| 1407150-82-6

• 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
• CAS: 1407150-82-6
• 化学式: C₄₂H₆₇F₂N₅O₁₄
• 分子量: 904.016
• InChiKey: LFYSICZRJWBRFX-SZJWEORGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.17
• 重原子数：
  63.0
• 可旋转键数：
  13.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  226.41
• 氢给体数：
  4.0
• 氢受体数：
  18.0

反应信息

• 作为反应物：
  描述：

  在 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 8.0h， 以0.37 g的产率得到1-O-(2-difluoromethyl-4-(1-(4,7,10-triscarboxymethyl-(1,4,7,10-tetraazacyclododecyl))acetamido)phenyl)-β-D-glucopyranuronate
  参考文献：
  名称：

  Development of a Gd(III)-Based Receptor-Induced Magnetization Enhancement (RIME) Contrast Agent for β-Glucuronidase Activity Profiling

  摘要：

  beta-Glucuronidase is a key lysosomal enzyme and is often overexpressed in necrotic tumor masses. We report here the synthesis of a pro receptor induced magnetization enhancement (pro RIME) magnetic resonance imaging (MRI) contrast agent ([Gd(DOTA-FP beta Gu)]) for molecular imaging of beta-glucuronidase activity in tumor tissues. The contrast agent consists of two parts, a gadolinium complex and a beta-glucuronidase substrate (beta-D-glucopyranuronic acid). The binding association constant (K-A) of [Gd(DOTA-FP beta Gu)] is 7.42 X 10(2), which is significantly lower than that of a commercially available MS-325 (K-A = 3.0 x 10(4)) RIME contrast agent. The low K-A value of [Gd(DOTA-FP beta Gu)] is due to the pendant beta-D-glucopyranuronic acid moiety. Therefore, [Gd(DOTA-FP beta Gu)] can be used for detection of beta-glucuronidase through RIME modulation. The detail mechanism of enzymatic activation of [Gd(DOTA-FP beta Gu)] was elucidated by LC-MS. The kinetics of beta-glucuronidase catalyzed hydrolysis of [Eu(DOTA-FP beta Gu)] at pH 7.4 best fit the Miechalis-Menten kinetic mode with K-m = 1.38 mM, K-cat = 3.76 x 10(3), and k(cat)/K-m = 2.72 x 10(3) M-1 s(-1). The low K-m value indicates high affinity of beta-glucuronidase for [Gd(DOTA-FP beta Gu)] FP beta Gu) at physiological pH. Relaxometric studies revealed that T-1 relaxivity of [Gd(DOTA-FP beta Gu)] changes in response to the concentration of beta-glucuronidase. Consistent with the relaxometric studies, [Gd(DOTA-FP beta Gu)] showed significant change in MR image signal in the presence of beta-glucuronidase and HSA. In vitro and in vivo MR images demonstrated appreciable differences in signal enhancement in the cell lines and tumor xenografts in accordance to their expression levels of beta-glucuronidase.[GRAPHICS].

  DOI：

  10.1021/ic301827p
• 作为产物：
  描述：

  methyl 1-O-(2-difluoromethyl-4-nitrophenyl)-2,3,4-tri-O-acetyl-β-D-glucopyranuronate 在 甲醇 、 palladium 10% on activated carbon 、 氢气 、 sodium methylate 、 potassium carbonate 、 三乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 20.0~70.0 ℃ 、182.4 kPa 条件下， 反应 26.0h， 生成
  参考文献：
  名称：

  Development of a Gd(III)-Based Receptor-Induced Magnetization Enhancement (RIME) Contrast Agent for β-Glucuronidase Activity Profiling

  摘要：

  beta-Glucuronidase is a key lysosomal enzyme and is often overexpressed in necrotic tumor masses. We report here the synthesis of a pro receptor induced magnetization enhancement (pro RIME) magnetic resonance imaging (MRI) contrast agent ([Gd(DOTA-FP beta Gu)]) for molecular imaging of beta-glucuronidase activity in tumor tissues. The contrast agent consists of two parts, a gadolinium complex and a beta-glucuronidase substrate (beta-D-glucopyranuronic acid). The binding association constant (K-A) of [Gd(DOTA-FP beta Gu)] is 7.42 X 10(2), which is significantly lower than that of a commercially available MS-325 (K-A = 3.0 x 10(4)) RIME contrast agent. The low K-A value of [Gd(DOTA-FP beta Gu)] is due to the pendant beta-D-glucopyranuronic acid moiety. Therefore, [Gd(DOTA-FP beta Gu)] can be used for detection of beta-glucuronidase through RIME modulation. The detail mechanism of enzymatic activation of [Gd(DOTA-FP beta Gu)] was elucidated by LC-MS. The kinetics of beta-glucuronidase catalyzed hydrolysis of [Eu(DOTA-FP beta Gu)] at pH 7.4 best fit the Miechalis-Menten kinetic mode with K-m = 1.38 mM, K-cat = 3.76 x 10(3), and k(cat)/K-m = 2.72 x 10(3) M-1 s(-1). The low K-m value indicates high affinity of beta-glucuronidase for [Gd(DOTA-FP beta Gu)] FP beta Gu) at physiological pH. Relaxometric studies revealed that T-1 relaxivity of [Gd(DOTA-FP beta Gu)] changes in response to the concentration of beta-glucuronidase. Consistent with the relaxometric studies, [Gd(DOTA-FP beta Gu)] showed significant change in MR image signal in the presence of beta-glucuronidase and HSA. In vitro and in vivo MR images demonstrated appreciable differences in signal enhancement in the cell lines and tumor xenografts in accordance to their expression levels of beta-glucuronidase.[GRAPHICS].

  DOI：

  10.1021/ic301827p