2-((4-((3,4-dichlorophenethyl)amino)-6-(pyrrolidin-1-yl)-1,3,5-triazin-2-yl)amino)-N-ethyl-2,3-dihydro-1H-indene-2-carboxamide | 1590462-56-8

• 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: 2-((4-((3,4-dichlorophenethyl)amino)-6-(pyrrolidin-1-yl)-1,3,5-triazin-2-yl)amino)-N-ethyl-2,3-dihydro-1H-indene-2-carboxamide
• 英文别名: 2-[[4-[2-(3,4-dichlorophenyl)ethylamino]-6-pyrrolidin-1-yl-1,3,5-triazin-2-yl]amino]-N-ethyl-1,3-dihydroindene-2-carboxamide
• CAS: 1590462-56-8
• 化学式: C₂₇H₃₁Cl₂N₇O
• 分子量: 540.495
• InChiKey: JQMVIRYMEBHHLH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  95.1
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  N-叔丁氧羰基-2-氨基茚满-2-羧酸 在 N,N-二异丙基乙胺 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N-甲基吡咯烷酮 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 2.25h， 生成 2-((4-((3,4-dichlorophenethyl)amino)-6-(pyrrolidin-1-yl)-1,3,5-triazin-2-yl)amino)-N-ethyl-2,3-dihydro-1H-indene-2-carboxamide
  参考文献：
  名称：

  Application of encoded library technology (ELT) to a protein–protein interaction target: Discovery of a potent class of integrin lymphocyte function-associated antigen 1 (LFA-1) antagonists

  摘要：

  The inhibition of protein-protein interactions remains a challenge for traditional small molecule drug discovery. Here we describe the use of DNA-encoded library technology for the discovery of small molecules that are potent inhibitors of the interaction between lymphocyte function-associated antigen 1 and its ligand intercellular adhesion molecule 1. A DNA-encoded library with a potential complexity of 4.1 billion compounds was exposed to the I-domain of the target protein and the bound ligands were affinity selected, yielding an enriched small-molecule hit family. Compounds representing this family were synthesized without their DNA encoding moiety and found to inhibit the lymphocyte function-associated antigen 1/intercellular adhesion molecule-1 interaction with submicromolar potency in both ELISA and cell adhesion assays. Re-synthesized compounds conjugated to DNA or a fluorophore were demonstrated to bind to cells expressing the target protein. (c) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.01.050

文献信息

• Application of encoded library technology (ELT) to a protein–protein interaction target: Discovery of a potent class of integrin lymphocyte function-associated antigen 1 (LFA-1) antagonists
  作者：Christopher S. Kollmann、Xiaopeng Bai、Ching-Hsuan Tsai、Hongfang Yang、Kenneth E. Lind、Steven R. Skinner、Zhengrong Zhu、David I. Israel、John W. Cuozzo、Barry A. Morgan、Koichi Yuki、Can Xie、Timothy A. Springer、Motomu Shimaoka、Ghotas Evindar

  DOI：10.1016/j.bmc.2014.01.050

  日期：2014.4

  The inhibition of protein-protein interactions remains a challenge for traditional small molecule drug discovery. Here we describe the use of DNA-encoded library technology for the discovery of small molecules that are potent inhibitors of the interaction between lymphocyte function-associated antigen 1 and its ligand intercellular adhesion molecule 1. A DNA-encoded library with a potential complexity of 4.1 billion compounds was exposed to the I-domain of the target protein and the bound ligands were affinity selected, yielding an enriched small-molecule hit family. Compounds representing this family were synthesized without their DNA encoding moiety and found to inhibit the lymphocyte function-associated antigen 1/intercellular adhesion molecule-1 interaction with submicromolar potency in both ELISA and cell adhesion assays. Re-synthesized compounds conjugated to DNA or a fluorophore were demonstrated to bind to cells expressing the target protein. (c) 2014 Elsevier Ltd. All rights reserved.