5-bromo-2-methoxypyridine-3-sulfonyl chloride | 1261584-19-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-bromo-2-methoxypyridine-3-sulfonyl chloride
• 英文别名: 5-Bromo-2-methoxypyridine-3-sulfonyl chloride
• CAS: 1261584-19-3
• 化学式: C₆H₅BrClNO₃S
• 分子量: 286.534
• InChiKey: HPGXYLFNEUZNHH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  64.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-bromo-2-methoxypyridine-3-sulfonyl chloride 在 tris-(dibenzylideneacetone)dipalladium(0) 、 caesium carbonate 、 2-二环己基磷-2',6'-二异丙氧基-1,1'-联苯 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 64.0h， 生成 methyl 4-(6-methoxy-5-(N-methylsulfamoyl)pyridin-3-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carboxylate
  参考文献：
  名称：

  Design and Development of a Macrocyclic Series Targeting Phosphoinositide 3-Kinase δ

  摘要：

  A macrocyclization approach has been explored on a series of benzoxazine phosphoinositide 3-kinase delta inhibitors, resulting in compounds with improved potency, permeability, and in vivo clearance while maintaining good solubility. The thermodynamics of binding was explored via surface plasmon resonance, and the binding of lead macrocycle 19 was found to be almost exclusively entropically driven compared with progenitor 18, which demonstrated both enthalpic and entropic contributions. The pharmacokinetics of macrocycle 19 was also explored in vivo, where it showed reduced clearance when compared with the progenitor 18. This work adds to the growing body of evidence that macrocyclization could provide an alternative and complementary approach to the design of small-molecule inhibitors, with the potential to deliver differentiated properties.

  DOI：

  10.1021/acsmedchemlett.0c00061
• 作为产物：
  描述：

  2-甲氧基-3,5-二溴吡啶 在 N-氯代丁二酰亚胺 、 水 、 sodium hydride 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 8.25h， 生成 5-bromo-2-methoxypyridine-3-sulfonyl chloride
  参考文献：
  名称：

  Design and Development of a Macrocyclic Series Targeting Phosphoinositide 3-Kinase δ

  摘要：

  A macrocyclization approach has been explored on a series of benzoxazine phosphoinositide 3-kinase delta inhibitors, resulting in compounds with improved potency, permeability, and in vivo clearance while maintaining good solubility. The thermodynamics of binding was explored via surface plasmon resonance, and the binding of lead macrocycle 19 was found to be almost exclusively entropically driven compared with progenitor 18, which demonstrated both enthalpic and entropic contributions. The pharmacokinetics of macrocycle 19 was also explored in vivo, where it showed reduced clearance when compared with the progenitor 18. This work adds to the growing body of evidence that macrocyclization could provide an alternative and complementary approach to the design of small-molecule inhibitors, with the potential to deliver differentiated properties.

  DOI：

  10.1021/acsmedchemlett.0c00061

文献信息

• KR20240069725A
  申请人：——

  公开号：——

  公开（公告）日：——
• Design and Development of a Macrocyclic Series Targeting Phosphoinositide 3-Kinase δ
  作者：Jonathan A. Spencer、Ian R. Baldwin、Nick Barton、Chun-Wa Chung、Máire A. Convery、Christopher D. Edwards、Craig Jamieson、David N. Mallett、James E. Rowedder、Paul Rowland、Daniel A. Thomas、Charlotte J. Hardy

  DOI：10.1021/acsmedchemlett.0c00061

  日期：2020.7.9

  A macrocyclization approach has been explored on a series of benzoxazine phosphoinositide 3-kinase delta inhibitors, resulting in compounds with improved potency, permeability, and in vivo clearance while maintaining good solubility. The thermodynamics of binding was explored via surface plasmon resonance, and the binding of lead macrocycle 19 was found to be almost exclusively entropically driven compared with progenitor 18, which demonstrated both enthalpic and entropic contributions. The pharmacokinetics of macrocycle 19 was also explored in vivo, where it showed reduced clearance when compared with the progenitor 18. This work adds to the growing body of evidence that macrocyclization could provide an alternative and complementary approach to the design of small-molecule inhibitors, with the potential to deliver differentiated properties.