5-bromo-3-iodo-2-methylpyridine | 1211537-13-1

• 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: 5-bromo-3-iodo-2-methylpyridine
• 英文别名: 5-Bromo-3-iodo-2-methylpyridine
• CAS: 1211537-13-1
• 化学式: C₆H₅BrIN
• 分子量: 297.921
• InChiKey: YJGRBTUOBVMZQV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  9
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  12.9
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (3,5-二氟-4-羟基苯基)硼酸 、 5-bromo-3-iodo-2-methylpyridine 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 caesium carbonate 作用下， 以 乙醇 、 水 为溶剂， 反应 2.0h， 生成 4,4'-(2-methylpyridine-3,5-diyl)bis(2,6-difluorophenol)
  参考文献：
  名称：

  Development of Pyridine-based Inhibitors for the Human Vaccinia-related Kinases 1 and 2

  摘要：

  Vaccinia-related kinases 1 and 2 (VRK1 and VRK2) are human Ser/Thr protein kinases associated with increased cell division and neurological disorders. Nevertheless, the cellular functions of these proteins are not fully understood. Despite their therapeutic potential, there are no potent and specific inhibitors available for VRK1 or VRK2. We report here the discovery and elaboration of an aminopyridine scaffold as a basis for VRK1 and VRK2 inhibitors. The most potent compound for VRK1 (26) displayed an IC50 value of 150 nM and was fairly selective in a panel of 48 human kinases (selectivity score S(50%) of 0.04). Differences in compound binding mode and substituent preferences between the two VRKs were identified by the structure-activity relationship combined with the crystallographic analysis of key compounds. We expect our results to serve as a starting point for the design of more specific and potent inhibitors against each of the two VRKs.

  DOI：

  10.1021/acsmedchemlett.9b00082
• 作为产物：
  描述：

  2-甲基-3-氨基-5-溴吡啶 在 二碘甲烷 、 亚硝酸异戊酯 作用下， 以 乙腈 为溶剂， 以44 %的产率得到5-bromo-3-iodo-2-methylpyridine
  参考文献：
  名称：

  [EN] RIP1 KINASE INHIBITOR AND USE THEREOF
  [FR] INHIBITEUR DE LA KINASE RIP1 ET SON UTILISATION
  [ZH] RIP1激酶抑制剂及其用途

  摘要：

  提供通式(I)的抑制RIP1激酶的新颖化合物或其药学上可接受的盐，涉及包含此类化合物的组合物，以及此类化合物在抑制程序性坏死、抑制RIP1激酶或者治疗或预防至少部分地由RIP1激酶介导的疾病中的用途。

  公开号：

  WO2023039795A1

文献信息

• Development of Pyridine-based Inhibitors for the Human Vaccinia-related Kinases 1 and 2
  作者：Ricardo A. M. Serafim、Fernando H. de Souza Gama、Luiz A. Dutra、Caio V. dos Reis、Stanley N. S. Vasconcelos、André da Silva Santiago、Jéssica E. Takarada、Fúlvia Di Pillo、Hatylas Azevedo、Alessandra Mascarello、Jonathan M. Elkins、Katlin B. Massirer、Opher Gileadi、Cristiano R. W. Guimarães、Rafael M. Couñago

  DOI：10.1021/acsmedchemlett.9b00082

  日期：2019.9.12

  Vaccinia-related kinases 1 and 2 (VRK1 and VRK2) are human Ser/Thr protein kinases associated with increased cell division and neurological disorders. Nevertheless, the cellular functions of these proteins are not fully understood. Despite their therapeutic potential, there are no potent and specific inhibitors available for VRK1 or VRK2. We report here the discovery and elaboration of an aminopyridine scaffold as a basis for VRK1 and VRK2 inhibitors. The most potent compound for VRK1 (26) displayed an IC50 value of 150 nM and was fairly selective in a panel of 48 human kinases (selectivity score S(50%) of 0.04). Differences in compound binding mode and substituent preferences between the two VRKs were identified by the structure-activity relationship combined with the crystallographic analysis of key compounds. We expect our results to serve as a starting point for the design of more specific and potent inhibitors against each of the two VRKs.
• [EN] RIP1 KINASE INHIBITOR AND USE THEREOF<br/>[FR] INHIBITEUR DE LA KINASE RIP1 ET SON UTILISATION<br/>[ZH] RIP1激酶抑制剂及其用途
  申请人：[en]SIRONAX (BEIJING) CO., LTD.;[zh]维泰瑞隆（北京）生物科技有限公司

  公开号：WO2023039795A1

  公开（公告）日：2023-03-23

  提供通式(I)的抑制RIP1激酶的新颖化合物或其药学上可接受的盐，涉及包含此类化合物的组合物，以及此类化合物在抑制程序性坏死、抑制RIP1激酶或者治疗或预防至少部分地由RIP1激酶介导的疾病中的用途。