1-methyl 2-(benzoylthio)butanedioic acid monoester | 146725-66-8

• 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: 1-methyl 2-(benzoylthio)butanedioic acid monoester
• 英文别名: 3-Benzoylsulfanyl-4-methoxy-4-oxobutanoic acid
• CAS: 146725-66-8
• 化学式: C₁₂H₁₂O₅S
• 分子量: 268.29
• InChiKey: SLOYKONOXFTPAA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  106
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-methyl 2-(benzoylthio)butanedioic acid monoester 在 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 反应 20.5h， 生成 dimethyl 2,11-bis(benzoylthio)-4,9-dioxo-5,8-diazadodecanodioate
  参考文献：
  名称：

  Dicarboxylate diamide dimercaptide (N2S2) technetium-99m complexes: synthesis and biological evaluation as potential renal radiopharmaceuticals

  摘要：

  Novel diamide dimercaptide (N2S2) ligands 4, 5, and 8 have been synthesized and evaluated as potential renal radiopharmaceuticals. The target compounds were prepared in modest overall yields of 22 %, 19 %, and 20 %, respectively, using readily available starting materials. Following in situ deprotection, Tc-99m complexes of high radiochemical purity were obtained in excellent yield and were found to be stable for up to 6 h. The Tc-99 complex of ligand 8 was isolated as the AsPh4 salt. The X-ray crystallographic data for ([TcO(8)]AsPh4)-Tc-99 (space group P2(1)/n: Z = 4, a = 9.342(3) angstrom; b = 18.594(5) angstrom; c = 18.417(7) angstrom; beta, deg = 90.61(3); V, angstrom3 = 3199.1(20)) show that the Tc is bound to both thiolate sulfur atoms and to two deprotonated amide nitrogen atoms. The coordination geometry about the Tc is square-pyramidal with an -yl oxygen atom in the apical position. The Tc-N bond distances (2.002(12) and 1.984(12) angstrom), the Tc-S bond distances (2.300(5) and 2.286(5) angstrom), and the Tc-O bond distance (1.667(11) angstrom) are in good agreement with bond lengths reported for similar complexes. The carboxylate groups are not bonded to the Tc atom in the solid state, nor in CDCl3 solution, as evidenced by X-ray crystal data and solution NMR data, respectively. In the solid state, ([TcO(8)]AsPh4)-Tc-99 is monoanionic, therefore, at physiological pH, ([TcO(8)])-Tc-99m is presumably trianionic. Biodistribution studies performed in rats with the Tc-99m complexes revealed slow blood clearance and high muscle uptake for these agents. Modest hepatobiliary excretion was observed, and low quantities of the complexes were found in the heart, lungs, and spleen after 1 h. The urinary excretion of the Tc-99m complexes of ligands 4, 5, and 8 was found to be slow when compared to the excretion of [I-131]OIH in rats (22%, 22%, and 32% vs 85-86%, respectively). Protein binding of Tc-99m complexes of ligands 4,5, and 8 in both rat and monkey plasma was found to be similar to MAG3. While the synthetic schemes reported here supply facile routes to novel N2S2 ligands, biodistribution studies of the Tc-99m complexes performed on rats revealed slow renal excretion rates, accompanied by slow blood clearance and high uptake in muscle tissue. Preliminary planar imaging studies in monkeys also revealed slow renal excretion for these agents. The Tc-99m complexes evaluated here are poor candidates as renal radiopharmaceuticals.

  DOI：

  10.1021/jm00060a011
• 作为产物：
  描述：

  硫代苯甲酸 、 alkaline earth salt of/the/ methylsulfuric acid 在 过氧化苯甲酰 作用下， 以 甲醇 、 乙醚 为溶剂， 反应 7.0h， 生成 1-methyl 2-(benzoylthio)butanedioic acid monoester
  参考文献：
  名称：

  Dicarboxylate diamide dimercaptide (N2S2) technetium-99m complexes: synthesis and biological evaluation as potential renal radiopharmaceuticals

