benzyl (5-(4-methoxyphenyl)-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)carbamate | 376584-91-7

• 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: benzyl (5-(4-methoxyphenyl)-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)carbamate
• 英文别名: benzyl N-[5-(4-methoxyphenyl)-2-oxo-1,3-dihydro-1,4-benzodiazepin-3-yl]carbamate
• CAS: 376584-91-7
• 化学式: C₂₄H₂₁N₃O₄
• 分子量: 415.448
• InChiKey: MXOIRHVRRHQDCB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  89
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  benzyl (5-(4-methoxyphenyl)-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)carbamate 在 劳森试剂 、 一水合肼 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 20.0h， 生成 benzyl (2-hydrazineylidene-5-(4-methoxyphenyl)-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)carbamate
  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：

  氨基甲酸苄酯 在 N-甲基吗啉 、 草酰氯 、 氨 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 38.0h， 生成 benzyl (5-(4-methoxyphenyl)-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)carbamate
  参考文献：
  名称：

  1,4-Benzodiazepines as Inhibitors of Respiratory Syncytial Virus

  摘要：

  Respiratory syncytial virus (RSV) is the cause of one-fifth of all lower respiratory tract infections worldwide and is increasingly being recognized as a serious threat to patient groups with poorly functioning immune systems. Our approach to finding a novel inhibitor of this virus was to screen a 20 000-member diverse library in a whole cell XTT assay. Parallel assays were carried out in the absence of virus in order to quantify any associated cell toxicity. This identified 100 compounds with IC50's less than 50 mu M. A-33903 (18), a 1,4-benzodiazepine analogue, was chosen as the starting point for lead optimization. This molecule was moderately active and demonstrated good pharmacokinetic properties. The most potent compounds identified from this work were A-58568 (47), A-58569 (44), and A-62066 (46), where modifications to the aromatic substitution enhanced potency, and A-58175 (42), where the amide linker was modified.

  DOI：

  10.1021/jm051185t

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。
• N-SUBSTITUTED BIS(FLUOROALKYL)-1,4-BENZODIAZEPINONE COMPOUNDS
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US20150246892A1

  公开（公告）日：2015-09-03

  Disclosed are compounds of Formula (I): wherein: R 1 is —CH 2 CH 2 CF 3 ; R 2 is —CH 2 CH 2 CF 3 , or —CH 2 CH 2 CH 2 CF 3 ; R 3 is —CH 2 CF 3 , —CH 2 CN, —CH 2 (cyclopropyl), pyridinyl, chloropyridinyl, or tetrahydropyranyl; Ring A is phenyl or pyridinyl; R a , R b , y, and z are defined herein. Also disclosed are methods of using such compounds to inhibit the Notch receptor, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as cancer.

  本发明涉及化合物的公式（I）：其中：R1为— CF3；R2为— CF3或— CF3；R3为— CF3、— CN、—CH2（环丙基）、吡啶基、氯吡啶基或四氢吡喃基；环A为苯基或吡啶基；Ra、Rb、y和z在此定义。还公开了使用这些化合物抑制Notch受体的方法和包含这些化合物的制药组合物。这些化合物可用于治疗、预防或减缓多种治疗领域的疾病或障碍，如癌症。
• N-substituted bis(fluoroalkyl)-1,4-benzodiazepinone compounds
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US09242940B2

  公开（公告）日：2016-01-26

  Disclosed are compounds of Formula (I): wherein: R1 is —CH2CH2CF3; R2 is —CH2CH2CF3, or —CH2CH2CH2CF3; R3 is —CH2CF3, —CH2CN, —CH2(cyclopropyl), pyridinyl, chloropyridinyl, or tetrahydropyranyl; Ring A is phenyl or pyridinyl; Ra, Rb, y, and z are defined herein. Also disclosed are methods of using such compounds to inhibit the Notch receptor, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as cancer.

  本发明涉及式(I)的化合物：其中：R1为— CF3；R2为— CF3或— CF3；R3为— CF3、— CN、—CH2（环丙基）、吡啶基、氯吡啶基或四氢吡喃基；环A为苯基或吡啶基；Ra、Rb、y和z在此有定义。本发明还涉及使用这种化合物来抑制Notch受体的方法，以及包含这种化合物的制药组合物。这些化合物在治疗、预防或减缓多种治疗领域的疾病或障碍方面非常有用，如癌症。
• [EN] N-SUBSTITUTED BIS(FLUOROALKYL)-1,4-BENZODIAZEPINONE COMPOUNDS<br/>[FR] COMPOSÉS BIS(FLUOROALKYL)-1,4-BENZODIAZÉPINONE N-SUBSTITUÉS UTILISÉS COMME INHIBITEURS DE NOTCH
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2014047393A9

  公开（公告）日：2014-05-01