phenylmethyl (1-methyl-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl)carbamate | 146135-18-4

• 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: phenylmethyl (1-methyl-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl)carbamate
• 英文别名: GW841819X；phenylmethyl [6-phenyl-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]carbamate；1-methyl-6-phenyl-4-benzyloxycarbonylamino-4H-[1,2,4]triazolo-[4,3-a][1,4]benzodiazepine；Carbamic acid, (1-methyl-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl)-, phenylmethyl ester (9CI)；benzyl N-(1-methyl-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl)carbamate
• CAS: 146135-18-4
• 化学式: C₂₅H₂₁N₅O₂
• 分子量: 423.474
• InChiKey: TUWDLUFFAHHNEF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  81.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  phenylmethyl (1-methyl-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl)carbamate 在 palladium 10% on activated carbon 吡啶 、 1,4-环己二烯 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 ethyl (1-methyl-6-phenyl-4H-benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepin-4-yl)carbamate
  参考文献：
  名称：

  Condensed Azepine Derivatives As Bromodomain Inhibitors

  摘要：

  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。

  公开号：

  US20120202799A1
• 作为产物：
  描述：

  phenylmethyl N-[2,3-dihydro-5-phenyl-2-thioxo-1H-1,4-benzodiazepin-3-yl]carbamate 在 硫酸 、 肼 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 11.5h， 生成 phenylmethyl (1-methyl-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl)carbamate
  参考文献：
  名称：

  Cholecystokinin antagonists. Synthesis and biological evaluation of 4-substituted 4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepines

  摘要：

  A series of 4-substituted 4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepines was prepared by standard methodology. These compounds were tested in vitro as antagonists of the binding of [125I]cholecystokinin (CCK) to rat pancreas and guinea pig brain receptors and of the binding of [125I]gastrin to guinea pig gastric glands. All compounds proved to have greater affinity for the peripheral CCK receptor with some analogues having IC50's in the subnanomolar range. In vivo activity of selected compounds in mice is presented and the structure/activity profile of this class of benzodiazepines as CCK antagonists is discussed.

  DOI：

  10.1021/jm00396a028

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。
• Triazolobenzodiazepines
  申请人：Merck & Co., Inc.

  公开号：US05185331A1

  公开（公告）日：1993-02-09

  Pharmaceutical compositions containing Triazolobenzodiazepines of the formula: ##STR1## are disclosed which are useful in the treatment of panic disorder or anxiety disorder.

  揭示了含有Triazolobenzodiazepines的制药组合物，其化学式为：##STR1##，可用于治疗惊恐症或焦虑症。
• [EN] P53 MODULATORS AND USES THEREOF<br/>[FR] MODULATEURS DE p53 ET UTILISATIONS DE CEUX-CI
  申请人：UNIV CALIFORNIA

  公开号：WO2021087096A1

  公开（公告）日：2021-05-06

  Described herein, inter alia, are p53 modulator compounds and methods of using the same. In an aspect is provided a p53 protein covalently bonded to a compound described herein. In an aspect is provided a pharmaceutical composition including a compound described herein and a pharmaceutically acceptable excipient. In an aspect is provided a method of treating cancer in a subject in need of such treatment, including administering to the subject an effective amount of a compound described herein.

  本文描述了p53调节剂化合物及其使用方法等内容。在一个方面，提供了一种p53蛋白与本文描述的化合物共价结合的方法。在一个方面，提供了一种包含本文描述的化合物和药用辅料的药物组合物。在一个方面，提供了一种治疗需要此类治疗的受试者的癌症的方法，包括向受试者施用本文描述的化合物的有效量。
• Novel Process
  申请人：Bamborough Paul

  公开号：US20120252139A1

  公开（公告）日：2012-10-04

  A process for the identification of compounds with a molecular weight in the range 100 to 750 which inhibit the binding of the first and/or second bromodomains of human BRD-2 to 4 to acetylated lysine residues of their physiological partner proteins which comprises selecting those compounds which are able to: a) form a hydrogen bonding interaction in which the compound accepts a hydrogen bond from the sidechain NH2 group of the asparagine residue found at: BRD-2 BRD-2 BRD-3 BRD-4 BRD-4 BD1 BD2 BD1 BRD-3 BD2 BD1 BD2 ASN156 ASN429 ASN116 ASN391 ASN140 ASN433 or b) accept a water-mediated hydrogen bond in which the compound accepts a hydrogen bond from a water that is itself hydrogen-bonded to the sidechain hydroxyl of the tyrosine residue found at BRD-2 BRD-3 BRD-4 BD1 BRD-2 BD2 BD1 BRD-3 BD2 BD1 BRD-4 BD2 TYR113 TYR386 TYR73 TYR348 TYR97 TYR390 and c) which are also able to form a Van der Waals interaction with a lipophilic binding region of a binding pocket such that one or more heavy atoms of the said compounds lie within a 5 Å range of any of the heavy atoms of the following bromodomain residues which define the binding pocket: BRD-2 BRD-2 BRD-3 BRD-4 BRD-4 BD1 BD2 BD1 BRD-3 BD2 BD1 BD2 TRP97 TRP370 TRP57 TRP332 TRP81 TRP374 PRO98 PRO371 PRO58 PRO333 PRO82 PRO375 ASP161 ASP434 ASP121 GLU396 ASP145 GLU438 ILE162 VAL435 ILE122 VAL397 ILE146 VAL439 MET165 MET438 MET125 MET400 MET149 MET442 pharmaceutical compositions containing such compounds, and their use in therapy.

  一种用于鉴定分子量在100至750范围内的化合物，其抑制人类BRD-2至4的第一和/或第二溴代域与其生理伴侣蛋白的乙酰化赖氨酸残基的结合的方法，包括选择那些能够：a）形成氢键相互作用，其中化合物接受BRD-2、BRD-3、BRD-4、BD1、BD2中天冬氨酸残基侧链NH2基团的氢键，位置分别为：BRD-2 ASN156、BRD-2 ASN429、BRD-3 ASN116、BRD-4 ASN391、BRD-4 ASN140、BRD-4 ASN433；或b）接受水介导的氢键，其中化合物接受与BRD-2、BRD-3、BRD-4、BD1、BD2中酪氨酸残基侧链羟基相互作用的水的氢键，位置分别为：BRD-2 TYR113、BRD-3 TYR386、BRD-4 TYR73、BRD-4 TYR348、BRD-4 TYR97、BRD-4 TYR390；并且c）也能够在结合口袋的疏水结合区域中形成范德华相互作用，使得所述化合物的一个或多个重原子位于以下溴代域残基的任何重原子的5Å范围内，从而定义结合口袋：BRD-2、BRD-3、BRD-4、BD1、BD2中的TRP97、TRP370、TRP57、TRP332、TRP81、TRP374、PRO98、PRO371、PRO58、PRO333、PRO82、PRO375、ASP161、ASP434、ASP121、GLU396、ASP145、GLU438、ILE162、VAL435、ILE122、VAL397、ILE146、VAL439、MET165、MET438、MET125、MET400、MET149、MET442。还涉及含有这种化合物的制药组合物以及它们在治疗中的用途。