1-methyl-4,5,6,7-tetrahydro-1H-indazol-3-amine | 26396-84-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 亚胺内酰胺
• 英文名称: 1-methyl-4,5,6,7-tetrahydro-1H-indazol-3-amine
• 英文别名: 1-Methyl-4,5,6,7-tetrahydro-1H-indazol-3-amine；1-methyl-4,5,6,7-tetrahydroindazol-3-amine
• CAS: 26396-84-9
• 化学式: C₈H₁₃N₃
• 分子量: 151.211
• InChiKey: UZOLRYXTOQMICT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  43.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-(4-chloro-6-methoxy-2-methyl-9H-pyrimido[4,5-b]indol-7-yl)-3,5-dimethylisoxazole 、 1-methyl-4,5,6,7-tetrahydro-1H-indazol-3-amine 、 三氟乙酸 在 potassium phosphate 、 tris-(dibenzylideneacetone)dipalladium(0) 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 作用下， 以 甲苯 、 水 、 乙腈 为溶剂， 以100 mg的产率得到7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-2-methyl-N-(1-methyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-9H-pyrimido[4,5-b]indol-4-amine trifluoroacetate
  参考文献：
  名称：

  CF53作为强效和口服生物可用的溴结构域和末端（BET）溴结构域抑制剂的基于结构的发现

  摘要：

  我们报告基于结构的发现CF53（28）作为bromodomain和额外的终端（BET）蛋白质的高效和口服活性抑制剂。通过将NH-吡唑基团掺入9H-嘧啶并[4,5- b ]吲哚核中，我们鉴定了一系列与K i结合BRD4 BD1蛋白的化合物值小于1 nM，并且在白血病和乳腺癌细胞的细胞生长抑制中实现了低纳摩尔浓度的效价。最有前途的化合物CF53具有出色的口服药代动力学特性，并且在小鼠三阴性乳腺癌和急性白血病异种移植模型中均具有显着的抗肿瘤活性。CF53与BRD4 BD1蛋白的共晶体结构的确定为其对BET蛋白的高结合亲和力提供了结构基础。CF53对非BET含溴结构域的蛋白质具有很高的选择性。这些数据将CF53确立为一种有效的，选择性的和口服活性的BET抑制剂，因此有必要对先进的临床前开发进行进一步评估。

  DOI：

  10.1021/acs.jmedchem.8b00483
• 作为产物：
  描述：

  2-(N-Aethoxycarbonyl-thiocarbamoyl)-cyclohexanon-(1) 、 甲基肼 以 乙醇 为溶剂， 以0.22 g的产率得到1-methyl-4,5,6,7-tetrahydro-1H-indazol-3-amine
  参考文献：
  名称：

  9H-PYRIMIDO[4,5-B]INDOLES AND RELATED ANALOGS AS BET BROMODOMAIN INHIBITORS

  摘要：

  本公开提供了代表为式I的替代的9H-嘧啶并[4,5-b]吲哚和5H-吡啶并[4,3-b]吲哚及相关类似物的药用可接受的盐、水合物和溶剂合物，其中R1a、A、B1、B2、G、X1、Y1、Y2和Y3如规范中所定义。本公开还涉及使用式I的化合物来治疗对BET溴结构域抑制敏感的状况或疾病。本公开的化合物特别适用于治疗癌症。

  公开号：

  US20150246923A1

文献信息

• 9H-pyrimido [4,5-b]indoles and related analogs as BET bromodomain inhibitors
  申请人：THE REGENTS OF THE UNIVERSITY OF MICHIGAN

  公开号：US10253044B2

  公开（公告）日：2019-04-09

  The present disclosure provides substituted 9H-pyrimido[4,5-b]indoles and 5H-pyrido[4,3-b]indoles and related analogs represented by Formula I: and the pharmaceutically acceptable salts, hydrates, and solvates thereof, wherein R1a, A, B1, B2, G, X1, Y1, Y2, and Y3 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. Compounds of the present disclosure are especially useful for treating cancer.

  本公开提供了由式 I 表示的取代的 9H-嘧啶并[4,5-b]吲哚和 5H-嘧啶并[4,3-b]吲哚及相关类似物： 及其药学上可接受的盐、水合物和溶液，其中 R1a、A、B1、B2、G、X1、Y1、Y2 和 Y3 如说明书中所定义。本公开还涉及使用式 I 的化合物治疗对抑制 BET 溴链有反应的病症或紊乱。本公开的化合物特别适用于治疗癌症。
• 9H-PYRIMIDO [4,5-B]INDOLES AND RELATED ANALOGS AS BET BROMODOMAIN INHIBITORS
  申请人：THE REGENTS OF THE UNIVERSITY OF MICHIGAN

  公开号：US20170210761A1

  公开（公告）日：2017-07-27

  The present disclosure provides substituted 9H-pyrimido[4,5-b]indoles and 5H-pyrido[4,3-b]indoles and related analogs represented by Formula I: and the pharmaceutically acceptable salts, hydrates, and solvates thereof, wherein R 1a , A, B 1 , B 2 , G, X 1 , Y 1 , Y 2 , and Y 3 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. Compounds of the present disclosure are especially useful for treating cancer.
• US9580430B2
  申请人：——

  公开号：US9580430B2

  公开（公告）日：2017-02-28
• [EN] 9H-PYRIMIDO[4,5-B]INDOLES AND RELATED ANALOGS AS BET BROMODOMAIN INHIBITORS<br/>[FR] 9H-PYRIMIDO[4,5-B]INDOLES ET LEURS ANALOGUES ASSOCIÉS COMME INHIBITEURS DE BROMODOMAINE BET
  申请人：UNIV MICHIGAN

  公开号：WO2015131005A1

  公开（公告）日：2015-09-03

  The present disclosure provides substituted 9H-pyrimido[4,5-b]indoles and 5H-pyrido[4,3-b]indoles and related analogs represented by Formula (I) and the pharmaceutically acceptable salts, hydrates, and solvates thereof, wherein R1a, A, B1, B2, G, X1, Y1, Y2, and Y3 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. Compounds of the present disclosure are especially useful for treating cancer.
• 9H-PYRIMIDO[4,5-B]INDOLES AND RELATED ANALOGS AS BET BROMODOMAIN INHIBITORS
  申请人：THE REGENTS OF THE UNIVERSITY OF MICHIGAN

  公开号：US20150246923A1

  公开（公告）日：2015-09-03

  The present disclosure provides substituted 9H-pyrimido[4,5-b]indoles and 5H-pyrido[4,3-b]indoles and related analogs represented by Formula I: and the pharmaceutically acceptable salts, hydrates, and solvates thereof, wherein R 1a , A, B 1 , B 2 , G, X 1 , Y 1 , Y 2 , and Y 3 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. Compounds of the present disclosure are especially useful for treating cancer.

  本公开提供了代表为式I的替代的9H-嘧啶并[4,5-b]吲哚和5H-吡啶并[4,3-b]吲哚及相关类似物的药用可接受的盐、水合物和溶剂合物，其中R1a、A、B1、B2、G、X1、Y1、Y2和Y3如规范中所定义。本公开还涉及使用式I的化合物来治疗对BET溴结构域抑制敏感的状况或疾病。本公开的化合物特别适用于治疗癌症。