1-((4-methoxyphenyl)sulfonyl)pyrrolidine-2-carbonyl chloride

• 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: 1-((4-methoxyphenyl)sulfonyl)pyrrolidine-2-carbonyl chloride
• 英文别名: 1-(4-Methoxyphenyl)sulfonylpyrrolidine-2-carbonyl chloride；1-(4-methoxyphenyl)sulfonylpyrrolidine-2-carbonyl chloride
• 化学式: C₁₂H₁₄ClNO₄S
• 分子量: 303.766
• InChiKey: VFOFMOGCWLUWLG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  72.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-((4-methoxyphenyl)sulfonyl)pyrrolidine-2-carbonyl chloride 在 羟胺 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 N-hydroxy-1-[4-methoxybenzenesulfonyl]-pyrrolidine-2(S)-carboxamide
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Potent Thiazine- and Thiazepine-Based Matrix Metalloproteinase Inhibitors

  摘要：

  The synthesis and enzyme inhibition data for a series of thiazine- and thiazepine-based matrix metalloproteinase (MMP) inhibitors are described. The thiazine- and thiazepine-based inhibitors were discovered by optimization of hetererocyclic sulfonamide-based inhibitors. The most potent series of inhibitors was obtained by modification of the amino acid D-penicillamine. This amino acid provides a gem-dimethyl group on the thiazine or thiazepine ring which has a dramatic effect on the in vitro potency of this series. In particular, the sulfide 4a and the sulfone 5a were potent, broad-spectrum inhibitors of the MMPs with IC50's against MMP-1 of 0.8 and 1.9 nM, respectively. The binding mode of this novel thiazepine-based series of MMP inhibitors was established based on X-ray crystallography of the complex of stromelysin and 4a.

  DOI：

  10.1021/jm990330y
• 作为产物：
  描述：

  N-((4-methoxyphenyl)sulfonyl)proline 在 氯化亚砜 作用下， 反应 4.0h， 以82%的产率得到1-((4-methoxyphenyl)sulfonyl)pyrrolidine-2-carbonyl chloride
  参考文献：
  名称：

  Design, Synthesis, Molecular Docking and in vitro Evaluation of N-(4-Methoxyphenylsulfonyl)pyrrolidine-2-carboxylic Acid Analogues as Antiangiogenic and Anticancer Agents on Multiple Myeloma

  摘要：

  一系列N-(4-甲氧基苯基磺酰基)吡咯烷-2-羧酸类似物被设计为沙利度胺的主要代谢产物N-(邻羧基苯甲酰)-D,L-谷氨酸的生物同源体。化合物2b、2d、2f、2i和2k通过MTS分析在多发性骨髓瘤(RPMI 8226)上展现了抗癌活性，并通过MTT分析在HUVEC细胞系上进行了初级抗血管生成活性测试。化合物2f由于对正常上皮细胞具有细胞毒性而被排除在进一步研究之外。2b、2d、2i和2k被发现具有初级抗血管生成活性，同时在MTT分析中对正常vero细胞具有低细胞毒性，表明对高度血管生成的多发性骨髓瘤具有选择性细胞毒性。对化合物2b、2d、2i和2k在HUVECs上的抗增殖分析采用了尝试蓝染色排除法。化合物2b的分子对接研究计算出结合能为-89.78 kcal/mol，并展示了与关键氨基酸残基形成的五个氢键。这些化合物是进行进一步研究的潜在候选药物。

  DOI：

  10.14233/ajchem.2020.22957

文献信息

• Design, Synthesis, Molecular Docking and in vitro Evaluation of N-(4-Methoxyphenylsulfonyl)pyrrolidine-2-carboxylic Acid Analogues as Antiangiogenic and Anticancer Agents on Multiple Myeloma
  作者：K. Sarker、A. Ghosh、S. Mishra、A. Saha、S. Sen

  DOI：10.14233/ajchem.2020.22957

  日期：——

  A series of N-(4-methoxyphenylsulfonyl)pyrrolidine-2-carboxylic acid analogs were designed as bioisosteres of a major metabolite of thalidomide, i.e., N-(o-carboxybenzoyl)-D,L-glutamic acid. Compounds 2b, 2d, 2f, 2i and 2k exhibited anticancer activity on multiple myeloma (RPMI 8226) by MTS assay and were tested for primary antiangiogenic activity on HUVEC cell line by MTT assay. Compound 2f was excluded from further study as it was found to be cytotoxic to normal epithelial cells. 2b, 2d, 2i and 2k were found to have primary antiangiogenic activity along with low cytotoxicity on normal vero cells in MTT assay indicating selective cytotoxicity towards highly angiogenic multiple myeloma. Antiproliferative assay of compounds 2b, 2d, 2i and 2k on HUVECs was carried out using the dye exclusion method with trypan blue. Molecular docking study of compound 2b calculated the binding energy -89.78 kcal/mol and displayed five hydrogen bonds with critical amino acid residues. The compounds are potential candidate drugs for advanced investigations.

  一系列N-(4-甲氧基苯基磺酰基)吡咯烷-2-羧酸类似物被设计为沙利度胺的主要代谢产物N-(邻羧基苯甲酰)-D,L-谷氨酸的生物同源体。化合物2b、2d、2f、2i和2k通过MTS分析在多发性骨髓瘤(RPMI 8226)上展现了抗癌活性，并通过MTT分析在HUVEC细胞系上进行了初级抗血管生成活性测试。化合物2f由于对正常上皮细胞具有细胞毒性而被排除在进一步研究之外。2b、2d、2i和2k被发现具有初级抗血管生成活性，同时在MTT分析中对正常vero细胞具有低细胞毒性，表明对高度血管生成的多发性骨髓瘤具有选择性细胞毒性。对化合物2b、2d、2i和2k在HUVECs上的抗增殖分析采用了尝试蓝染色排除法。化合物2b的分子对接研究计算出结合能为-89.78 kcal/mol，并展示了与关键氨基酸残基形成的五个氢键。这些化合物是进行进一步研究的潜在候选药物。
• Design, Synthesis, and Biological Evaluation of Potent Thiazine- and Thiazepine-Based Matrix Metalloproteinase Inhibitors
  作者：Neil G. Almstead、Rimma S. Bradley、Stanislaw Pikul、Biswanath De、Michael G. Natchus、Yetunde O. Taiwo、Fei Gu、Lisa E. Williams、Barbara A. Hynd、Michael J. Janusz、C. Michelle Dunaway、Glen E. Mieling

  DOI：10.1021/jm990330y

  日期：1999.11.1

  The synthesis and enzyme inhibition data for a series of thiazine- and thiazepine-based matrix metalloproteinase (MMP) inhibitors are described. The thiazine- and thiazepine-based inhibitors were discovered by optimization of hetererocyclic sulfonamide-based inhibitors. The most potent series of inhibitors was obtained by modification of the amino acid D-penicillamine. This amino acid provides a gem-dimethyl group on the thiazine or thiazepine ring which has a dramatic effect on the in vitro potency of this series. In particular, the sulfide 4a and the sulfone 5a were potent, broad-spectrum inhibitors of the MMPs with IC50's against MMP-1 of 0.8 and 1.9 nM, respectively. The binding mode of this novel thiazepine-based series of MMP inhibitors was established based on X-ray crystallography of the complex of stromelysin and 4a.