N-(6-{6-chloro-5-[(phenylsulfonyl)methyl]-3-pyridinyl}-1H-indazol-4-yl)-2-methyl-1,3-thiazole-4-carboxamide | 1309778-62-8

• 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: N-(6-{6-chloro-5-[(phenylsulfonyl)methyl]-3-pyridinyl}-1H-indazol-4-yl)-2-methyl-1,3-thiazole-4-carboxamide
• 英文别名: N-[6-[5-(benzenesulfonylmethyl)-6-chloropyridin-3-yl]-1H-indazol-4-yl]-2-methyl-1,3-thiazole-4-carboxamide
• CAS: 1309778-62-8
• 化学式: C₂₄H₁₈ClN₅O₃S₂
• 分子量: 524.024
• InChiKey: UVXHWBWTIFPAKH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  35
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  154
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-硝基-6-溴-1H-吲唑 在 吡啶 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium acetate 、 铁粉 、 sodium carbonate 、 氯化铵 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 6.33h， 生成 N-(6-{6-chloro-5-[(phenylsulfonyl)methyl]-3-pyridinyl}-1H-indazol-4-yl)-2-methyl-1,3-thiazole-4-carboxamide
  参考文献：
  名称：

  Optimization of Novel Indazoles as Highly Potent and Selective Inhibitors of Phosphoinositide 3-Kinase δ for the Treatment of Respiratory Disease

  摘要：

  Optimization of lead compound 1, through extensive use of structure-based design and a focus on PI3K delta potency, isoform selectivity, and inhaled PK properties, led to the discovery of clinical candidates 2 (GSK2269557) and 3 (G5K2292767) for the treatment of respiratory indications via inhalation. Compounds 2 and 3 are both highly selective for PI3K delta over the closely related isoforms and are active in a disease relevant brown Norway rat acute OVA model of Th2-driven lung inflammation.

  DOI：

  10.1021/acs.jmedchem.5b00767

文献信息

• [EN] INDAZOLE DERIVATIVES AS PI 3 - KINASE INHIBITORS<br/>[FR] DÉRIVÉS D'INDAZOLE COMME INHIBITEURS DES PI3-KINASES
  申请人：GLAXO GROUP LTD

  公开号：WO2011067366A1

  公开（公告）日：2011-06-09

  The invention is directed to certain novel compounds. Specifically, the invention is directed to compounds of formula (I) and salts thereof. The compounds of the invention are inhibitors of PI3-kinase activity.

  这项发明涉及某些新颖化合物。具体而言，该发明涉及具有化学式(I)及其盐的化合物。该发明的化合物是PI3-激酶活性的抑制剂。
• INDAZOLE DERIVATIVES AS PI 3-KINASE
  申请人：Baldwin Ian Robert

  公开号：US20120238571A1

  公开（公告）日：2012-09-20

  The invention is directed to certain novel compounds. Specifically, the invention is directed to compounds of formula (I): and salts thereof. The compounds of the invention are inhibitors of PI3-kinase activity.

  本发明涉及某些新型化合物。具体而言，本发明涉及公式（I）的化合物及其盐。本发明的化合物是PI3-激酶活性抑制剂。
• INDAZOLE DERIVATIVES AS PI 3 - KINASE INHIBITORS
  申请人：Glaxo Group Limited

  公开号：EP2507231A1

  公开（公告）日：2012-10-10
• Optimization of Novel Indazoles as Highly Potent and Selective Inhibitors of Phosphoinositide 3-Kinase δ for the Treatment of Respiratory Disease
  作者：Kenneth Down、Augustin Amour、Ian R. Baldwin、Anthony W. J. Cooper、Angela M. Deakin、Leigh M. Felton、Stephen B. Guntrip、Charlotte Hardy、Zoë A. Harrison、Katherine L. Jones、Paul Jones、Suzanne E. Keeling、Joelle Le、Stefano Livia、Fiona Lucas、Christopher J. Lunniss、Nigel J. Parr、Ed Robinson、Paul Rowland、Sarah Smith、Daniel A. Thomas、Giovanni Vitulli、Yoshiaki Washio、J. Nicole Hamblin

  DOI：10.1021/acs.jmedchem.5b00767

  日期：2015.9.24

  Optimization of lead compound 1, through extensive use of structure-based design and a focus on PI3K delta potency, isoform selectivity, and inhaled PK properties, led to the discovery of clinical candidates 2 (GSK2269557) and 3 (G5K2292767) for the treatment of respiratory indications via inhalation. Compounds 2 and 3 are both highly selective for PI3K delta over the closely related isoforms and are active in a disease relevant brown Norway rat acute OVA model of Th2-driven lung inflammation.