dibenzyl 3,3'-(2-(tert-butoxycarbonylamino)ethylazanediyl)dipropanoate | 1206475-64-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: dibenzyl 3,3'-(2-(tert-butoxycarbonylamino)ethylazanediyl)dipropanoate
• 英文别名: benzyl 3,3'-(2-(tert-butoxycarbonylamino)ethylazanediyl)dipropanoate；Benzyl 3-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethyl-(3-oxo-3-phenylmethoxypropyl)amino]propanoate
• CAS: 1206475-64-0
• 化学式: C₂₇H₃₆N₂O₆
• 分子量: 484.593
• InChiKey: ZEESPCLGNNGAOC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  35
• 可旋转键数：
  17
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  94.2
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  dibenzyl 3,3'-(2-(tert-butoxycarbonylamino)ethylazanediyl)dipropanoate 在 palladium-carbon 氢气 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 以74%的产率得到3,3'-((2-((tert-butoxycarbonyl)amino)ethyl)azanediyl)dipropanoic acid
  参考文献：
  名称：

  RADIOLABELED BBN-RGD HETERODIMERS FOR CANCER TARGETING

  摘要：

  本公开涵盖了用于将放射性标记和其他配体传递到细胞或组织的异源二聚体组合物，特别是用于定位和成像表达整合素和胃泌素释放肽受体的细胞和组织的组合物及其使用方法。因此，首先涵盖了可以包括异源二聚体探针的组合物，该异源二聚体探针包括第一肽结构域，其中包括能够选择性结合整合素的结构域；第二肽结构域，其中包括能够选择性结合胃泌素释放肽受体的结构域；连接第一肽结构域和第二肽结构域的连接物；以及一个假体基团。第一肽结构域包括至少一个三肽，其氨基酸序列为精氨酸-甘氨酸-天冬氨酸，第二结构域可以是肽骨胃素(7-14)。假体基团可以是氟同位素18F，以便通过正电子发射断层扫描或单光子发射计算机断层扫描，或金属放射性同位素来检测异源二聚体探针。放射性同位素可以通过螯合连接物连接到探针上。

  公开号：

  US20100015058A1
• 作为产物：
  描述：

  N-叔丁氧羰基-1,2-乙二胺 、 丙烯酸苄酯 反应 168.0h， 以89%的产率得到dibenzyl 3,3'-(2-(tert-butoxycarbonylamino)ethylazanediyl)dipropanoate
  参考文献：
  名称：

  A new 18F-labeled BBN-RGD peptide heterodimer with a symmetric linker for prostate cancer imaging

  摘要：

  A peptide heterodimer comprises two different receptor-targeting peptide ligands. Molecular imaging probes based on dual-receptor targeting peptide heterodimers exhibit improved tumor targeting efficacy for multi-receptor expressing tumors compared with their parent single-receptor targeting peptide monomers. Previously we have developed bombesin (BBN)-RGD (Arg-Gly-Asp) peptide heterodimers, in which BBN and RGD are covalently connected with an asymmetric glutamate linker (J Med Chem 52:425-432, 2009). Although F-18-labeled heterodimers showed significantly better microPET imaging quality than F-18-labeled RGD and BBN monomers in a PC-3 xenograft model which co-expresses gastrin-releasing peptide receptor (GRPR) and integrin alpha v beta 3, tedious heterodimer synthesis due to the asymmetric nature of glutamate linker restricts their clinical applications. In this study, we report the use of a symmetric linker AEADP [AEADP = 3,3'-(2-aminoethylazanediyl)dipropanoic acid] for the synthesis of BBN-RGD peptide heterodimer. The F-18-labeled heterodimer (F-18-FB-AEADP-BBN-RGD) showed comparable microPET imaging results with glutamate linked BBN-RGD heterodimers, indicating that the replacement of glutamate linker with AEADP linker did not affect the biological activities of BBN-RGD heterodimer. The heterodimer synthesis is rather easy and straightforward. Because tumors often co-express multiple receptors, the use of a symmetric linker provides a general method of fast assembly of various peptide heterodimers for imaging multi-receptor expressing tumors.

