1-methyl-4H,6H-benzo[e][1,2,4]triazolo[3,4-c][1,4]oxazepine

• 分子结构分类: 有机化合物 - 苯类化合物
• 英文名称: 1-methyl-4H,6H-benzo[e][1,2,4]triazolo[3,4-c][1,4]oxazepine
• 英文别名: 1-Methyl-4h,6h-[1,2,4]triazolo[4,3-A][4,1]benzoxazepine；1-methyl-4,6-dihydro-[1,2,4]triazolo[4,3-a][4,1]benzoxazepine
• 化学式: C₁₁H₁₁N₃O
• 分子量: 201.228
• InChiKey: HEEIZXCFEVISIX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  39.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1,5-dihydrobenzo[e][1,4]oxazepin-2(3H)-one 在 劳森试剂 作用下， 以 正丁醇 为溶剂， 反应 101.0h， 生成 1-methyl-4H,6H-benzo[e][1,2,4]triazolo[3,4-c][1,4]oxazepine
  参考文献：
  名称：

  SETDB1 Tudor域的第一个片段命中的鉴定和表征。

  摘要：

  SET域分叉蛋白1（SETDB1）是一种人类组蛋白赖氨酸甲基转移酶，在人类癌症中被扩增，并且被证明对非小细胞肺癌和小细胞肺癌的生长至关重要。除其催化结构域外，SETDB1还具有独特的串联都铎结构域，该结构可识别同时含有甲基化和乙酰化赖氨酸的组蛋白序列，并可能有助于其在染色质上的定位。使用X射线晶体学和NMR光谱片段筛选方法，我们确定了第一个与SETDB1的串联Tudor域（TTD）的组蛋白肽结合槽结合的小分子片段。在本文中，我们描述了这些片段和类似物的结合模式以及关键化合物的生物物理特性。

  DOI：

  10.1016/j.bmc.2019.07.020

文献信息

• [EN] FUSED 1,4-OXAZEPINES AND RELATED ANALOGS AS BET BROMODOMAIN INHIBITORS<br/>[FR] 1,4-OXAZEPINES CONDENSÉES ET LEURS ANALOGUES ASSOCIÉS EN TANT QU'INHIBITEURS DE BROMODOMAINE BET
  申请人：UNIV MICHIGAN REGENTS

  公开号：WO2017142881A1

  公开（公告）日：2017-08-24

  The present disclosure provides fused 1,4-oxazepines and related analogs represented by Formula (I) and the pharmaceutically acceptable salts, hydrates, and solvates thereof, wherein R1, R2a, R2b, R3a, R3b, R4, R5, A, and Y are as defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula (I) to treat a condition or disorder responsive to inhibition of BET bromodomains such as cancer.

  本发明公开了式(I)表示的融合1,4-噁嗪和相关类似物及其药学上可接受的盐、水合物和溶剂化物，其中R1、R2a、R2b、R3a、R3b、R4、R5、A和Y的定义如说明书中所述。本发明还涉及式(I)化合物用于治疗对BET溴结构域抑制有反应的病症或疾病，如癌症的用途。
• Compounds useful in therapy
  申请人：Ryckmans Thomas

  公开号：US20070167430A1

  公开（公告）日：2007-07-19

  Compounds of formula (I), or a pharmaceutically acceptable derivative thereof, wherein: X represents NR or O; R represents hydrogen, C 1-8 alkyl or SO 2 └C, 1-8 alkyl┘; W represents N or CH; Y and Y′ independently represent hydrogen, halogen, OH, CF 3 , OCF 3 , CN, NH 2 C 1-8 alkyl, C 1-8 alkyloxy or C 3-8 cycloalkyl; Ring A represents a heterocyclic ring containing at least one nitrogen atom; Z represents a direct link, C 1-8 alkyl or C 3-8 cycloalkyl; R 1 represents R 2 , OR 2 , OR 3 —R 4 , N(R 2 )[C 1-8 alkylene] a R 4 ; NCOR 2 , or SR 4 ; R 2 and R 4 independently represent hydrogen, C 3-8 cycloalkyl, CF 3 , Ar or Het; R 3 represents a direct link or C 1-8 alkyl; is 0 or 1; Ar represents an aromatic ring, optionally fused to a heterocyclic ring, and/or optionally substituted with one or more groups as described below; Het represents a heterocyclic ring optionally substituted with one or more groups as described below, and/or optionally fused to an aromatic ring which is optionally substituted with one or more groups as described below; at each occurrence C 1-8 alkyl, C 1-8 alkylene and C 3-8 cycloalkyl may be independently optionally substituted with one or more groups as described below; substituent groups for Ar, Het, C 1-8 alkyl, C 1-8 alkylene and C 3-8 cycloalkyl referred to the above are independently selected from hydrogen, halogen, C 1-8 alkyl, C 1-8 alkyloxy, S[C 1-8 alkyl], CN, CF 3 , NH 2 and OH; are useful for treating anxiety, cardiovascular disease (including angina, atherosclerosis, hypertension, heart failure, edema, hypernatremia), dysmenorrhoea (primary and secondary), endometriosis, emesis (including motion sickness), intrauterine growth retardation, inflammation (including rheumatoid arthritis), mittelschmerz, preclampsia, premature ejaculation, premature (preterm) labor and Raynaud's disease.

  化合物的式子（I），或其药学上可接受的衍生物，其中：X代表NR或O; R代表氢，C1-8烷基或SO2└C，1-8烷基┘; W代表N或CH; Y和Y′分别代表氢，卤素，OH，CF3，O ，CN，NH2C1-8烷基，C1-8烷氧基或C3-8环烷基; 环A表示至少含有一个氮原子的杂环; Z表示直接连接，C1-8烷基或C3-8环烷基; R1表示R2，OR2，OR3—R4，N（R2）[C1-8烷基]aR4; NCOR2，或SR4; R2和R4分别表示氢，C3-8环烷基， ，Ar或Het; R3表示直接连接或C1-8烷基; 为0或1; Ar表示芳香环，可选地与杂环融合，并/或可选地用下述一种或多种基团进行取代; Het表示杂环，可选地用下述一种或多种基团进行取代，并/或可选地与可选地用下述一种或多种基团进行取代的芳香环融合; 在每次出现中，C1-8烷基，C1-8烷基和C3-8环烷基可以独立地用下述一种或多种基团进行取代; 上述Ar，Het，C1-8烷基，C1-8烷基和C3-8环烷基的取代基团是独立选择的，包括氢，卤素，C1-8烷基，C1-8烷氧基，S[C1-8烷基]，CN， ，NH2和OH; 用于治疗焦虑症，心血管疾病（包括心绞痛，动脉粥样硬化，高血压，心力衰竭，水肿，高钠血症），痛经（原发性和继发性），子宫内膜异位症，呕吐（包括晕动病），宫内生长迟缓，炎症（包括类风湿性关节炎），中间痛，先兆子痫，早泄，早产和雷诺病。
• FUSED 1,4-OXAZEPINES AND RELATED ANALOGS AS BET BROMODOMAIN INHIBITORS
  申请人：THE REGENTS OF THE UNIVERSITY OF MICHIGAN

  公开号：US20210188870A1

  公开（公告）日：2021-06-24

  The present disclosure provides fused 1,4-oxazepines and related analogs represented by Formula (I) and the pharmaceutically acceptable salts, hydrates, and solvates thereof, wherein R 1 , R 2a , R 2b , R 3a , R 3b , R 4 , R 5 , A, and Y are as defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula (I) to treat a condition or disorder responsive to inhibition of BET bromodomains such as cancer.