4-bromo-5-(trifluoromethyl)-1H-indazole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: 4-bromo-5-(trifluoromethyl)-1H-indazole
• 英文别名: 4-Bromo-5-(trifluoromethyl)-1H-indazole
• 化学式: C₈H₄BrF₃N₂
• 分子量: 265.032
• InChiKey: TUTWVEKYKXGGIB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  28.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-bromo-5-(trifluoromethyl)-1H-indazole 在 tris-(dibenzylideneacetone)dipalladium(0) 、 caesium carbonate 、 对甲苯磺酸 、 2-二环己基磷-2',6'-二异丙氧基-1,1'-联苯 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 14.0h， 生成 (S)-2-((1-methylpyrrolidin-2-yl)methoxy)-4-(piperazin-1-yl)-7-(5-(trifluoromethyl)-1H-indazol-4-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine bis-TFA salt
  参考文献：
  名称：

  Identification of the Clinical Development Candidate MRTX849, a Covalent KRAS^G12C Inhibitor for the Treatment of Cancer

  摘要：

  Capping off an era marred by drug development failures and punctuated by waning interest and presumed intractability toward direct targeting of KRAS, new technologies and strategies are aiding in the target's resurgence. As previously reported, the tetrahydropyridopyrimidines were identified as irreversible covalent inhibitors of KRAS(G12C) that bind in the switch-II pocket of KRAS and make a covalent bond to cysteine 12. Using structure-based drug design in conjunction with a focused in vitro absorption, distribution, metabolism and excretion screening approach, analogues were synthesized to increase the potency and reduce metabolic liabilities of this series. The discovery of the clinical development candidate MRTX849 as a potent, selective covalent inhibitor of KRAS(G12C) is described.

  DOI：

  10.1021/acs.jmedchem.9b02052

文献信息

• [EN] KRAS G12C INHIBITORS<br/>[FR] INHIBITEURS DE KRAS G12C
  申请人：MIRATI THERAPEUTICS INC

  公开号：WO2017201161A1

  公开（公告）日：2017-11-23

  The present invention relates to compounds that inhibit KRas G12C. In particular, the present invention relates to compounds that irreversibly inhibit the activity of KRas G12C, pharmaceutical compositions comprising the compounds and methods of use therefor.

  本发明涉及抑制KRas G12C的化合物。特别是，本发明涉及不可逆地抑制KRas G12C活性的化合物，包括含有这些化合物的药物组合物及其使用方法。
• KRAS G12C INHIBITORS
  申请人：Mirati Therapeutics, Inc.

  公开号：US20190144444A1

  公开（公告）日：2019-05-16

  The present invention relates to compounds that inhibit KRas G12C. In particular, the present invention relates to compounds that irreversibly inhibit the activity of KRas G12C, pharmaceutical compositions comprising the compounds and methods of use therefor.

  本发明涉及抑制KRas G12C的化合物。特别地，本发明涉及不可逆抑制KRas G12C活性的化合物、包含这些化合物的药物组合物及其使用方法。
• [EN] IMIDAZOTRIAZINE AND PYRROLOPYRIMIDINE DERIVATIVES AS KRAS G12C INHIBITORS<br/>[FR] DÉRIVÉS D'IMIDAZOTRIAZINE ET DE PYRROLOPYRIMIDINE UTILISÉS COMME INHIBITEURS DE KRAS G12C
  申请人：BEIGENE LTD

  公开号：WO2022028492A1

  公开（公告）日：2022-02-10

  Disclosed herein are imidazotriazine and pyrrolopyrimidine derivatives or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof useful as a G12C inhibitors, and a pharmaceutical composition comprising the same. Also disclosed herein is the use in manufacture of medicaments for treating cancer using the imidazotriazine and pyrrolopyrimidine derivatives or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof as G12C inhibitors.

  本文披露了咪唑三嗪和吡咯吡嘧啶衍生物或其立体异构体，或其药学上可接受的盐，其作为G12C抑制剂的有用性，以及包含它们的药物组合物。本文还披露了使用咪唑三嗪和吡咯吡嘧啶衍生物或其立体异构体，或其药学上可接受的盐作为G12C抑制剂制造药物治疗癌症的用途。
• KRas G12C inhibitors
  申请人：Mirati Therapeutics, Inc.

  公开号：US10125134B2

  公开（公告）日：2018-11-13

  The present invention relates to compounds that inhibit KRas G12C. In particular, the present invention relates to compounds that irreversibly inhibit the activity of KRas G12C, pharmaceutical compositions comprising the compounds and methods of use therefor.

  本发明涉及抑制 KRas G12C 的化合物。特别是，本发明涉及不可逆地抑制 KRas G12C 活性的化合物、包含该化合物的药物组合物及其使用方法。
• KRAS G12C inhibitors
  申请人：Mirati Therapeutics, Inc.

  公开号：US11267812B2

  公开（公告）日：2022-03-08

  The present invention relates to compounds that inhibit KRas G12C. In particular, the present invention relates to compounds that irreversibly inhibit the activity of KRas G12C, pharmaceutical compositions comprising the compounds and methods of use therefor.

  本发明涉及抑制 KRas G12C 的化合物。特别是，本发明涉及不可逆地抑制 KRas G12C 活性的化合物、包含该化合物的药物组合物及其使用方法。