3-amino-5-(4-chlorophenyl)-1H-benzo[e][1,4]diazepin-2(3H)-one | 885956-47-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: 3-amino-5-(4-chlorophenyl)-1H-benzo[e][1,4]diazepin-2(3H)-one
• 英文别名: 3-amino-5-(4-chlorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one；3-Amino-5-(4-chlorophenyl)-1,3-dihydro-1,4-benzodiazepin-2-one
• CAS: 885956-47-8
• 化学式: C₁₅H₁₂ClN₃O
• 分子量: 285.733
• InChiKey: WERAPAVZMBDVPV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.41
• 重原子数：
  20.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  67.48
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  3-amino-5-(4-chlorophenyl)-1H-benzo[e][1,4]diazepin-2(3H)-one 在 劳森试剂 、 一水合肼 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 甲苯 为溶剂， 反应 22.0h， 生成
  参考文献：
  名称：

  Discovery of Epigenetic Regulator I-BET762: Lead Optimization to Afford a Clinical Candidate Inhibitor of the BET Bromodomains

  摘要：

  The bromo and extra C-terminal domain (BET) family of bromodomains are involved in binding epigenetic marks on histone proteins, more specifically acetylated lysine residues. This paper describes the discovery and structure activity relationships (SAR) of potent benzodiazepine inhibitors that disrupt the function of the BET family of bromodomains (BRD2, BRD3, and BRD4). This work has yielded a potent, selective compound I-BET762 that is now under evaluation in a phase I/II clinical trial for nuclear protein in testis (NUT) midline carcinoma and other cancers.

  DOI：

  10.1021/jm401088k
• 作为产物：
  描述：

  在 ammonium acetate 、 氢溴酸 、 溶剂黄146 作用下， 反应 24.5h， 生成 3-amino-5-(4-chlorophenyl)-1H-benzo[e][1,4]diazepin-2(3H)-one
  参考文献：
  名称：

  Discovery of Epigenetic Regulator I-BET762: Lead Optimization to Afford a Clinical Candidate Inhibitor of the BET Bromodomains

  摘要：

  The bromo and extra C-terminal domain (BET) family of bromodomains are involved in binding epigenetic marks on histone proteins, more specifically acetylated lysine residues. This paper describes the discovery and structure activity relationships (SAR) of potent benzodiazepine inhibitors that disrupt the function of the BET family of bromodomains (BRD2, BRD3, and BRD4). This work has yielded a potent, selective compound I-BET762 that is now under evaluation in a phase I/II clinical trial for nuclear protein in testis (NUT) midline carcinoma and other cancers.

  DOI：

  10.1021/jm401088k

文献信息

• Condensed Azepine Derivatives As Bromodomain Inhibitors
  申请人：Crowe Miriam

  公开号：US20120202799A1

  公开（公告）日：2012-08-09

  Benzodiazepine compounds of formula (I) and salts thereof, pharmaceutical compositions containing such compounds and their use in therapy.

  苯二氮卓类化合物的化学式（I）及其盐，含有这类化合物的药物组合物以及它们在治疗中的应用。
• [EN] CONDENSED AZEPINE DERIVATIVES AS BROMODOMAIN INHIBITORS<br/>[FR] DÉRIVÉS CONDENSÉS D'AZÉPINES CONVENANT COMME INHIBITEURS DU BROMODOMAINE
  申请人：GLAXOSMITHKLINE LLC

  公开号：WO2011054844A1

  公开（公告）日：2011-05-12

  Benzodiazepine compounds of formula (I) and salts thereof, pharmaceutical compositions containing such compounds and their use in therapy.

  苯二氮卓类化合物的化学式（I）及其盐，含有这类化合物的药物组合物以及它们在治疗中的应用。
• BENZODIAZEPINE DERIVATIVES FOR TREATING HEPATITIS C INFECTION
  申请人：Dennison Helena

