5-{5-[(4-benzylpiperazin-1-yl)methyl]-1,3,4-oxadiazol-2-yl}-2-benzylthio-4-chlorobenzenesulfonamide

• 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: 5-{5-[(4-benzylpiperazin-1-yl)methyl]-1,3,4-oxadiazol-2-yl}-2-benzylthio-4-chlorobenzenesulfonamide
• 英文别名: 5-[5-[(4-Benzylpiperazin-1-yl)methyl]-1,3,4-oxadiazol-2-yl]-2-benzylsulfanyl-4-chlorobenzenesulfonamide；5-[5-[(4-benzylpiperazin-1-yl)methyl]-1,3,4-oxadiazol-2-yl]-2-benzylsulfanyl-4-chlorobenzenesulfonamide
• 化学式: C₂₇H₂₈ClN₅O₃S₂
• 分子量: 570.136
• InChiKey: RXWMIDCHADMLTA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  38
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  139
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2,4-dichloro-5-(carbazoyl)benzenesulfonamide 在 四丁基碘化铵 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 乙醇 、 水 、 乙腈 为溶剂， 反应 42.0h， 生成 5-{5-[(4-benzylpiperazin-1-yl)methyl]-1,3,4-oxadiazol-2-yl}-2-benzylthio-4-chlorobenzenesulfonamide
  参考文献：
  名称：

  Novel 2-benzylthio-5-(1,3,4-oxadiazol-2-yl)benzenesulfonamides with anticancer activity: Synthesis, QSAR study, and metabolic stability

  摘要：

  A series of novel 2-benzylthio-4-chloro-5-(5-substituted 1,3,4-oxadiazol-2-yl)benzenesulfonamides (4 27) have been synthesized as potential anticancer agents. MIT assay was carried out to determine the cytotoxic activity against three human cancer cell lines: colon cancer HCT-116, breast cancer MCF-7 and cervical cancer HeLa as well as to determine the influence on human keratinocyte cell line HaCaT. Relatively high (IC50: 7-17 mu M) cytostatic activity and selectivity against HeLa cell line was found for compounds 6, 7, 9-11 and 16. While compounds 23-27 bearing styryl moieties attached to a 1,3,4-oxadiazole ring at position 5, exhibited significant activity against two and/or three cancer cell lines with IC50: 11-29 mu M. Further quantitative structure-activity relationships based on molecular descriptors calculated by DRAGON software, were investigated by Orthogonal Projections to Latent Structures (OPLS) technique and Variable Influence on Projection (VIP) analysis. Considering molecular descriptors with the highest influence on projection (highest VIP values) lipophilicity of tested compounds was pointed as main factor affecting activity towards HCT-116 cell line, while structural parameters associated with presence of styryl substituent in position 5 of 1,3,4-oxadiazole ring were identified as essential for activity towards MCF-7 breast cancer. In vitro tests for metabolic stability in the presences of pooled human liver microsomes and NADPH showed that some of the most active compounds 26 and 27 presented favorable metabolic stability with t(1/2) in the range of 28.1-36.0 min. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.03.039

文献信息

• Novel 2-benzylthio-5-(1,3,4-oxadiazol-2-yl)benzenesulfonamides with anticancer activity: Synthesis, QSAR study, and metabolic stability
  作者：Jarosław Sławiński、Krzysztof Szafrański、Aneta Pogorzelska、Beata Żołnowska、Anna Kawiak、Katarzyna Macur、Mariusz Belka、Tomasz Bączek

  DOI：10.1016/j.ejmech.2017.03.039

  日期：2017.5

  A series of novel 2-benzylthio-4-chloro-5-(5-substituted 1,3,4-oxadiazol-2-yl)benzenesulfonamides (4 27) have been synthesized as potential anticancer agents. MIT assay was carried out to determine the cytotoxic activity against three human cancer cell lines: colon cancer HCT-116, breast cancer MCF-7 and cervical cancer HeLa as well as to determine the influence on human keratinocyte cell line HaCaT. Relatively high (IC50: 7-17 mu M) cytostatic activity and selectivity against HeLa cell line was found for compounds 6, 7, 9-11 and 16. While compounds 23-27 bearing styryl moieties attached to a 1,3,4-oxadiazole ring at position 5, exhibited significant activity against two and/or three cancer cell lines with IC50: 11-29 mu M. Further quantitative structure-activity relationships based on molecular descriptors calculated by DRAGON software, were investigated by Orthogonal Projections to Latent Structures (OPLS) technique and Variable Influence on Projection (VIP) analysis. Considering molecular descriptors with the highest influence on projection (highest VIP values) lipophilicity of tested compounds was pointed as main factor affecting activity towards HCT-116 cell line, while structural parameters associated with presence of styryl substituent in position 5 of 1,3,4-oxadiazole ring were identified as essential for activity towards MCF-7 breast cancer. In vitro tests for metabolic stability in the presences of pooled human liver microsomes and NADPH showed that some of the most active compounds 26 and 27 presented favorable metabolic stability with t(1/2) in the range of 28.1-36.0 min. (C) 2017 Elsevier Masson SAS. All rights reserved.