N-(5-ethyl-1,3,4-thiadiazol-2-yl)-3-[4-[(4-fluorophenyl)aminosulfonyl]-phenyl]propanamide | 1201912-33-5

• 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: N-(5-ethyl-1,3,4-thiadiazol-2-yl)-3-[4-[(4-fluorophenyl)aminosulfonyl]-phenyl]propanamide
• 英文别名: N-(5-ethyl-1,3,4-thiadiazol-2-yl)-3-[4-[(4-fluorophenyl)sulfamoyl]phenyl]propanamide
• CAS: 1201912-33-5
• 化学式: C₁₉H₁₉FN₄O₃S₂
• 分子量: 434.515
• InChiKey: LYCLXIQEHQSLKK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  138
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  3-苯丙酸甲酯 在 吡啶 、 氯磺酸 、 草酰氯 、 lithium hydroxide monohydrate 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 15.5h， 生成 N-(5-ethyl-1,3,4-thiadiazol-2-yl)-3-[4-[(4-fluorophenyl)aminosulfonyl]-phenyl]propanamide
  参考文献：
  名称：

  Design and synthesis of small molecular dual inhibitor of falcipain-2 and dihydrofolate reductase as antimalarial agent

  摘要：

  Resistance of malaria parasites has quickly developed to almost all used antimalarial drugs. Accordingly, the discovery of new effective drugs to counter the spread of malaria parasites that are resistant to existing agents, especially acting on multi-targets, is an urgent need. The cysteine protease falcipain-2 (FP-2) and dihydrofolate reductase (DHFR) play crucial roles in the Plasmodium life cycle. In this study, a series of first-gereration small molecular dual inhibitor of FP-2 and DHFR have been designed and synthesized based on the lead compound 1, which was randomly identified by screening FP-2 inhibitors in our laboratory. Six compounds (2f-g, 2j, and 2m-o) showed improved dual inhibitory activities against FP-2 (IC50 = 2.7-13.2 mu M) and DHFR (IC50 = 1.8-19.8 mu M), and the inhibitory capability of compound 2o against FP-2 and DHFR were increased similar to 8 and similar to 6 times than that of compound 1, respectively. Moreover, compound 20 exhibited moderate in vivo antimalarial activity in a dose dependent fashion, its safety and survival rate were slightly better than that of positive drug. The preliminary SAR was obtained, meanwhile, molecular modeling result provided the key structural information to maintain the dual inhibitory activity, and was helpful for future dual inhibitors design. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.12.011

文献信息

• Design and synthesis of small molecular dual inhibitor of falcipain-2 and dihydrofolate reductase as antimalarial agent
  作者：Huang Huang、Weiqiang Lu、Xi Li、Xiaoli Cong、Hongmei Ma、Xiaofeng Liu、Yu Zhang、Peng Che、Ruoqun Ma、Honglin Li、Xu Shen、Hualiang Jiang、Jin Huang、Jin Zhu

  DOI：10.1016/j.bmcl.2011.12.011

  日期：2012.1

  Resistance of malaria parasites has quickly developed to almost all used antimalarial drugs. Accordingly, the discovery of new effective drugs to counter the spread of malaria parasites that are resistant to existing agents, especially acting on multi-targets, is an urgent need. The cysteine protease falcipain-2 (FP-2) and dihydrofolate reductase (DHFR) play crucial roles in the Plasmodium life cycle. In this study, a series of first-gereration small molecular dual inhibitor of FP-2 and DHFR have been designed and synthesized based on the lead compound 1, which was randomly identified by screening FP-2 inhibitors in our laboratory. Six compounds (2f-g, 2j, and 2m-o) showed improved dual inhibitory activities against FP-2 (IC50 = 2.7-13.2 mu M) and DHFR (IC50 = 1.8-19.8 mu M), and the inhibitory capability of compound 2o against FP-2 and DHFR were increased similar to 8 and similar to 6 times than that of compound 1, respectively. Moreover, compound 20 exhibited moderate in vivo antimalarial activity in a dose dependent fashion, its safety and survival rate were slightly better than that of positive drug. The preliminary SAR was obtained, meanwhile, molecular modeling result provided the key structural information to maintain the dual inhibitory activity, and was helpful for future dual inhibitors design. (C) 2011 Elsevier Ltd. All rights reserved.