(2S)-2-[2-[2-[2-[2-[2-[2-[[(1S)-1-carboxy-2-[[4-[2-(1,4,5,6-tetrahydropyrimidin-2-ylamino)ethoxy]benzoyl]amino]ethyl]sulfamoyl]ethylcarbamoyloxy]ethoxy]ethoxy]ethoxy]ethoxycarbonylamino]ethylsulfonylamino]-3-[[4-[2-(1,4,5,6-tetrahydropyrimidin-2-ylamino)ethoxy]benzoyl]amino]propanoic acid | 1257408-20-0

• 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: (2S)-2-[2-[2-[2-[2-[2-[2-[[(1S)-1-carboxy-2-[[4-[2-(1,4,5,6-tetrahydropyrimidin-2-ylamino)ethoxy]benzoyl]amino]ethyl]sulfamoyl]ethylcarbamoyloxy]ethoxy]ethoxy]ethoxy]ethoxycarbonylamino]ethylsulfonylamino]-3-[[4-[2-(1,4,5,6-tetrahydropyrimidin-2-ylamino)ethoxy]benzoyl]amino]propanoic acid
• CAS: 1257408-20-0
• 化学式: C₄₆H₇₀N₁₂O₁₉S₂
• 分子量: 1159.26
• InChiKey: DOULIFPELQSYIR-UWXQCODUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.1
• 重原子数：
  79
• 可旋转键数：
  42
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  438
• 氢给体数：
  12
• 氢受体数：
  23

反应信息

• 作为产物：
  描述：

  4-[2-(3,4,5,6-tetrahydropyrimidine-2-ylamino)ethyloxy]benzoyl-2-(S)-aminoethylsulfonyl-amino-β-alanine 、 2-(2-(2-(2-(1H-imidazole-1-carbonyloxy)ethoxy)ethoxy)ethoxy)ethyl 1H-imidazole-1-carboxylate 在 N,N-二异丙基乙胺 作用下， 以 二甲基亚砜 为溶剂， 反应 0.5h， 以68%的产率得到(2S)-2-[2-[2-[2-[2-[2-[2-[[(1S)-1-carboxy-2-[[4-[2-(1,4,5,6-tetrahydropyrimidin-2-ylamino)ethoxy]benzoyl]amino]ethyl]sulfamoyl]ethylcarbamoyloxy]ethoxy]ethoxy]ethoxy]ethoxycarbonylamino]ethylsulfonylamino]-3-[[4-[2-(1,4,5,6-tetrahydropyrimidin-2-ylamino)ethoxy]benzoyl]amino]propanoic acid
  参考文献：
  名称：

  Synthesis and evaluation of bivalent, peptidomimetic antagonists of the αvβ3 integrins

  摘要：

  Targeting the integrin alpha(v)beta(3) by directly interfering with its function is considered to be an effective and non-cytotoxic strategy for the treatment of tumor. In this study, a series of bivalent analogs of peptidomimetic integrin antagonists IA 1 and IAC 2 were designed, synthesized, and evaluated for their ability to inhibit the integrin alpha(v)beta(3). All the bivalent ligands exhibited increased potency compared to that of their monomeric counterparts for the integrin alpha(v)beta(3) with low nanomolar range binding affinity. The best bivalent ligand 6 tested in the series has an IC50 = 0.09 nM evaluated by ELISA assay. We conclude that multivalency is providing a useful template for the development novel integrin alpha(v)beta(3) antagonists as potential therapeutics. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.09.035

文献信息

• Synthesis and evaluation of bivalent, peptidomimetic antagonists of the αvβ3 integrins
  作者：Feng Li、Gouri S. Jas、Guoting Qin、King Li、Zheng Li

  DOI：10.1016/j.bmcl.2010.09.035

  日期：2010.11

  Targeting the integrin alpha(v)beta(3) by directly interfering with its function is considered to be an effective and non-cytotoxic strategy for the treatment of tumor. In this study, a series of bivalent analogs of peptidomimetic integrin antagonists IA 1 and IAC 2 were designed, synthesized, and evaluated for their ability to inhibit the integrin alpha(v)beta(3). All the bivalent ligands exhibited increased potency compared to that of their monomeric counterparts for the integrin alpha(v)beta(3) with low nanomolar range binding affinity. The best bivalent ligand 6 tested in the series has an IC50 = 0.09 nM evaluated by ELISA assay. We conclude that multivalency is providing a useful template for the development novel integrin alpha(v)beta(3) antagonists as potential therapeutics. (C) 2010 Elsevier Ltd. All rights reserved.