1-(6-bromo-2-pyridyl)-6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridine | 1527525-86-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 1-(6-bromo-2-pyridyl)-6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridine
• 英文别名: 1-(6-bromopyridin-2-yl)-6-(6-methylpyrazin-2-yl)-1H-pyrazolo[4,3-c]pyridine；1-(6-Bromo-2-pyridyl)-6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridine；1-(6-bromopyridin-2-yl)-6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridine
• CAS: 1527525-86-5
• 化学式: C₁₆H₁₁BrN₆
• 分子量: 367.208
• InChiKey: KASCBXUNVMJRCA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  69.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(6-bromo-2-pyridyl)-6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridine 在 盐酸 、 三叔丁基膦 、 palladium diacetate 、 [双(2-甲氧基乙基)胺]三氟化硫 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 38.0h， 生成 (R)-1-(6-(4,4-difluoropiperidin-3-yl)pyridin-2-yl)-6-(6-methylpyrazin-2-yl)-1H-pyrazolo[4,3-c]pyridine
  参考文献：
  名称：

  Discovery of 5-Azaindazole (GNE-955) as a Potent Pan-Pim Inhibitor with Optimized Bioavailability

  摘要：

  Pim kinases have been identified as promising therapeutic targets for hematologic-oncology indications, including multiple myeloma and certain leukemia. Here, we describe our continued efforts in optimizing a lead series by improving bioavailability while maintaining high inhibitory potency against all three Pim kinase isoforms. The discovery of extensive intestinal metabolism and major metabolites helped refine our design strategy, and we observed that optimizing the pharmacokinetic properties first and potency second was a more successful approach than the reverse. In the resulting work, novel analogs such as 20 (GNE-955) were discovered bearing 5-azaindazole core with noncanonical hydrogen bonding to the hinge.

  DOI：

  10.1021/acs.jmedchem.7b00418
• 作为产物：
  描述：

  1-(tetrahydro-2H-pyran-2-yl)-6-(tributylstannyl)-1H-pyrazolo[4,3-c]pyridine 在 盐酸 、 tris-(dibenzylideneacetone)dipalladium(0) 、 caesium carbonate 、 三环己基膦 作用下， 以 1,4-二氧六环 、 N,N-二甲基乙酰胺 、 水 、 二甲基亚砜 为溶剂， 反应 36.0h， 生成 1-(6-bromo-2-pyridyl)-6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridine
  参考文献：
  名称：

  Discovery of 5-Azaindazole (GNE-955) as a Potent Pan-Pim Inhibitor with Optimized Bioavailability

  摘要：

  Pim kinases have been identified as promising therapeutic targets for hematologic-oncology indications, including multiple myeloma and certain leukemia. Here, we describe our continued efforts in optimizing a lead series by improving bioavailability while maintaining high inhibitory potency against all three Pim kinase isoforms. The discovery of extensive intestinal metabolism and major metabolites helped refine our design strategy, and we observed that optimizing the pharmacokinetic properties first and potency second was a more successful approach than the reverse. In the resulting work, novel analogs such as 20 (GNE-955) were discovered bearing 5-azaindazole core with noncanonical hydrogen bonding to the hinge.

  DOI：

  10.1021/acs.jmedchem.7b00418

文献信息

• [EN] 5-AZAINDAZOLE COMPOUNDS AND METHODS OF USE<br/>[FR] COMPOSÉS 5-AZAINDAZOLE ET MÉTHODES D'UTILISATION
  申请人：HOFFMANN LA ROCHE

  公开号：WO2014001377A1

  公开（公告）日：2014-01-03

  5-Azaindazole compounds of Formula (I), including stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof, are useful for inhibiting Pim kinase, and for treating disorders such as cancer mediated by Pim kinase. Methods of using compounds of Formula (I) for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

  公式（I）的5-氮杂吲唑化合物，包括立体异构体、几何异构体、互变异构体和其药学上可接受的盐，用于抑制Pim激酶，并用于治疗由Pim激酶介导的癌症等疾病。公开了使用公式（I）化合物在哺乳动物细胞中进行体外、体内和体内诊断、预防或治疗此类疾病或相关病理条件的方法。
• 5-AZAINDAZOLE COMPOUNDS AND METHODS OF USE
  申请人：Genentech, Inc.

  公开号：US20140005168A1

  公开（公告）日：2014-01-02

  5-Azaindazole compounds of Formula I, including stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof, are useful for inhibiting Pim kinase, and for treating disorders such as cancer mediated by Pim kinase. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

  公式I中的5-Azaindazole化合物，包括立体异构体、几何异构体、互变异构体和药学上可接受的盐，对于抑制Pim激酶和治疗由Pim激酶介导的癌症等疾病非常有用。本文揭示了使用公式I中的化合物在哺乳动物细胞中进行体外、体内和原位诊断、预防或治疗此类疾病或相关病理条件的方法。
• 5-azaindazole compounds and methods of use
  申请人：Genentech, Inc.

  公开号：US09434725B2

  公开（公告）日：2016-09-06

  5-Azaindazole compounds of Formula I, including stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof, are useful for inhibiting Pim kinase, and for treating disorders such as cancer mediated by Pim kinase. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

  式I的5-Azaindazole化合物，包括立体异构体、几何异构体、互变异构体和其药学上可接受的盐，对于抑制Pim激酶和治疗由Pim激酶介导的癌症等疾病具有用途。本文揭示了使用式I化合物进行哺乳动物细胞中的体外、原位和体内诊断、预防或治疗此类疾病或相关病理条件的方法。
• US9434725B2
  申请人：——

  公开号：US9434725B2

  公开（公告）日：2016-09-06