[benzotriazol-1-yl(2-(4-chloro-benzoyl)-phenylcarbamoyl)-methyl]-carbamic acid benzyl ester | 1206716-08-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: [benzotriazol-1-yl(2-(4-chloro-benzoyl)-phenylcarbamoyl)-methyl]-carbamic acid benzyl ester
• 英文别名: benzyl N-[1-(benzotriazol-1-yl)-2-[2-(4-chlorobenzoyl)anilino]-2-oxoethyl]carbamate
• CAS: 1206716-08-6
• 化学式: C₂₉H₂₂ClN₅O₄
• 分子量: 539.978
• InChiKey: KKZZQKMVKQAZTM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  39
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  [benzotriazol-1-yl(2-(4-chloro-benzoyl)-phenylcarbamoyl)-methyl]-carbamic acid benzyl ester 在 ammonium acetate 、 氨 、 氢溴酸 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 反应 25.5h， 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
• 作为产物：
  描述：

  2-氨基-4'-氯二苯甲酮 、 2-(1H-苯并[d][1,2,3]噻唑-1-基)-2-(((苄氧基)羰基)氨基)乙酸 在 草酰氯 、 N,N-二甲基甲酰胺 、 N-甲基吗啉 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 [benzotriazol-1-yl(2-(4-chloro-benzoyl)-phenylcarbamoyl)-methyl]-carbamic acid benzyl ester
  参考文献：
  名称：

  WO2007/34127

  摘要：

  公开号：

文献信息

• 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)-。
• WO2007/34127
  申请人：——

  公开号：——

  公开（公告）日：——
• 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)-.
• Discovery of Epigenetic Regulator I-BET762: Lead Optimization to Afford a Clinical Candidate Inhibitor of the BET Bromodomains
  作者：Olivier Mirguet、Romain Gosmini、Jérôme Toum、Catherine A. Clément、Mélanie Barnathan、Jean-Marie Brusq、Jacqueline E. Mordaunt、Richard M. Grimes、Miriam Crowe、Olivier Pineau、Myriam Ajakane、Alain Daugan、Phillip Jeffrey、Leanne Cutler、Andrea C. Haynes、Nicholas N. Smithers、Chun-wa Chung、Paul Bamborough、Iain J. Uings、Antonia Lewis、Jason Witherington、Nigel Parr、Rab K. Prinjha、Edwige Nicodème

  DOI：10.1021/jm401088k

  日期：2013.10.10

  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.