  摘要：

  Novel diamide dimercaptide (N2S2) ligands 4, 5, and 8 have been synthesized and evaluated as potential renal radiopharmaceuticals. The target compounds were prepared in modest overall yields of 22 %, 19 %, and 20 %, respectively, using readily available starting materials. Following in situ deprotection, Tc-99m complexes of high radiochemical purity were obtained in excellent yield and were found to be stable for up to 6 h. The Tc-99 complex of ligand 8 was isolated as the AsPh4 salt. The X-ray crystallographic data for ([TcO(8)]AsPh4)-Tc-99 (space group P2(1)/n: Z = 4, a = 9.342(3) angstrom; b = 18.594(5) angstrom; c = 18.417(7) angstrom; beta, deg = 90.61(3); V, angstrom3 = 3199.1(20)) show that the Tc is bound to both thiolate sulfur atoms and to two deprotonated amide nitrogen atoms. The coordination geometry about the Tc is square-pyramidal with an -yl oxygen atom in the apical position. The Tc-N bond distances (2.002(12) and 1.984(12) angstrom), the Tc-S bond distances (2.300(5) and 2.286(5) angstrom), and the Tc-O bond distance (1.667(11) angstrom) are in good agreement with bond lengths reported for similar complexes. The carboxylate groups are not bonded to the Tc atom in the solid state, nor in CDCl3 solution, as evidenced by X-ray crystal data and solution NMR data, respectively. In the solid state, ([TcO(8)]AsPh4)-Tc-99 is monoanionic, therefore, at physiological pH, ([TcO(8)])-Tc-99m is presumably trianionic. Biodistribution studies performed in rats with the Tc-99m complexes revealed slow blood clearance and high muscle uptake for these agents. Modest hepatobiliary excretion was observed, and low quantities of the complexes were found in the heart, lungs, and spleen after 1 h. The urinary excretion of the Tc-99m complexes of ligands 4, 5, and 8 was found to be slow when compared to the excretion of [I-131]OIH in rats (22%, 22%, and 32% vs 85-86%, respectively). Protein binding of Tc-99m complexes of ligands 4,5, and 8 in both rat and monkey plasma was found to be similar to MAG3. While the synthetic schemes reported here supply facile routes to novel N2S2 ligands, biodistribution studies of the Tc-99m complexes performed on rats revealed slow renal excretion rates, accompanied by slow blood clearance and high uptake in muscle tissue. Preliminary planar imaging studies in monkeys also revealed slow renal excretion for these agents. The Tc-99m complexes evaluated here are poor candidates as renal radiopharmaceuticals.

  DOI：

  10.1021/jm00060a011

文献信息

• Dicarboxylate diamide dimercaptide (N2S2) technetium-99m complexes: synthesis and biological evaluation as potential renal radiopharmaceuticals
  作者：Daniel J. Canney、Jeffrey Billings、Lynn C. Francesconi、Yu Zhi Guo、Brian S. Haggerty、Arnold L. Rheingold、Hank F. Kung

  DOI：10.1021/jm00060a011

  日期：1993.4

  Novel diamide dimercaptide (N2S2) ligands 4, 5, and 8 have been synthesized and evaluated as potential renal radiopharmaceuticals. The target compounds were prepared in modest overall yields of 22 %, 19 %, and 20 %, respectively, using readily available starting materials. Following in situ deprotection, Tc-99m complexes of high radiochemical purity were obtained in excellent yield and were found to be stable for up to 6 h. The Tc-99 complex of ligand 8 was isolated as the AsPh4 salt. The X-ray crystallographic data for ([TcO(8)]AsPh4)-Tc-99 (space group P2(1)/n: Z = 4, a = 9.342(3) angstrom; b = 18.594(5) angstrom; c = 18.417(7) angstrom; beta, deg = 90.61(3); V, angstrom3 = 3199.1(20)) show that the Tc is bound to both thiolate sulfur atoms and to two deprotonated amide nitrogen atoms. The coordination geometry about the Tc is square-pyramidal with an -yl oxygen atom in the apical position. The Tc-N bond distances (2.002(12) and 1.984(12) angstrom), the Tc-S bond distances (2.300(5) and 2.286(5) angstrom), and the Tc-O bond distance (1.667(11) angstrom) are in good agreement with bond lengths reported for similar complexes. The carboxylate groups are not bonded to the Tc atom in the solid state, nor in CDCl3 solution, as evidenced by X-ray crystal data and solution NMR data, respectively. In the solid state, ([TcO(8)]AsPh4)-Tc-99 is monoanionic, therefore, at physiological pH, ([TcO(8)])-Tc-99m is presumably trianionic. Biodistribution studies performed in rats with the Tc-99m complexes revealed slow blood clearance and high muscle uptake for these agents. Modest hepatobiliary excretion was observed, and low quantities of the complexes were found in the heart, lungs, and spleen after 1 h. The urinary excretion of the Tc-99m complexes of ligands 4, 5, and 8 was found to be slow when compared to the excretion of [I-131]OIH in rats (22%, 22%, and 32% vs 85-86%, respectively). Protein binding of Tc-99m complexes of ligands 4,5, and 8 in both rat and monkey plasma was found to be similar to MAG3. While the synthetic schemes reported here supply facile routes to novel N2S2 ligands, biodistribution studies of the Tc-99m complexes performed on rats revealed slow renal excretion rates, accompanied by slow blood clearance and high uptake in muscle tissue. Preliminary planar imaging studies in monkeys also revealed slow renal excretion for these agents. The Tc-99m complexes evaluated here are poor candidates as renal radiopharmaceuticals.