5-N-(tert-butyloxycarbonyl)aminoisophthalate-1,3-bis-O-(2,3,5,6-tetrafluorophenyl) ester | 380607-61-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 缩酚酸和缩酚酸环醚类
• 英文名称: 5-N-(tert-butyloxycarbonyl)aminoisophthalate-1,3-bis-O-(2,3,5,6-tetrafluorophenyl) ester
• 英文别名: Bis(2,3,5,6-tetrafluorophenyl) 5-[(2-methylpropan-2-yl)oxycarbonylamino]benzene-1,3-dicarboxylate
• CAS: 380607-61-4
• 化学式: C₂₅H₁₅F₈NO₆
• 分子量: 577.384
• InChiKey: RMQCWIYITMRBPH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  40
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  90.9
• 氢给体数：
  1
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  5-N-(tert-butyloxycarbonyl)aminoisophthalate-1,3-bis-O-(2,3,5,6-tetrafluorophenyl) ester 在 三乙胺 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 N-{3-[2-(2-{3-[3-Amino-5-(3-{2-[2-(3-tert-butoxycarbonylamino-propoxy)-ethoxy]-ethoxy}-propylcarbamoyl)-benzoylamino]-propoxy}-ethoxy)-ethoxy]-propyl}-2-[5-(2-oxo-hexahydro-thieno[3,4-d]imidazol-6-yl)-pentanoylamino]-succinamic acid
  参考文献：
  名称：

  Wilbur, D. S.; Chyan, M. K.; Hamlin, D. K., Journal of labelled compounds and radiopharmaceuticals, 2001, vol. 44, p. S741 - S743

  摘要：

  DOI：
• 作为产物：
  描述：

  5-氨基间苯二甲酸 在 sodium hydroxide 、 三乙胺 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.5h， 生成 5-N-(tert-butyloxycarbonyl)aminoisophthalate-1,3-bis-O-(2,3,5,6-tetrafluorophenyl) ester
  参考文献：
  名称：

  Wilbur, D. S.; Chyan, M. K.; Hamlin, D. K., Journal of labelled compounds and radiopharmaceuticals, 2001, vol. 44, p. S741 - S743

  摘要：

  DOI：

文献信息

• Design and Synthesis of Bis-Biotin-Containing Reagents for Applications Utilizing Monoclonal Antibody-Based Pretargeting Systems with Streptavidin Mutants
  作者：D. Scott Wilbur、Steven I. Park、Ming-Kuan Chyan、Feng Wan、Donald K. Hamlin、Jaideep Shenoi、Yukang Lin、Shani M. Wilbur、Franz Buchegger、Anastasia Pantelias、John M. Pagel、Oliver W. Press

  DOI：10.1021/bc100030q

  日期：2010.7.21

  Previous studies have shown that pretargeting protocols, using cancer-targeting fusion proteins, composed of 4 anti-CD20 single chain Fv (scFv) fragments and streptavidin (scFv(4)-SAv), followed by a biotinylated dendrimeric N-acetyl-galactosamine blood clearing agent (CA), 1, then a radiolabeled DOTA-biotin derivative (a monobiotin), 3a, can provide effective therapy for lymphoma xenografts in mouse models. A shortcoming in this pretargeting system is that endogenous biotin may affect its efficacy in patients. To circumvent this potential problem, we investigated a pretargeting system that employs anti-CD20 scFv(4)-SAv mutant fusion proteins with radioiodinated bis-biotin derivatives. With that combination of reagents, good localization of the radiolabel to lymphoma tumor xenografts was obtained in the presence of endogenous biotin. However, the blood clearance reagents employed in the studies were ineffective, resulting in abnormally high levels of radioactivity in other tissues. Thus, in the present investigation a bis-biotin-trigalactose blood clearance reagent, 2, was designed, synthesized, and evaluated in vivo. Additionally, another DOTA-biotin derivative (a bis-biotin), 4a, was designed and synthesized, such that radiometals (e.g., In-111, Y-90, Lu-177) could be used in the pretargeting protocols employing scFv(4)-SAv mutant fusion proteins. Studies in mice demonstrated that the CA 2 was more effective than CA 1 at removing [I-125]scFv(4)-SAv-S45A mutant fusion proteins from blood. Another in vivo study compared tumor targeting and normal tissue concentrations of the new reagents (2 and [In-111]4b) with standard reagents (1 and [In-111]3b) used in pretargeting protocols. The study showed that lymphoma xenografts could be targeted in the presence of endogenous biotin when anti-CD20 fusion potent containing SAv mutants (scFv(4)-SAv-S45A or scFv(4)-SAv-Y43A) were employed in combination with CA 2 and [In-111]4b). Importantly, normal tissue concentrations of [In-111]4b were similar to those obtained using the standard reagents (1 and [In-111]3b), except that the blood and liver concentrations were slightly higher with the new reagents. While the reasons for the higher blood and liver concentrations are unknown, the differences in the galactose structures of the clearance agents 1 and 2 may play a role.
• US8124364B2
  申请人：——

  公开号：US8124364B2

  公开（公告）日：2012-02-28
• Wilbur, D. S.; Chyan, M. K.; Hamlin, D. K., Journal of labelled compounds and radiopharmaceuticals, 2001, vol. 44, p. S741 - S743
  作者：Wilbur, D. S.、Chyan, M. K.、Hamlin, D. K.、Brechbiel, M.、Nilsson, R.、Sandberg, B. E. B.

  DOI：——

  日期：——