tert-butyl 7-amino-8-methoxy-1,2,4,5-tetrahydro-3H-benzo[d]azepine-3-carboxylate | 583025-98-3

• 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: tert-butyl 7-amino-8-methoxy-1,2,4,5-tetrahydro-3H-benzo[d]azepine-3-carboxylate
• 英文别名: 7-amino-8-methoxy-1,2, 4, 5-tetrahydro-3-benzazepine-3-carboxylic acid tert-butyl ester；tert-Butyl 7-amino-8-methoxy-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate；tert-butyl 8-amino-7-methoxy-1,2,4,5-tetrahydro-3-benzazepine-3-carboxylate
• CAS: 583025-98-3
• 化学式: C₁₆H₂₄N₂O₃
• 分子量: 292.378
• InChiKey: JVJWENUWJAZYKF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  64.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 7-amino-8-methoxy-1,2,4,5-tetrahydro-3H-benzo[d]azepine-3-carboxylate 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-(4-chlorophenyl)-N-(7-methoxy-2,3,4,5-tetrahydro-1H-3-benzazepin-8-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
• 作为产物：
  描述：

  3-BOC-7-氨基-1,2,4,5-四氢苯并[D]氮杂卓 在 N-碘代丁二酰亚胺 、 copper(l) iodide 、 1,10-菲罗啉 、 caesium carbonate 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 18.5h， 生成 tert-butyl 7-amino-8-methoxy-1,2,4,5-tetrahydro-3H-benzo[d]azepine-3-carboxylate
  参考文献：
  名称：

  [EN] CYANOINDOLINE DERIVATIVES AS NIK INHIBITORS
  [FR] NOUVEAUX DÉRIVÉS DE CYANOINDOLINE COMME INHIBITEURS DE NIK

  摘要：

  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。

  公开号：

  WO2018002219A1

文献信息

• [EN] PYRROLOTRIAZINES AS ALK AND JAK2 INHIBITORS<br/>[FR] PYRROLOTRIAZINES EN TANT QU'INHIBITEURS D'ALK ET DE JAK2
  申请人：CEPHALON INC

  公开号：WO2010071885A1

  公开（公告）日：2010-06-24

  The present invention provides a compound of formula (I) or a salt form thereof, wherein Q1, Q2, Q3, and Q4 are as defined herein. The compound of formula (I) has ALK and/or JAK2 inhibitory activity, and may be used to treat proliferative disorders.

  本发明提供了一种式（I）的化合物或其盐形式，其中Q1、Q2、Q3和Q4如本文所定义。式（I）的化合物具有ALK和/或JAK2抑制活性，并可用于治疗增殖性疾病。
• PYRIMIDINE-2,4-DIAMINE DERIVATIVE AND ANTICANCER PHARMACEUTICAL COMPOSITION COMPRISING SAME AS EFFECTIVE INGREDIENT
  申请人：KOREA RESEARCH INSTITUTE OF CHEMICAL TECHNOLOGY

  公开号：US20170145007A1

  公开（公告）日：2017-05-25

  The present invention relates to a pyrimidine-2,4-diamine derivative or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition for prevention or treatment of cancer comprising the same as an effective ingredient. A compound according to the present invention has the good effect of inhibiting anaplastic lymphoma kinase (ALK) activity, whereby a therapeutic effect on cancer cells having an anaplastic lymphoma kinase (ALK) fusion protein such as EML4-ALK, NPM-ALK, etc. can be enhanced and it is expected that a recurrence of cancer will be effectively inhibited. As such, the compound can be effectively used in a pharmaceutical composition for prevention or treatment of cancer.

  本发明涉及一种嘧啶-2,4-二胺衍生物或其药学上可接受的盐，以及包含该衍生物作为有效成分的用于预防或治疗癌症的药物组合物。根据本发明的化合物具有良好的抑制间变性淋巴瘤激酶（ALK）活性的效果，从而能够增强对含有间变性淋巴瘤激酶（ALK）融合蛋白（如EML4-ALK、NPM-ALK等）的癌细胞的治疗效果，并有望有效抑制癌症的复发。因此，该化合物可有效地用于预防或治疗癌症的药物组合物中。
• [EN] DOPAMINE RECEPTOR MODULATORS AS ANTIPSYCHOTIC AGENTS<br/>[FR] MODULATEURS DES RECEPTEURS DE DOPAMINE UTILISES COMME AGENTS ANTIPSYCHOTIQUES
  申请人：GLAXO GROUP LTD