  公开号：US20090318427A1

  公开（公告）日：2009-12-24

  Use of a benzodiazepine of formula (I), or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for use in treating or preventing a hepatitis C infection, wherein: —R 1 represents C 1-6 alkyl, aryl or heteroaryl; —R 2 represents hydrogen or C 1-6 alkyl; —each R 3 is the same or different and represents halogen, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 haloalkyl, C 1-6 haloalkoxy, amino, mono(C 1-6 alkyl)amino, di(C 1-6 alkyl)amino, nitro, cyano, —CO 2 R′, —CONR′R″, —NH—C 0 -R′, —S(O)R′, —S(O) 2 R′, —NH—S(O) 2 R′, —S(O)NR′R″ or —S(O) 2 NR′R″, wherein each R′ and R″ is the same or different and represents hydrogen or C 1-6 alkyl; —n is from 0 to 3; —R 4 represents hydrogen or C 1-6 alkyl; —R 5 represents C 1-6 alkyl, aryl, heteroaryl, carbocyclyl, heterocyclyl, aryl-(C 1-6 alkyl)-, heteroaryl-(C 1-6 alkyl)-, carbocyclyl-(C 1-6 alkyl)-, heterocyclyl-(C 1-6 alkyl)-, aryl-(C 1-6 hydroxyalkyl)-, heteroaryl-(C 1-6 hydroxyalkyl)-, carbocyclyl-(C 1-6 hydroxyalkyl)-, heterocyclyl-(C 1-6 hydroxyalkyl)-, aryl-C(O)—C(O)—, heteroaryl-C(O)—C(O)—, carbocyclyl-C(O)—C(O)—, heterocyclyl-C(O)—C(O)— or —XR 6 ; —X represents —CO—, —S(O)— or —S(O) 2 —; and —R 6 represents C 1-6 alkyl, hydroxy, C 1-6 alkoxy, C 1-6 alkylthio, aryl, heteroaryl, carbocyclyl, heterocyclyl, aryl-(C 1-6 alkyl)-, heteroaryl-(C 1-6 alkyl)-, carbocyclyl-(C 1-6 alkyl)-, heterocyclyl-(C 1-6 alkyl)-, aryl-(C 1-6 alkyl)-O—, heteroaryl-(C 1-6 alkyl)-O—, carbocyclyl-(C 1-6 alkyl)-O—, heterocyclyl-(C 1-6 alkyl)-O— or —NR′R″ wherein each R′ and R″ is the same or different and represents hydrogen, C 1-6 alkyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, aryl-(C 1-6 alkyl)-, heteroaryl-(C 1-6 alkyl)-, carbocyclyl-(C 1-6 alkyl)- or heterocyclyl-(C 1-6 alkyl)-.

  使用式(I)苯二氮平或其药学上可接受的盐制备药物，用于治疗或预防丙型肝炎感染，其中： - R1代表C1-6烷基，芳基或杂环芳基； - R2代表氢或C1-6烷基； - 每个R3相同或不同，代表卤素，羟基，C1-6烷基，C1-6烷氧基，C1-6烷基硫基，C1-6卤代烷基，C1-6卤代烷氧基，氨基，单(C1-6烷基)氨基，双(C1-6烷基)氨基，硝基，氰基，-CO2R'，-CONR'R"，-NH-C0-R'，-S(O)R'，-S(O)2R'，-NH-S(O)2R'，-S(O)NR'R"或-S(O)2NR'R"，其中每个R'和R"相同或不同，代表氢或C1-6烷基； - n为0至3； - R4代表氢或C1-6烷基； - R5代表C1-6烷基，芳基，杂环芳基，碳环基，杂环基，芳基-(C1-6烷基)-，杂环芳基-(C1-6烷基)-，碳环基-(C1-6烷基)-，杂环基-(C1-6烷基)-，芳基-(C1-6羟基烷基)-，杂环芳基-(C1-6羟基烷基)-，碳环基-(C1-6羟基烷基)-，杂环基-(C1-6羟基烷基)-，芳基-C(O)-C(O)-，杂环芳基-C(O)-C(O)-，碳环基-C(O)-C(O)-，杂环基-C(O)-C(O)-或-XR6； - X代表-CO-，-S(O)-或-S(O)2-； - R6代表C1-6烷基，羟基，C1-6烷氧基，C1-6烷基硫基，芳基，杂环芳基，碳环基，杂环基，芳基-(C1-6烷基)-，杂环芳基-(C1-6烷基)-，碳环基-(C1-6烷基)-，杂环基-(C1-6烷基)-，芳基-(C1-6烷基)-O-，杂环芳基-(C1-6烷基)-O-，碳环基-(C1-6烷基)-O-，杂环基-(C1-6烷基)-O-或-NR'R"，其中每个R'和R"相同或不同，代表氢，C1-6烷基，碳环基，杂环基，芳基，杂环芳基，芳基-(C1-6烷基)-，杂环芳基-(C1-6烷基)-，碳环基-(C1-6烷基)-或杂环基-(C1-6烷基)-。
• US8039616B2
  申请人：——

  公开号：US8039616B2

  公开（公告）日：2011-10-18
• [EN] BENZODIAZEPINE DERIVATIVES FOR TREATING HEPATITIS C INFECTION<br/>[FR] DÉRIVÉS DE BENZODIAZÉPINE POUR LE TRAITEMENT D'UNE INFECTION PAR L'HÉPATITE C
  申请人：ARROW THERAPEUTICS LTD

