{5-[3-(5-Piperidin-1-ylmethyl-1H-indol-2-yl)-1H-indazol-6-yl]-1H-[1,2,3]triazol-4-yl}-methanol | 905998-48-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: {5-[3-(5-Piperidin-1-ylmethyl-1H-indol-2-yl)-1H-indazol-6-yl]-1H-[1,2,3]triazol-4-yl}-methanol
• 英文别名: (5-{3-[5-(Piperidin-1-Ylmethyl)-1h-Indol-2-Yl]-1h-Indazol-6-Yl}-2h-1,2,3-Triazol-4-Yl)methanol；[5-[3-[5-(piperidin-1-ylmethyl)-1H-indol-2-yl]-1H-indazol-6-yl]-2H-triazol-4-yl]methanol
• CAS: 905998-48-3
• 化学式: C₂₄H₂₅N₇O
• 分子量: 427.509
• InChiKey: FNWHPLLNMLOZTL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  110
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-[3-(5-Piperidin-1-ylmethyl-1H-indol-2-yl)-1H-indazol-6-yl]-1H-[1,2,3]triazole-4-carbaldehyde 在 sodium tetrahydroborate 作用下， 生成 {5-[3-(5-Piperidin-1-ylmethyl-1H-indol-2-yl)-1H-indazol-6-yl]-1H-[1,2,3]triazol-4-yl}-methanol
  参考文献：
  名称：

  3-(Indol-2-yl)indazoles as Chek1 kinase inhibitors: Optimization of potency and selectivity via substitution at C6

  摘要：

  The development of 3-(indol-2-yl)indazoles as inhibitors of Chek1 kinase is described. Introduction of amides and heteroaryl groups at the C6 position of the indazole ring system provided sufficient Chek1 potency and selectivity over Cdk7 to permit escape from DNA damage-induced arrest in a cellular assay. Enzyme potency against Chek1 was optimized by the incorporation of a hydroxymethyl triazole moiety in compound 21 (Chek1 IC(50)=0.30nM) that was shown by X-ray crystallography to displace one of three highly conserved water molecules in the HI region of the ATP-binding cleft.

  DOI：

  10.1016/j.bmcl.2006.08.118

文献信息

• Inhibitors of Checkpoint Kinases
  申请人：Arrington L. Kenneth

  公开号：US20080004259A1

  公开（公告）日：2008-01-03

  The instant invention provides for compounds which comprise substituted indolyl indazoles that inhibit CHK1 activity. The instant compounds provide a novel mechanism of action with unexpected advantageous properties; such unexpected advantageous properties may include increased cellular potency/solubility, greater selectivity, enhanced pharmacokinetic properties, lack of off target activity and so on. The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting CHK1 activity by administering the compound to a patient in need of treatment of cancer.

  本发明提供了一种包括取代的吲哚基吲唑化合物，能够抑制CHK1活性。这些化合物提供了一种新的作用机制，具有意想不到的优越性质；这些意想不到的优越性质可能包括增强的细胞效力/溶解度、更高的选择性、增强的药代动力学性质、缺乏非靶标活性等等。本发明还提供了包含这些抑制剂化合物的组合物以及通过向需要治疗癌症的患者投药来抑制CHK1活性的方法。
• INHIBITORS OF CHECKPOINT KINASES
  申请人：Merck & Co., Inc.

  公开号：EP1851203A2

  公开（公告）日：2007-11-07
• IDENTIFICATION AND TARGETED MODULATION OF GENE SIGNALING NETWORKS
  申请人：CAMP4 THERAPEUTICS CORPORATION

  公开号：US20210254056A1

  公开（公告）日：2021-08-19

  The present invention provides methods and compositions for the evaluation, alteration and/or optimization of gene signaling. Methods and systems are also provided which exploit the information generated in the identification of new targets and non-canonical signaling pathways.
• [EN] INHIBITORS OF CHECKPOINT KINASES<br/>[FR] INHIBITEURS DE KINASES DE CONTROLE
  申请人：MERCK & CO INC

  公开号：WO2006086255A2

  公开（公告）日：2006-08-17

  [EN] The instant invention provides for compounds which comprise substituted indolyl indazoles that inhibit CHK1 activity. The instant compounds provide a novel mechanism of action with unexpected advantageous properties; such unexpected advantageous properties may include increased cellular potency/solubility, greater selectivity, enhanced pharmacokinetic properties, lack of off target activity and so on. The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting CHK1 activity by administering the compound to a patient in need of treatment of cancer.
  [FR] L'invention se rapporte à des composés contenant des indazoles d'indolyl substitués qui inhibent l'activité de CHK1. Ces composés fournissent un nouveau mécanisme d'action présentant des propriétés avantageuses inédites ; ces propriétés avantageuses inédites comprenant une meilleure puissance/solubilité cellulaire, une meilleure sélectivité, des propriétés pharmacocinétiques améliorées, un manque d'activité hors cible etc. Cette invention se rapporte aussi à des compositions contenant ces composés inhibiteurs et à des procédés d'inhibition de l'activité de CHK1 par administration du composé à un patient qui doit recevoir un traitement contre le cancer.
• 3-(Indol-2-yl)indazoles as Chek1 kinase inhibitors: Optimization of potency and selectivity via substitution at C6
  作者：Mark E. Fraley、Justin T. Steen、Edward J. Brnardic、Kenneth L. Arrington、Keith L. Spencer、Barbara A. Hanney、Yuntae Kim、George D. Hartman、Steven M. Stirdivant、Bob A. Drakas、Keith Rickert、Eileen S. Walsh、Kelly Hamilton、Carolyn A. Buser、James Hardwick、Weikang Tao、Stephen C. Beck、Xianzhi Mao、Robert B. Lobell、Laura Sepp-Lorenzino、Youwei Yan、Mari Ikuta、Sanjeev K. Munshi、Lawrence C. Kuo、Constantine Kreatsoulas

  DOI：10.1016/j.bmcl.2006.08.118

  日期：2006.12

  The development of 3-(indol-2-yl)indazoles as inhibitors of Chek1 kinase is described. Introduction of amides and heteroaryl groups at the C6 position of the indazole ring system provided sufficient Chek1 potency and selectivity over Cdk7 to permit escape from DNA damage-induced arrest in a cellular assay. Enzyme potency against Chek1 was optimized by the incorporation of a hydroxymethyl triazole moiety in compound 21 (Chek1 IC(50)=0.30nM) that was shown by X-ray crystallography to displace one of three highly conserved water molecules in the HI region of the ATP-binding cleft.