  公开号：WO2003095428A1

  公开（公告）日：2003-11-20

  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, C1-6fluoroalkoxy, -(CH2)pC3-6cycloalkyl, -(CH2)pOC3-6cycloalkyl, -COC1-6alkyl, -SO2C1-6alkyl, -SOC1-6alkyl, -S-C1-6alkyl, -CO2C1-6alkyl, -CO2NR7R8, -SO2NR7R8, -(CH2)pNR7R8, -(CH2)pNR7COR8, optionally substituted aryl, optionally substituted heteroaryl or optionally substituted heterocyclyl; R3 represents hydrogen or C1-6alkyl; R4 represents optionally substituted aryl or optionally substituted heteroaryl; R5 and R6 each independently represent hydrogen, halogen, hydroxy, cyano, nitro, hydroxyC1-6alkyl, trifluoromethyl, trifluoromethoxy, C1-6alkyl, C1-6alkoxy, -(CH2)pC3-6cycloalkyl, -(CH2)pOC3-6cycloalkyl, -COC1-6alkyl, -SO2C1-6alkyl, -SOC1-6alkyl, -S-C1-6alkyl, -CO2C1-6alkyl, -CO2NR7R8, -SO2NR7R8, -(CH2)pNR7R8, -(CH2)pNR7COR8, optionally substituted aryl, optionally substituted heteroaryl or optionally substituted heterocyclyl; R7 and R8 each independently represent hydrogen, C1-6alkyl 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 -CR9R10X- or -XCR9R10- and X represents oxygen, sulfur, -SO- or -SO2, or Z represents -CONR11- or -NR9CO- and X represents -CH2-, oxygen, sulfur, -SO- or -SO2; R9 and R10 each independently represent hydrogen, C1-6alkyl or fluoro; R11 represents hydrogen or C1-6alkyl;or a pharmaceutically acceptable salt or solvate thereof.The compounds of the invention are useful in therapy, in particular as antipsychotic agents.

  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。
• [EN] SULFONAMIDE DERIVATIVES AS ANTIPSYCHOTIC AGENTS<br/>[FR] DERIVES DE SULFONAMIDE UTILISES COMME AGENTS ANTIPSYCHOTIQUES
  申请人：GLAXO GROUP LTD

  公开号：WO2004031181A1

  公开（公告）日：2004-04-15

  The invention provides compounds of formula (I) wherein A and B represent the groups -(CH2)m- and -(CH2)n- respectively; R1 represents C1-6alkyl; R2 represents hydrogen, halogen, hydroxy, cyano, nitro, hydroxyC1-6alkyl, trifluoromethyl, trifluoromethoxy, C1-6alkyl, C1-6alkoxy, -(CH2)pC3-6cycloalkyl, -(CH2)pOC3-6cycloalkyl, -COC1-6alkyl, -SO2C1-6alkyl, -SOC1-6alkyl, -S-C1-6alkyl, -CO2C1-6alkyl, -CO2NR4R5, -SO2NR4R5, -(CH2)pNR4R5, -(CH2)pNR4COR5, an optionally substituted aryl group, an optionally substituted heteroaryl group or an optionally substituted heterocyclyl group; R3 represents hydrogen or C1-6alkyl; Ar1 represents an optionally substituted heteroaryl group; Ar2 represents an optionally substituted phenyl or an optionally substituted heteroaryl group; Y represents a bond, -O-, -C1-6alkyl-, -CR6R7X-, -XCR6R7-, -NR8CO- or -CONR8-; X represents oxygen, sulfur, -SO- or -SO2-; R4 and R5 each independently represent hydrogen or C1-6alkyl or, together with the nitrogen or other atoms to which they are attached, form an azacycloalkyl ring or an oxo-substituted azacycloalkyl ring; R6 and R7 each independently represent hydrogen, C1-6alkyl or fluoro; R8 represents 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, solvate or pharmaceutically acceptable derivative thereof. The compounds are useful in therapy, in particular as antipsychotic agents.

  该发明提供了以下结构的化合物（I），其中A和B分别代表基团-(CH2)m-和-(CH2)n-；R1代表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、-(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、-CO2NR4R5、-SO2NR4R5、-(CH2)pNR4R5、-(CH2)pNR4COR5、一个可选择取代的芳基、一个可选择取代的杂芳基或一个可选择取代的杂环烷基；R3代表氢或C1-6烷基；Ar1代表一个可选择取代的杂芳基；Ar2代表一个可选择取代的苯基或一个可选择取代的杂芳基；Y代表一个键、-O-、-C1-6烷基-、-CR6R7X-、-XCR6R7-、-NR8CO-或-CONR8-；X代表氧、硫、-SO-或-SO2-；R4和R5分别独立地代表氢或C1-6烷基，或者与它们连接的氮或其他原子一起形成一个氮杂环烷基环或一个氧代取代的氮杂环烷基环；R6和R7分别独立地代表氢、C1-6烷基或氟；R8代表氢或C1-6烷基；m和n独立地代表从1和2中选择的整数；p独立地代表从0、1、2和3中选择的整数；或其药学上可接受的盐、溶剂或药学上可接受的衍生物。这些化合物在治疗中很有用，特别是作为抗精神病药物。
• 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。