N-(5-(3,4-dimethoxyphenyl)isothiazolo[5,4-b]pyridin-3-yl)cyclohexanecarboxamide

• 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: N-(5-(3,4-dimethoxyphenyl)isothiazolo[5,4-b]pyridin-3-yl)cyclohexanecarboxamide
• 英文别名: N-[5-(3,4-dimethoxyphenyl)-[1,2]thiazolo[5,4-b]pyridin-3-yl]cyclohexanecarboxamide
• 化学式: C₂₁H₂₃N₃O₃S
• 分子量: 397.498
• InChiKey: AYOYQYCMTQUYJP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-羟基-3-氰基吡啶 在 吡啶 、 ammonium hydroxide 、 sodium hypochlorite 、 四(三苯基膦)钯 、 五氯化磷 、 溴 、 sodium hydride 、 potassium carbonate 、 溶剂黄146 、 sodium hydroxide 、 三氯氧磷 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 62.0h， 生成 N-(5-(3,4-dimethoxyphenyl)isothiazolo[5,4-b]pyridin-3-yl)cyclohexanecarboxamide
  参考文献：
  名称：

  Discovery of Dual Death-Associated Protein Related Apoptosis Inducing Protein Kinase 1 and 2 Inhibitors by a Scaffold Hopping Approach

  摘要：

  DRAK2 emerged as a promising drug target for the treatment of autoimmune diseases and to prevent graft rejection after organ transplantation. Screening of a compound library in a DRAK2 binding assay led to the identification of an isothiazolo[5,4-b]pyridine derivative as a novel ligand for DRAK2, displaying a K-d value of 1.6 mu M. Subsequent medicinal chemistry work led to the discovery of a thieno[2,3-b]pyridine derivative with strong DRAK2 binding affinity (K-d = 9 nM). Moreover, this compound also behaves as a functional inhibitor of DRAK2 enzymatic activity, displaying an IC50 value of 0.82 mu M, although lacking selectivity, when tested against DRAK1. This paper describes for the first time functionally active dual DRAK1 and DRAK2 inhibitors that can be used as starting point for the synthesis of chemical tool compounds to study DRAK1 and DRAK2 biology, or they can be considered as hit compounds for hit-to-lead optimization campaigns in drug discovery programs.

  DOI：

  10.1021/jm5007929

文献信息

• Discovery of Dual Death-Associated Protein Related Apoptosis Inducing Protein Kinase 1 and 2 Inhibitors by a Scaffold Hopping Approach
  作者：Ling-Jie Gao、Sona Kovackova、Michal Šála、Anna Teresa Ramadori、Steven De Jonghe、Piet Herdewijn

  DOI：10.1021/jm5007929

  日期：2014.9.25

  DRAK2 emerged as a promising drug target for the treatment of autoimmune diseases and to prevent graft rejection after organ transplantation. Screening of a compound library in a DRAK2 binding assay led to the identification of an isothiazolo[5,4-b]pyridine derivative as a novel ligand for DRAK2, displaying a K-d value of 1.6 mu M. Subsequent medicinal chemistry work led to the discovery of a thieno[2,3-b]pyridine derivative with strong DRAK2 binding affinity (K-d = 9 nM). Moreover, this compound also behaves as a functional inhibitor of DRAK2 enzymatic activity, displaying an IC50 value of 0.82 mu M, although lacking selectivity, when tested against DRAK1. This paper describes for the first time functionally active dual DRAK1 and DRAK2 inhibitors that can be used as starting point for the synthesis of chemical tool compounds to study DRAK1 and DRAK2 biology, or they can be considered as hit compounds for hit-to-lead optimization campaigns in drug discovery programs.