2-(thiophene-2-sulfonamido)pentanedioic acid | 82068-25-5

• 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: 2-(thiophene-2-sulfonamido)pentanedioic acid
• 英文别名: (2S)-2-(thiophen-2-ylsulfonylamino)pentanedioic acid
• CAS: 82068-25-5
• 化学式: C₉H₁₁NO₆S₂
• mdl: MFCD16380237
• 分子量: 293.321
• InChiKey: HFJOKEVEWJWFKN-LURJTMIESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  157
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-(thiophene-2-sulfonamido)pentanedioic acid 在 氯化亚砜 作用下， 以 苯 为溶剂， 反应 4.0h， 生成 N1,N5-dihexyl-2-(thiophene-2-sulfonamido)pentanediamide
  参考文献：
  名称：

  一些沙利度胺代谢物作为针对多发性骨髓瘤的选择性细胞毒性和抗血管生成剂的基于类似物的设计、合成、生物学评估和分子对接

  摘要：

  摘要 本文描述了沙利度胺代谢物的一些生物等排体对多发性骨髓瘤的抗血管生成和抗癌活性的合成和评价。四种化合物，2-(噻吩-2-磺酰胺)戊二酸二乙酯、N 1, N 5-二乙基-2-(噻吩-2-磺酰胺)戊二酰胺、N 1, N 5-二己基-2-(噻吩-2-磺酰胺) ) 戊二酰胺和N -(1,5-dioxo-1,5-bis(2-phenylhydrazinyl)pentan-2-yl)thiophene-2-sulfonamide 对人多发性骨髓瘤细胞系 (RPMI8226) 具有细胞毒性作用，IC 50（以 μM 为单位）值分别为 3.33、0.75、1.23 和 3.28。对人脐静脉内皮细胞 (HUVEC) 和正常非洲绿猴肾上皮细胞 (Vero 细胞系) 的体外研究得出结论，这些化合物具有抗血管生成特性，并且对癌细胞具有选择性细胞毒性。除N- (1,5-dioxo-1,5-bis(2-pheny

  DOI：

  10.1134/s1068162022010022
• 作为产物：
  描述：

  di-tert-butyl (thiophen-2-ylsulfonyl)-L-glutamate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以75%的产率得到2-(thiophene-2-sulfonamido)pentanedioic acid
  参考文献：
  名称：

  N-Substituted Glutamyl Sulfonamides as Inhibitors of Glutamate Carboxypeptidase II (GCP2)

  摘要：

  Glutamate carboxypeptidase II (GCP2) is a membrane‐bound cell‐surface peptidase which is implicated in several neurological disorders and is also over‐expressed in prostate tumor cells. There is a significant interest in the inhibition of GCP2 as a means of neuroprotection, while GCP2 inhibition as a method to treat prostate cancer remains a topic of further investigation. The key zinc‐binding functional group of the well‐characterized classes of GCP2 inhibitors (phosphonates and phosphoramidates) is tetrahedral and negatively charged at neutral pH, while glutamyl urea class of inhibitors possesses a planar and neutral zinc‐binding group. This study introduces a new class of GCP2 inhibitors, N‐substituted glutamyl sulfonamides, which possess a neutral tetrahedral zinc‐binding motif. A library containing 15 secondary sulfonamides and 4 tertiary (N‐methyl) sulfonamides was prepared and evaluated for inhibitory potency against purified GCP2 enzyme activity. While most inhibitors lacked potency at 100 μm, short alkyl sulfonamides exhibited promising low micromolar potency, with the optimal inhibitor in this series being glutamyl N‐(propylsulfonamide) (2g). Lastly, molecular docking was used to develop a model to formulate an explanation for the relative inhibitory potencies employed for this class of inhibitors.

  DOI：

  10.1111/j.1747-0285.2011.01085.x

文献信息

• N-Substituted Glutamyl Sulfonamides as Inhibitors of Glutamate Carboxypeptidase II (GCP2)
  作者：Brian R. Blank、Pinar Alayoglu、William Engen、Joseph K. Choi、Clifford E. Berkman、Marc O. Anderson

  DOI：10.1111/j.1747-0285.2011.01085.x

  日期：2011.4

  Glutamate carboxypeptidase II (GCP2) is a membrane‐bound cell‐surface peptidase which is implicated in several neurological disorders and is also over‐expressed in prostate tumor cells. There is a significant interest in the inhibition of GCP2 as a means of neuroprotection, while GCP2 inhibition as a method to treat prostate cancer remains a topic of further investigation. The key zinc‐binding functional group of the well‐characterized classes of GCP2 inhibitors (phosphonates and phosphoramidates) is tetrahedral and negatively charged at neutral pH, while glutamyl urea class of inhibitors possesses a planar and neutral zinc‐binding group. This study introduces a new class of GCP2 inhibitors, N‐substituted glutamyl sulfonamides, which possess a neutral tetrahedral zinc‐binding motif. A library containing 15 secondary sulfonamides and 4 tertiary (N‐methyl) sulfonamides was prepared and evaluated for inhibitory potency against purified GCP2 enzyme activity. While most inhibitors lacked potency at 100 μm, short alkyl sulfonamides exhibited promising low micromolar potency, with the optimal inhibitor in this series being glutamyl N‐(propylsulfonamide) (2g). Lastly, molecular docking was used to develop a model to formulate an explanation for the relative inhibitory potencies employed for this class of inhibitors.
• Analogue Based Design, Synthesis, Biological Evaluation, and Molecular Docking of Some Thalidomide Metabolites as Selective Cytotoxic and Antiangiogenic Agents against Multiple Myeloma
  作者：Abhijit Saha、Koushik Sarker、Avijit Ghosh、Suvasish Mishra、Subrata Sen

  DOI：10.1134/s1068162022010022

  日期：2022.2

  Abstract The synthesis and evaluation of some bioisosteres of thalidomide metabolites for antiangiogenic and anticancer activity on multiple myeloma are described in this article. Four compounds, diethyl 2-(thiophene-2-sulfonamido) pentanedioate, N1,N5-diethyl-2-(thiophene-2-sulfonamido) pentanediamide, N1,N5-dihexyl-2-(thiophene-2-sulfonamido) pentanediamide, and N-(1,5-dioxo-1,5-bis(2-phenylhydr

  摘要 本文描述了沙利度胺代谢物的一些生物等排体对多发性骨髓瘤的抗血管生成和抗癌活性的合成和评价。四种化合物，2-(噻吩-2-磺酰胺)戊二酸二乙酯、N 1, N 5-二乙基-2-(噻吩-2-磺酰胺)戊二酰胺、N 1, N 5-二己基-2-(噻吩-2-磺酰胺) ) 戊二酰胺和N -(1,5-dioxo-1,5-bis(2-phenylhydrazinyl)pentan-2-yl)thiophene-2-sulfonamide 对人多发性骨髓瘤细胞系 (RPMI8226) 具有细胞毒性作用，IC 50（以 μM 为单位）值分别为 3.33、0.75、1.23 和 3.28。对人脐静脉内皮细胞 (HUVEC) 和正常非洲绿猴肾上皮细胞 (Vero 细胞系) 的体外研究得出结论，这些化合物具有抗血管生成特性，并且对癌细胞具有选择性细胞毒性。除N- (1,5-dioxo-1,5-bis(2-pheny