N-甲基-N-(吡咯烷-3-基)乙酰胺盐酸盐 | 1624261-23-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 中文名称: N-甲基-N-(吡咯烷-3-基)乙酰胺盐酸盐
• 英文名称: Hydrochloric acid salt of N-Methyl-N-(S)-pyrrolidin-3-yl-acetamide
• 英文别名: N-Methyl-N-(pyrrolidin-3-yl)acetamide hydrochloride；N-methyl-N-pyrrolidin-3-ylacetamide;hydrochloride
• CAS: 1624261-23-9
• 化学式: C₇H₁₄N₂O*ClH
• 分子量: 178.662
• InChiKey: DZPRWZNOJJPSLX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.25
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  32.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-甲基-N-(吡咯烷-3-基)乙酰胺盐酸盐 在 potassium phosphate monohydrate 、 2-(dimethylaminomethyl)ferrocen-1-yl-palladium(II) chloride dinorbornylphosphine complex 、 sodium acetate 、 溶剂黄146 、 原甲酸三甲酯 作用下， 以 甲醇 、 乙醇 、 水 为溶剂， 反应 18.5h， 生成 N-(1-((2-(1H-indazol-4-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)pyrrolidin-3-yl)-N-methylacetamide
  参考文献：
  名称：

  Free–Wilson Analysis of Comprehensive Data on Phosphoinositide-3-kinase (PI3K) Inhibitors Reveals Importance of N-Methylation for PI3Kδ Activity

  摘要：

  Phosphoinositide-3-kinase delta (PI3K delta) is a critical regulator of cell growth and transformation and has been explored as a therapeutic target for a range of diseases. Through the exploration of the thienopyrimidine scaffold, we have identified a ligand-efficient methylation that leads to remarkable selectivity for PI3K delta over the closely related isoforms. Interrogation through the Free-Wilson analysis highlights the innate selectivity the thienopyrimidine scaffold has for PI3K delta and provides a predictive model for the activity against the PI3K isoforms.

  DOI：

  10.1021/acs.jmedchem.9b01499

文献信息

• EP4219479
  申请人：——

  公开号：——

  公开（公告）日：——
• Free–Wilson Analysis of Comprehensive Data on Phosphoinositide-3-kinase (PI3K) Inhibitors Reveals Importance of <i>N</i>-Methylation for PI3Kδ Activity
  作者：Lydia Barnes、Hollie Blaber、David T. K. Brooks、Lewis Byers、Daniel Buckley、Zoe C. Byron、Richard G. Chilvers、Liam Cochrane、Edward Cooney、Heather A. Damian、Luke Francis、Daniel Fu He、Jack M. J. Grace、Harley J. Green、Edmund J. P. Hogarth、Leyla Jusu、C. Elizabeth Killalea、Oliver King、Joseph Lambert、Zoe J. Lee、Nuria S. Lima、Christina L. Long、May-Li Mackinnon、Shusha Mahdy、Jolyon Matthews-Wright、Makenzie J. Millward、Matthew F. Meehan、Christopher Merrett、Lisa Morrison、Hal R. I. Parke、Charlotte Payne、Lawrence Payne、Craig Pike、Alexander Seal、Aaron J. Senior、Keenan M. Smith、Kamile Stanelyte、Joe Stillibrand、Rachel Szpara、Freya F. H. Taday、Antony M. Threadgould、Rohan J. Trainor、Jordan Waters、Oliver Williams、Carrie K. W. Wong、Katherine Wood、Nick Barton、Anna Gruszka、Zoe Henley、James E. Rowedder、Rosa Cookson、Katherine L. Jones、Alan Nadin、Ian E. Smith、Simon J. F. Macdonald、Andrew Nortcliffe

  DOI：10.1021/acs.jmedchem.9b01499

  日期：2019.11.27

  Phosphoinositide-3-kinase delta (PI3K delta) is a critical regulator of cell growth and transformation and has been explored as a therapeutic target for a range of diseases. Through the exploration of the thienopyrimidine scaffold, we have identified a ligand-efficient methylation that leads to remarkable selectivity for PI3K delta over the closely related isoforms. Interrogation through the Free-Wilson analysis highlights the innate selectivity the thienopyrimidine scaffold has for PI3K delta and provides a predictive model for the activity against the PI3K isoforms.