  公开号：WO2007034127A1

  公开（公告）日：2007-03-29

  [EN] Use of a benzodiazepine of formula (I), or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for use in treating or preventing a hepatitis C infection, wherein: - R¹ represents C_1-6 alkyl, aryl or heteroaryl; - R² represents hydrogen or C_1-6 alkyl; - each R³ is the same or different and represents halogen, hydroxy, C_1-6 alkyl, C_1-6 alkoxy, C_1-6 alkylthio, C_1-6 haloalkyl, C_1-6 haloalkoxy, amino, mono(C_1-6 alkyl)amino, di(C_1-6 alkyl)amino, nitro, cyano, -CO₂R', -CONR'R", -NH-C0-R', -S(O)R', -S(O)₂R', -NH-S(O)₂R', -S(O)NR'R" or -S(O)₂NR'R", wherein each R' and R" is the same or different and represents hydrogen or C_1-6 alkyl; - n is from 0 to 3; - R⁴ represents hydrogen or C_1-6 alkyl; - R⁵ represents C_1-6alkyl, aryl, heteroaryl, carbocyclyl, heterocyclyl, aryl-(C_1-6 alkyl)-, heteroaryl-(C_1-6 alkyl)-, carbocyclyl-(C_1-6 alkyl)-, heterocyclyl-(C_1-6 alkyl)-, aryl-(C_1-6 hydroxyalkyl)-, heteroaryl-(C_1-6hydroxyalkyl)-, carbocyclyl-(C_1-6 hydroxyalkyl)-, heterocyclyl-(C_1-6hydroxyalkyl)-, aryl-C(O)-C(O)-, heteroaryl-C(O)-C(O)-, carbocyclyl-C(O)-C(O)-, heterocyclyl-C(O)-C(O)- or -XR⁶; - X represents -CO-, -S(O)- or -S(O)₂-; and - R⁶ represents C_1-6 alkyl, hydroxy, C_1-6 alkoxy, C_1-6 alkylthio, aryl, heteroaryl, carbocyclyl, heterocyclyl, aryl-(C_1-6 alkyl)-, heteroaryl-(C_1-6 alkyl)-, carbocyclyl-(C_1-6 alkyl)-, heterocyclyl-(C_1-6 alkyl)-, aryl-(C_1-6 alkyl)-O-, heteroaryl-(C_1-6 alkyl)-O-, carbocyclyl-(C_1-6 alkyl)-O-, heterocyclyl-(C_1-6 alkyl)-O- or -NR'R" wherein each R' and R" is the same or different and represents hydrogen, C_1-6 alkyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, aryl-(C_1-6 alkyl)-, heteroaryl-(C_1-6 alkyl)-, carbocyclyl-(C_1-6 alkyl)- or heterocyclyl-(C_1-6 alkyl)-.
  [FR] La présente invention concerne l'utilisation d'une benzodiazépine de formule (I) ou d'un sel pharmaceutiquement acceptable de celle-ci, pour la fabrication d'un médicament destiné à traiter ou à prévenir une infection par l'hépatite C. Dans la formule précitée, - R¹ représente alkyle en C_1-6, aryle ou hétéroaryle; - R² représente hydrogène ou alkyle en C_1-6; - chaque R³ est identique ou différent et représente halogène, hydroxy, alkyle en C_1-6, alkoxy en C_1-6, alkylthio en C_1-6, haloalkyle en C_1-6, haloalkoxy en C_1-6, amino, mono(C_1-6 alkyl)amino, di(C_1-6 alkyl)amino, nitro, cyano, -CO₂R', -CONR'R', -NH-C0-R', -S(O)R', -S(O)₂R', -NH-S(O)₂R', -S(O)NR'R' ou -S(O)₂NR'R', chaque R' et R' étant les mêmes ou différents et représentant hydrogène ou alkyle en C_1-6; - n est compris entre 0 et 3; - R⁴ représente hydrogène ou alkyle en C_1-6; - R⁵ représente alkyle en C_1-6, aryle, hétéroaryle, carbocyclyle, hétérocyclyle, aryl-(C_1-6 alkyl)-, hétéroaryl-(C_1-6 alkyl)-, carbocyclyl-(C_1-6 alkyl)-, hétérocyclyl-(C_1-6 alkyl)-, aryl-(C_1-6 hydroxyalkyl)-, hétéroaryl-(C_1-6hydroxyalkyl)-, carbocyclyl-(C_1-6 hydroxyalkyl)-, hétérocyclyl-(C_1-6hydroxyalkyl)-, aryl-C(O)-C(O)-, hétéroaryl-C(O)-C(O)-, carbocyclyl-C(O)-C(O)-, hétérocyclyl-C(O)-C(O)- ou -XR⁶; - X représente -CO-, -S(O)- ou -S(O)₂-; et - R⁶ représente alkyle en C_1-6, hydroxy, alkoxy C_1-6, alkylthio en C_1-6, aryle, hétéroaryle, carbocyclyle, hétérocyclyle, aryl-(C_1-6 alkyl)-, hétéroaryl-(C_1-6 alkyl)-, carbocyclyl-(C_1-6 alkyl)-, hétérocyclyl-(C_1-6 alkyl)-, aryl-(C_1-6 alkyl)-O-, hétéroaryl-(C_1-6 alkyl)-O-, carbocyclyl-(C_1-6 alkyl)-O-, hétérocyclyl-(C_1-6 alkyl)-O- ou -NR'R', R' et R' étant les mêmes ou différents et représentant hydrogène, alkyle en C_1-6,carbocyclyle, hétérocyclyle, aryle, hétéroaryle, aryl-(C_1-6 alkyl)-, hétéroaryl-(C_1-6 alkyl)-, carbocyclyl-(C_1-6 alkyl)- ou hétérocyclyl-(C_1-6 alkyl)-.