烷基磺酰胺基、C1-6烷基磺酰胺基C1-6烷基、—（CH2）pNR7R8、C1-6烷基酰胺基C1-6烷基、—（CH2）pNR7COR8、芳基磺酰基、芳基磺酰氧基、芳基磺酰C1-6烷基、芳基磺酰胺基、芳基羧酰胺基、芳基磺酰胺基C1-6烷基、芳基羧酰胺基C1-6烷基、芳基、芳基C1-6酰基、—SO2NR7R8、可选择取代的芳基、可选择取代的杂芳基或可选择取代的杂环基，或者是一个CONR7R8或SO2NR7R8基团，其中R7和R8可以共轭形成一个5-7成员的芳香族或非芳香族杂环，该杂环可以被O或S原子打断；R3表示氢或C1-6烷基；Ar表示可选择取代的苯基或可选择取代的单环杂芳基；R4表示可选择取代的芳基或可选择取代的杂芳基；R7和R8各自独立地表示氢、C1-6烷基或共同形成一个5-7成员的杂环；Z表示键，氧原子或C1-6烷基；Y表示氢或C1-6烷基；m和n独立地表示选自1和2的整数；p独立地表示选自0、1、2和3的整数；q表示1至3的整数；r表示1至4的整数；或其药学上可接受的盐或溶剂。这些化合物在治疗中有用，特别是作为抗精神病药物。
• Dopamine receptor modulators as antipsychotic agents
  申请人：Cooper Gwyn David

  公开号：US20070043026A1

  公开（公告）日：2007-02-22

  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 1-6 alkyl; R 2 represents hydrogen, halogen, hydroxy, cyano, nitro, hydroxyC 1-6 alkyl, trifluoromethyl, trifluoromethoxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 fluoroalkoxy, —(CH 2 ) p C 3-6 cycloalkyl, —(CH 2 ) p OC 3-6 cycloalkyl, —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 optionally substituted heterocyclyl; R 3 represents hydrogen or C 1-6 alkyl; R 4 represents optionally substituted aryl or optionally substituted heteroaryl; 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 OC 3-6 cycloalkyl, —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 optionally substituted heterocyclyl; R 7 and R 8 each independently represent hydrogen, C 1-6 alkyl or, together with the nitrogen or other atoms to which they are attached, form an azacycloalkyl ring or an oxo-substituted azacycloalkyl ring; m and n independently represent an integer selected from 1 and 2; p independently represents an integer selected from 0, 1, 2 and 3; and either: Z represents —CR 9 R 10 X— or —XCR 9 R 10 — and X represents oxygen, sulfur, —SO— or —SO 2 , or Z represents —CONR 11 — or —NR 9 CO— and X represents —CH 2 —, oxygen, sulfur, —SO— or —SO 2 ; R 9 and R 10 each independently represent hydrogen, C 1-6 alkyl or fluoro; R 11 represents hydrogen or C 1-6 alkyl; or a pharmaceutically acceptable salt or solvate thereof. The compounds of the invention are useful in therapy, in particular as antipsychotic agents.

  本发明提供了式（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C1-6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、C1-6氟烷氧基、—（CH2）pC3-6环烷基、—（CH2）pOC3-6环烷基、—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，可选择取代芳基、可选择取代杂芳基或可选择取代杂环基；R3代表氢或C1-6烷基；R4代表可选择取代的芳基或可选择取代的杂芳基；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）pOC3-6环烷基、—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，可选择取代芳基、可选择取代杂芳基或可选择取代杂环基；R7和R8各自独立地代表氢、C1-6烷基或与它们附着的氮或其他原子一起形成一个氮杂环烷基或氧代取代的氮杂环烷基环；m和n各自独立地表示从1和2中选择的整数；p独立地表示从0、1、2和3中选择的整数；且：要么：Z表示—CR9R10X—或—XCR9R10—，X表示氧、硫、—SO—或—SO2，或者Z表示—CONR11—或—NR9CO—，X表示—CH2—、氧、硫、—SO—或—SO2；R9和R10各自独立地代表氢、C1-6烷基或氟；R11代表氢或C1-6烷基；或其药学上可接受的盐或溶剂。本发明的化合物在治疗中有用，特别是作为抗精神病药物。
• Cyanoindoline derivatives as NIK inhibitors
  申请人：Janssen Pharmaceutica NV

  公开号：US11186589B2

  公开（公告）日：2021-11-30

  The present invention relates to pharmaceutical agents useful for therapy and/or prophylaxis in a mammal, and in particular to inhibitors of NF-κB-inducing kinase (NIK—also known as MAP3K14) useful for treating diseases such as cancer, inflammatory disorders, metabolic disorders and autoimmune disorders. The invention is also directed to pharmaceutical compositions comprising such compounds, and to the use of such compounds or pharmaceutical compositions for the prevention or treatment of diseases such as cancer, inflammatory disorders, metabolic disorders including obesity and diabetes, and autoimmune disorders.

  本发明涉及可用于哺乳动物治疗和/或预防的药物制剂，尤其涉及可用于治疗癌症、炎症性疾病、代谢性疾病和自身免疫性疾病等疾病的NF-κB诱导激酶（NIK-又称MAP3K14）抑制剂。本发明还涉及包含此类化合物的药物组合物，以及使用此类化合物或药物组合物预防或治疗癌症、炎症性疾病、代谢紊乱（包括肥胖和糖尿病）和自身免疫性疾病等疾病。
• BENZENESULFONAMIDE DERIVATIVES AS ANTIPSYCHOTIC AGENTS
  申请人：GLAXO GROUP LIMITED

  公开号：EP1474399A1

  公开（公告）日：2004-11-10