8-bromo-N-methyl-1,6-naphthyridine-2-carboxamide | 875514-91-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 8-bromo-N-methyl-1,6-naphthyridine-2-carboxamide
• 英文别名: 8-Bromo-[1,6]naphthyridine-2-carboxylic acid methylamide
• CAS: 875514-91-3
• 化学式: C₁₀H₈BrN₃O
• 分子量: 266.097
• InChiKey: CXXAZTBJANEUQL-UHFFFAOYSA-N

物化性质

• 沸点：
  502.9±45.0 °C(Predicted)
• 密度：
  1.597±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  54.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  8-bromo-N-methyl-1,6-naphthyridine-2-carboxamide 在 potassium phosphate 、 [1,1’-bis(di-tert-butylphosphino)ferrocene]dichloropalladium(Il) 、 间氯过氧苯甲酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 45.0h， 生成 8-(2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)phenyl)-2-(methylcarbamoyl)-1,6-naphthyridine-6-oxide
  参考文献：
  名称：

  NOVEL NAPHTHYRIDINES AND ISOQUINOLINES AND THEIR USE AS CDK8/19 INHIBITORS

  摘要：

  本发明涉及萘啶和异喹啉化合物，以及由此组成的药物可接受的组合物，作为CDK8/19的抑制剂，用于治疗与CDK8/19相关疾病。

  公开号：

  US20160016951A1
• 作为产物：
  描述：

  甲胺 、 8-溴-3-甲基-[1,6]萘啶-2-羧酸 在 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 、 四氢呋喃 为溶剂， 反应 18.42h， 以97%的产率得到8-bromo-N-methyl-1,6-naphthyridine-2-carboxamide
  参考文献：
  名称：

  NOVEL NAPHTHYRIDINES AND ISOQUINOLINES AND THEIR USE AS CDK8/19 INHIBITORS

  摘要：

  本发明涉及萘啶和异喹啉化合物，以及由此组成的药物可接受的组合物，作为CDK8/19的抑制剂，用于治疗与CDK8/19相关疾病。

  公开号：

  US20160016951A1

文献信息

• 2,8-Disubstituted naphthyridine derivatives
  申请人：Hanson J. Gunnar

  公开号：US20060030584A1

  公开（公告）日：2006-02-09

  Disclosed are compounds of formula A: and pharmaceutically acceptable salts thereof, wherein R 1 , R 2 , R 2 ′, R 3 , R 21 , A 1 , A 2 , X, and Z are as defined herein. Compounds of formula A are useful in the treatment of diseases and/or conditions related to cell differentiation, such as cancer, inflammation, arthritis, angiogenesis, or the like. Also disclosed are pharmaceutical compositions comprising compounds of the invention and methods of treating the aforementioned conditions using such compounds.

  揭示了公式A的化合物及其药学上可接受的盐，其中R1、R2、R2′、R3、R21、A1、A2、X和Z如本文所定义。公式A的化合物在治疗与细胞分化相关的疾病和/或症状方面具有用途，如癌症、炎症、关节炎、血管生成等。还披露了包含本发明化合物的药物组合物和使用这些化合物治疗上述症状的方法。
• 2, 8-disubstituted Naphthyridine Derivatives
  申请人：Hanson J. Gunnar

  公开号：US20080032991A1

  公开（公告）日：2008-02-07

  Disclosed are compounds of formula A: and pharmaceutically acceptable salts thereof, wherein R 1 , R 2 , R 2 ′, R 3 , R 21 , A 1 , A 2 , X, and Z are as defined herein. Compounds of formula A are useful in the treatment of diseases and/or conditions related to cell differentiation, such as cancer, inflammation, arthritis, angiogenesis, or the like. Also disclosed are pharmaceutical compositions comprising compounds of the invention and methods of treating the aforementioned conditions using such compounds.

  本发明揭示了A式化合物及其药学上可接受的盐，其中R1、R2、R2′、R3、R21、A1、A2、X和Z的定义如本文所述。A式化合物在治疗与细胞分化相关的疾病和/或病况（如癌症、炎症、关节炎、血管生成等）方面具有用途。此外，本发明还揭示了包含所述化合物的制药组合物和使用这些化合物治疗上述病况的方法。
• 2,8-Disubstituted-1,6-Naphthyridines and 4,6-Disubstituted-Isoquinolines with Potent, Selective Affinity for CDK8/19
  作者：Aurélie Mallinger、Kai Schiemann、Christian Rink、Jimmy Sejberg、Mark A. Honey、Paul Czodrowski、Mark Stubbs、Oliver Poeschke、Michael Busch、Richard Schneider、Daniel Schwarz、Djordje Musil、Rosemary Burke、Klaus Urbahns、Paul Workman、Dirk Wienke、Paul A. Clarke、Florence I. Raynaud、Suzanne A. Eccles、Christina Esdar、Felix Rohdich、Julian Blagg

  DOI：10.1021/acsmedchemlett.6b00022

  日期：2016.6.9

  We demonstrate a designed scaffold-hop approach to the discovery of 2,8-disubstituted-1,6-naphthyridine- and 4,6-disubstituted-isoquinoline-based dual CDK8/19 ligands. Optimized compounds in both series exhibited rapid aldehyde oxidase-mediated metabolism, which could be abrogated by introduction of an amino substituent at C5 of the 1,6-naphthyridine scaffold or at C1 of the isoquinoline scaffold. Compounds 51 and 59 were progressed to in vivo pharmacokinetic studies, and 51 also demonstrated sustained inhibition of STAT1(SER727) phosphorylation, a biomarker of CDK8 inhibition, in an SW620 colorectal carcinoma human tumor xenograft model following oral dosing.
• Ergosterol analogs as inhibitors of cyclin dependent kinase 8
  作者：Petros D. Siapkaras、Eirik Johansson Solum

  DOI：10.1016/j.steroids.2022.108965

  日期：2022.2
• NOVEL NAPHTHRYIDINES AND ISOQUINOLINES AND THEIR USE AS CDK8/19 INHIBITORS
  申请人：Merck Patent GmbH

  公开号：EP3169678A1

  公开（公告）日：2017-05-24