  DOI：

  10.1007/s00726-010-0762-5

文献信息

• RADIOLABELED BBN-RGD HETERODIMERS FOR CANCER TARGETING
  申请人：LI ZIBO

  公开号：US20100015058A1

  公开（公告）日：2010-01-21

  The present disclosure encompasses heterodimeric compositions for delivering radiolabeled and other ligands to a cell or tissue, and particularly to compositions and methods of use thereof for targeting and imaging cells and tissues expressing both an integrin and gastrin-releasing peptide receptor, in particular prostate cancer cells. The disclosure, therefore, firstly encompasses compositions that can comprise a heterodimeric probe comprising a first peptide domain comprising a moiety capable of selectively binding to an integrin; a second peptide domain comprising a moiety capable of selectively binding to a gastrin-releasing peptide receptor; a linker connecting the first peptide domain and the second peptide domain; and a prosthetic group. The first peptide domain comprises at least one tripeptide comprising the amino acid sequence of arginine-glycine-aspartate, and the second domain can be the peptide bombesin(7-14). The prosthetic group can be the fluoride isotope 18 F so that the heterodimeric probe may be detected by positron emission tomography or by single photon emission computed tomography, or a metal radionuclide. The radionuclide may be attached to the probe via a chelating tether.

  本公开涵盖了用于将放射性标记和其他配体传递到细胞或组织的异源二聚体组合物，特别是用于定位和成像表达整合素和胃泌素释放肽受体的细胞和组织的组合物及其使用方法。因此，首先涵盖了可以包括异源二聚体探针的组合物，该异源二聚体探针包括第一肽结构域，其中包括能够选择性结合整合素的结构域；第二肽结构域，其中包括能够选择性结合胃泌素释放肽受体的结构域；连接第一肽结构域和第二肽结构域的连接物；以及一个假体基团。第一肽结构域包括至少一个三肽，其氨基酸序列为精氨酸-甘氨酸-天冬氨酸，第二结构域可以是肽骨胃素(7-14)。假体基团可以是氟同位素18F，以便通过正电子发射断层扫描或单光子发射计算机断层扫描，或金属放射性同位素来检测异源二聚体探针。放射性同位素可以通过螯合连接物连接到探针上。
• A new 18F-labeled BBN-RGD peptide heterodimer with a symmetric linker for prostate cancer imaging
  作者：Yongjun Yan、Kai Chen、Min Yang、Xilin Sun、Shuanglong Liu、Xiaoyuan Chen

  DOI：10.1007/s00726-010-0762-5

  日期：2011.7

  A peptide heterodimer comprises two different receptor-targeting peptide ligands. Molecular imaging probes based on dual-receptor targeting peptide heterodimers exhibit improved tumor targeting efficacy for multi-receptor expressing tumors compared with their parent single-receptor targeting peptide monomers. Previously we have developed bombesin (BBN)-RGD (Arg-Gly-Asp) peptide heterodimers, in which BBN and RGD are covalently connected with an asymmetric glutamate linker (J Med Chem 52:425-432, 2009). Although F-18-labeled heterodimers showed significantly better microPET imaging quality than F-18-labeled RGD and BBN monomers in a PC-3 xenograft model which co-expresses gastrin-releasing peptide receptor (GRPR) and integrin alpha v beta 3, tedious heterodimer synthesis due to the asymmetric nature of glutamate linker restricts their clinical applications. In this study, we report the use of a symmetric linker AEADP [AEADP = 3,3'-(2-aminoethylazanediyl)dipropanoic acid] for the synthesis of BBN-RGD peptide heterodimer. The F-18-labeled heterodimer (F-18-FB-AEADP-BBN-RGD) showed comparable microPET imaging results with glutamate linked BBN-RGD heterodimers, indicating that the replacement of glutamate linker with AEADP linker did not affect the biological activities of BBN-RGD heterodimer. The heterodimer synthesis is rather easy and straightforward. Because tumors often co-express multiple receptors, the use of a symmetric linker provides a general method of fast assembly of various peptide heterodimers for imaging multi-receptor expressing tumors.