1-Benzolsulfonyl-5.5-dimethyl-biguanidin | 91978-45-9

• 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-Benzolsulfonyl-5.5-dimethyl-biguanidin
• CAS: 91978-45-9
• 化学式: C₁₀H₁₅N₅O₂S
• 分子量: 269.327
• InChiKey: DQSMNNPRXWYCJL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.22
• 重原子数：
  18.0
• 可旋转键数：
  2.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  111.64
• 氢给体数：
  3.0
• 氢受体数：
  3.0

反应信息

• 作为产物：
  描述：

  盐酸二甲双胍 、 苯磺酰氯 在 sodium hydroxide 作用下， 以 丙酮 为溶剂， 生成 1-Benzolsulfonyl-5.5-dimethyl-biguanidin
  参考文献：
  名称：

  Hoekfelt,B.; Joensson,A., Journal of medicinal and pharmaceutical chemistry, 1962, vol. 5, p. 240 - 246

  摘要：

  DOI：

文献信息

• Novel Sulfonamide-Based Analogs of Metformin Exert Promising Anti-Coagulant Effects without Compromising Glucose-Lowering Activity
  作者：Magdalena Markowicz-Piasecka、Adrianna Sadkowska、Joanna Sikora、Marlena Broncel、Kristiina M. Huttunen

  DOI：10.3390/ph13100323

  日期：——

  Metformin, one of the most frequently prescribed oral anti-diabetic drugs, is characterized by multidirectional activity, including lipid lowering, cardio-protective and anti-inflammatory properties. This study presents synthesis and stability studies of 10 novel sulfonamide-based derivatives of metformin with alkyl substituents in the aromatic ring. The potential of the synthesized compounds as glucose-lowering agents and their effects on selected parameters of plasma and vascular hemostasis were examined. Compounds with two or three methyl groups in the aromatic ring (6, 7, 9, 10) significantly increased glucose uptake in human umbilical vein endothelial cells (HUVECs), e.g., 15.8 µmol/L for comp. 6 at 0.3 µmol/mL versus 11.4 ± 0.7 µmol/L for control. Basic coagulation studies showed that all examined compounds inhibit intrinsic coagulation pathway and the process of fibrin polymerization stronger than the parent drug, metformin, which give evidence of their greater anti-coagulant properties. Importantly, synthesized compounds decrease the activity of factor X, a first member of common coagulation pathway, while metformin does not affect coagulation factor X (FX) activity. A multiparametric clot formation and lysis test (CL-test) revealed that the examined compounds significantly prolong the onset of clot formation; however, they do not affect the overall potential of clot formation and fibrinolysis. Erythrotoxicity studies confirmed that none of the synthesized compounds exert an adverse effect on erythrocyte integrity, do not contribute to the massive hemolysis and do not interact strongly with the erythrocyte membrane. In summary, chemical modification of metformin scaffold into benzenesulfonamides containing alkyl substituents leads to the formation of potential dual-action agents with comparable glucose-lowering properties and stronger anti-coagulant activity than the parent drug, metformin.

  二甲双胍，是最常被开处方的口服抗糖尿病药物之一，具有多向活性，包括降脂、心脏保护和抗炎特性。本研究介绍了10种新型磺胺基双胍衍生物的合成和稳定性研究，这些衍生物在芳香环中带有烷基取代基。对合成化合物作为降糖剂的潜力以及它们对血浆和血管止血参数的影响进行了研究。在芳香环中带有两个或三个甲基基团的化合物（6、7、9、10）显著增加了人脐静脉内皮细胞（HUVECs）中的葡萄糖摄取，例如，comp. 6在0.3 µmol/mL时为15.8 µmol/L，而对照组为11.4 ± 0.7 µmol/L。基本凝血研究表明，所有检测的化合物都抑制内在凝血途径和纤维蛋白聚合过程，比原药物二甲双胍更强，这证明了它们具有更强的抗凝血特性。重要的是，合成的化合物降低了第一共同凝血途径成员X因子的活性，而二甲双胍不影响凝血因子X（FX）的活性。多参数凝血形成和溶解测试（CL-test）显示，检测的化合物显著延长了凝血形成的开始时间；然而，它们不影响凝血形成和纤溶的总体潜力。溶血毒性研究证实，合成的化合物中没有一种对红细胞完整性产生不良影响，不会导致大规模溶血，也不会与红细胞膜发生强烈相互作用。总之，将二甲双胍骨架进行化学修饰，形成含有烷基取代基的苯磺酰胺，导致形成具有可比较降糖特性和比原药物二甲双胍更强的抗凝血活性的潜在双重作用药物。