4-(2-amino-5-bromopyridin-3-yl)benzamide | 1216771-56-0

• 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: 4-(2-amino-5-bromopyridin-3-yl)benzamide
• CAS: 1216771-56-0
• 化学式: C₁₂H₁₀BrN₃O
• 分子量: 292.135
• InChiKey: PLOCUEUKFCAPEX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  82
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(2-amino-5-bromopyridin-3-yl)benzamide 、 2-(2,3-二氢噻吩并[3,4-b][1,4]二噁英-5-基)-4,4,5,5-四甲基-1,3,2-二噁硼烷 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 反应 0.67h， 以58%的产率得到4-(2-amino-5-(2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)pyridin-3-yl)benzamide
  参考文献：
  名称：

  Identification and characterisation of 2-aminopyridine inhibitors of checkpoint kinase 2

  摘要：

  5-(Hetero)aryl-3-(4-carboxamidophenyl)-2-aminopyridine inhibitors of CHK2 were identified from high throughput screening of a kinase-focussed compound library. Rapid exploration of the hits through straightforward chemistry established structure-activity relationships and a proposed ATP-competitive binding mode which was verified by X-ray crystallography of several analogues bound to CHK2. Variation of the 5-(hetero)aryl substituent identified bicyclic dioxolane and dioxane groups which improved the affinity and the selectivity of the compounds for CHK2 versus CHK1. The 3-(4-carboxamidophenyl) substituent could be successfully replaced by acyclic omega-aminoalkylamides, which made additional polar interactions within the binding site and led to more potent inhibitors of CHK2. Compounds from this series showed activity in cell-based mechanistic assays for inhibition of CHK2.

  DOI：

  10.1016/j.bmc.2009.11.058
• 作为产物：
  描述：

  4-(2-aminopyridin-3-yl)benzamide 在 1,3-二溴-5,5-二甲基海因 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以61%的产率得到4-(2-amino-5-bromopyridin-3-yl)benzamide
  参考文献：
  名称：

  Identification and characterisation of 2-aminopyridine inhibitors of checkpoint kinase 2

  摘要：

  5-(Hetero)aryl-3-(4-carboxamidophenyl)-2-aminopyridine inhibitors of CHK2 were identified from high throughput screening of a kinase-focussed compound library. Rapid exploration of the hits through straightforward chemistry established structure-activity relationships and a proposed ATP-competitive binding mode which was verified by X-ray crystallography of several analogues bound to CHK2. Variation of the 5-(hetero)aryl substituent identified bicyclic dioxolane and dioxane groups which improved the affinity and the selectivity of the compounds for CHK2 versus CHK1. The 3-(4-carboxamidophenyl) substituent could be successfully replaced by acyclic omega-aminoalkylamides, which made additional polar interactions within the binding site and led to more potent inhibitors of CHK2. Compounds from this series showed activity in cell-based mechanistic assays for inhibition of CHK2.

  DOI：

  10.1016/j.bmc.2009.11.058

文献信息

• [EN] STK4 INHIBITORS FOR TREATMENT OF HEMATOLOGIC MALIGNANCIES<br/>[FR] INHIBITEURS STK4 POUR LE TRAITEMENT DE MALIGNITÉS HÉMATOLOGIQUES
  申请人：DANA FARBER CANCER INST INC

  公开号：WO2016161145A1

  公开（公告）日：2016-10-06

  The application relates to compounds of Formula (I'): which modulate the activity of a kinase (e.g., STK4), a pharmaceutical composition comprising the compound, and a method of treating or preventing a disease or disorder associated with the modulation of a kinase, such as STK4.

  该申请涉及公式（I'）的化合物，该化合物调节激酶（例如STK4）的活性，包括该化合物的药物组合物，以及治疗或预防与激酶调节相关的疾病或紊乱的方法，如STK4。
• NEW ANTI-MALARIAL AGENTS
  申请人：Witty Michael John

  公开号：US20120295905A1

  公开（公告）日：2012-11-22

  The present invention is related to a use of aminopyridine derivatives in the manufacture of a medicament for preventing or treating malaria. Specifically, the present invention is related to aminopyridine derivatives useful for the preparation of a pharmaceutical formulation for the inhibition of malaria parasite proliferation.

  本发明涉及氨基吡啶衍生物在制造预防或治疗疟疾药物方面的用途。具体而言，本发明涉及氨基吡啶衍生物，可用于制备制药配方，以抑制疟原虫的增殖。
• STK4 inhibitors for treatment of hematologic malignancies
  申请人：Dana-Farber Cancer Institute, Inc.

  公开号：US10710978B2

  公开（公告）日：2020-07-14

  The application relates to compounds of Formula (I′): which modulate the activity of a kinase (e.g., STK4), a pharmaceutical composition comprising the compound, and a method of treating or preventing a disease or disorder associated with the modulation of a kinase, such as STK4.

  本申请涉及式（I′）化合物： 调节激酶（如 STK4）活性的化合物，包含该化合物的药物组合物，以及治疗或预防与激酶（如 STK4）调节有关的疾病或紊乱的方法。
• 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.
• STK4 INHIBITORS FOR TREATMENT OF HEMATOLOGIC MALIGNANCIES
  申请人：Dana-Farber Cancer Institute, Inc.

  公开号：US20180111916A1

  公开（公告）日：2018-04-26

  The application relates to compounds of Formula (I′): which modulate the activity of a kinase (e.g., STK4), a pharmaceutical composition comprising the compound, and a method of treating or preventing a disease or disorder associated with the modulation of a kinase, such as STK4.