Tert-butyl 2-[4-[2-amino-3-[[1-[(4-methoxyphenyl)methyl]-4-methyl-2-oxopyridin-3-yl]amino]-3-oxopropyl]phenyl]-2-methylpropanoate | 356578-41-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: Tert-butyl 2-[4-[2-amino-3-[[1-[(4-methoxyphenyl)methyl]-4-methyl-2-oxopyridin-3-yl]amino]-3-oxopropyl]phenyl]-2-methylpropanoate
• CAS: 356578-41-1
• 化学式: C₃₁H₃₉N₃O₅
• 分子量: 533.668
• InChiKey: UIKFORHEPOYEIO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  39
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  111
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Tert-butyl 2-[4-[2-amino-3-[[1-[(4-methoxyphenyl)methyl]-4-methyl-2-oxopyridin-3-yl]amino]-3-oxopropyl]phenyl]-2-methylpropanoate 在 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 2-{4-[2-[1-(4-Methoxy-benzyl)-4-methyl-2-oxo-1,2-dihydro-pyridin-3-ylcarbamoyl]-2-(2-naphthalen-2-yl-acetylamino)-ethyl]-phenyl}-2-methyl-propionic acid
  参考文献：
  名称：

  Nonpeptidic, Monocharged, Cell Permeable Ligands for the p56lck SH2 Domain

  摘要：

  p561ck is a member of the src family of tyrosine kinases and plays a critical role in the signal transduction events that lead to T cell activation. Ligands for the p561ck SH2 domain have the potential to disrupt the interaction of p561ck with its substrates and derail the signaling cascade that leads to the production of cytokines such as interleukin-2. Starting from the quintuply charged (at physiological pH) phosphorylated tetrapeptide, AcpYEEI, we recently disclosed (J. Med. Chem. 1999, 42, 722 and J. Med. Chem. 1999, 42, 1757) the design of the modified dipeptide 3, which carries just two charges at physiological pH. Here we present the elaboration of 3 to the nonpeptidic, monocharged compound, 9S. This molecule displays good binding affinity for the p561ck SH2 domain (K-d 1 muM) and good cell permeation, and this combination of properties allowed us to demonstrate clear-cut inhibitory effects on a very early event in T cell activation, namely calcium mobilization.

  DOI：

  10.1021/jm000446q
• 作为产物：
  描述：

  4-iodo-(1'-carboxy-1'-methyl)ethylbenzene 在 10percent Pd/C 盐酸 、 palladium diacetate 、 草酰氯 、 四丁基氯化铵 、 氢气 、 碳酸氢钠 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 80.0 ℃ 、310.27 kPa 条件下， 反应 84.92h， 生成 Tert-butyl 2-[4-[2-amino-3-[[1-[(4-methoxyphenyl)methyl]-4-methyl-2-oxopyridin-3-yl]amino]-3-oxopropyl]phenyl]-2-methylpropanoate
  参考文献：
  名称：

  Nonpeptidic, Monocharged, Cell Permeable Ligands for the p56lck SH2 Domain

  摘要：

  p561ck is a member of the src family of tyrosine kinases and plays a critical role in the signal transduction events that lead to T cell activation. Ligands for the p561ck SH2 domain have the potential to disrupt the interaction of p561ck with its substrates and derail the signaling cascade that leads to the production of cytokines such as interleukin-2. Starting from the quintuply charged (at physiological pH) phosphorylated tetrapeptide, AcpYEEI, we recently disclosed (J. Med. Chem. 1999, 42, 722 and J. Med. Chem. 1999, 42, 1757) the design of the modified dipeptide 3, which carries just two charges at physiological pH. Here we present the elaboration of 3 to the nonpeptidic, monocharged compound, 9S. This molecule displays good binding affinity for the p561ck SH2 domain (K-d 1 muM) and good cell permeation, and this combination of properties allowed us to demonstrate clear-cut inhibitory effects on a very early event in T cell activation, namely calcium mobilization.

  DOI：

  10.1021/jm000446q

文献信息

• Nonpeptidic, Monocharged, Cell Permeable Ligands for the p56lck SH2 Domain
  作者：John R. Proudfoot、Rajashehar Betageri、Mario Cardozo、Thomas A. Gilmore、Susan Glynn、Eugene R. Hickey、Scott Jakes、Alisa Kabcenell、Thomas M. Kirrane、Annette K. Tibolla、Susan Lukas、Usha R. Patel、Rajiv Sharma、Mehran Yazdanian、Neil Moss、Pierre L. Beaulieu、Dale R. Cameron、Jean-Marie Ferland、Jean Gauthier、James Gillard、Vida Gorys、Martin Poirier、Jean Rancourt、Dominik Wernic、Montse Llinas-Brunet

  DOI：10.1021/jm000446q

  日期：2001.7.1

  p561ck is a member of the src family of tyrosine kinases and plays a critical role in the signal transduction events that lead to T cell activation. Ligands for the p561ck SH2 domain have the potential to disrupt the interaction of p561ck with its substrates and derail the signaling cascade that leads to the production of cytokines such as interleukin-2. Starting from the quintuply charged (at physiological pH) phosphorylated tetrapeptide, AcpYEEI, we recently disclosed (J. Med. Chem. 1999, 42, 722 and J. Med. Chem. 1999, 42, 1757) the design of the modified dipeptide 3, which carries just two charges at physiological pH. Here we present the elaboration of 3 to the nonpeptidic, monocharged compound, 9S. This molecule displays good binding affinity for the p561ck SH2 domain (K-d 1 muM) and good cell permeation, and this combination of properties allowed us to demonstrate clear-cut inhibitory effects on a very early event in T cell activation, namely calcium mobilization.