5-methanesulfonyl-7-(6-(morpholin-4-yl)-pyridin-3-yl)pyrido[2,3-d]pyrimidin-4-ylamine | 321522-71-8

• 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-methanesulfonyl-7-(6-(morpholin-4-yl)-pyridin-3-yl)pyrido[2,3-d]pyrimidin-4-ylamine
• 英文别名: 4-amino-5-sulfonylmethyl-7-(6-morpholinopyridin-3-yl)pyrido[2,3-d]pyridine；5-Methylsulfonyl-7-(6-morpholin-4-ylpyridin-3-yl)pyrido[2,3-d]pyrimidin-4-amine
• CAS: 321522-71-8
• 化学式: C₁₇H₁₈N₆O₃S
• 分子量: 386.434
• InChiKey: RBSIHVFADBZTQP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  133
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  邻氨基三氟甲苯 、 5-methanesulfonyl-7-(6-(morpholin-4-yl)-pyridin-3-yl)pyrido[2,3-d]pyrimidin-4-ylamine 在 potassium hydride 作用下， 以 四氢呋喃 为溶剂， 生成 7-(6-morpholin-4-ylpyridin-3-yl)-5-N-[2-(trifluoromethyl)phenyl]pyrido[2,3-d]pyrimidine-4,5-diamine
  参考文献：
  名称：

  Synthesis and structure-activity relationships of 5-heteroatom-substituted pyridopyrimidines as adenosine kinase inhibitors

  摘要：

  Under stressful conditions, many cells release adenosine to minimize tissue damage. Inhibition of intracellular adenosine kinase (AK) increases the local extracellular concentration of adenosine and its effect on traumatized tissue. The synthesis and SAR of a new series of pyridopyrimidines for the inhibition of AK are described. It was found that a range of analogs with position five substituted by an amine or ether functionality increased aqueous solubility while retaining the in vitro potency of initial leads. A narrower range of analogs was active in vivo in a rat inflammatory hyperalgesia model. (C) 2003 Editions scientifiques et medicales Elsevier SAS. All rights reserved.

  DOI：

  10.1016/s0223-5234(03)00019-9
• 作为产物：
  描述：

  2-氯-5-乙酰基吡啶 在 Oxone 、 ammonium sulfate 、 碳酸氢钠 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 二甲基亚砜 、 邻二氯苯 为溶剂， 反应 47.75h， 生成 5-methanesulfonyl-7-(6-(morpholin-4-yl)-pyridin-3-yl)pyrido[2,3-d]pyrimidin-4-ylamine
  参考文献：
  名称：

  Design of Adenosine Kinase Inhibitors from the NMR-Based Screening of Fragments

  摘要：

  A strategy is described for designing high-affinity ligands using information derived from the NMR-based screening of fragments. The method involves the fragmentation of an existing lead molecule, identification of suitable replacements for the fragments, and incorporation of the newly identified fragments into the original scaffold. Using this technique, novel substituents were rapidly identified and incorporated into lead inhibitors of adenosine kinase that exhibited potent in vitro and in vivo activities. This approach is a valuable strategy for modifying existing leads to improve their potency, bioavailability, or toxicity profile and thus represents a useful technique for lead optimization.

  DOI：

  10.1021/jm000373a

文献信息

• Synthesis and structure-activity relationships of 5-heteroatom-substituted pyridopyrimidines as adenosine kinase inhibitors
  作者：Gregory A Gfesser、Erol K Bayburt、Marlon Cowart、Stanley DiDomenico、Arthur Gomtsyan、Chih-Hung Lee、Andrew O Stewart、Michael F Jarvis、Elizabeth A Kowaluk、Shripad S Bhagwat

  DOI：10.1016/s0223-5234(03)00019-9

  日期：2003.3

  Under stressful conditions, many cells release adenosine to minimize tissue damage. Inhibition of intracellular adenosine kinase (AK) increases the local extracellular concentration of adenosine and its effect on traumatized tissue. The synthesis and SAR of a new series of pyridopyrimidines for the inhibition of AK are described. It was found that a range of analogs with position five substituted by an amine or ether functionality increased aqueous solubility while retaining the in vitro potency of initial leads. A narrower range of analogs was active in vivo in a rat inflammatory hyperalgesia model. (C) 2003 Editions scientifiques et medicales Elsevier SAS. All rights reserved.
• Design of Adenosine Kinase Inhibitors from the NMR-Based Screening of Fragments
  作者：Philip J. Hajduk、Arthur Gomtsyan、Stanley Didomenico、Marlon Cowart、Erol K. Bayburt、Larry Solomon、Jean Severin、Richard Smith、Karl Walter、Thomas F. Holzman、Andrew Stewart、Steve McGaraughty、Michael F. Jarvis、Elizabeth A. Kowaluk、Stephen W. Fesik

  DOI：10.1021/jm000373a

  日期：2000.12.1

  A strategy is described for designing high-affinity ligands using information derived from the NMR-based screening of fragments. The method involves the fragmentation of an existing lead molecule, identification of suitable replacements for the fragments, and incorporation of the newly identified fragments into the original scaffold. Using this technique, novel substituents were rapidly identified and incorporated into lead inhibitors of adenosine kinase that exhibited potent in vitro and in vivo activities. This approach is a valuable strategy for modifying existing leads to improve their potency, bioavailability, or toxicity profile and thus represents a useful technique for lead optimization.