Chin. J. Org. Chem. ›› 2016, Vol. 36 ›› Issue (3): 490-501.DOI: 10.6023/cjoc201510006 Previous Articles     Next Articles



赵飞a,b, 王江a, 丁晓a, 舒双杰a, 柳红a   

  1. a 中国科学院上海药物研究所 受体结构与功能重点实验室 上海 201203;
    b 成都大学 四川抗菌素工业研究所抗生素研究与再评价四川省重点实验室 成都 610052
  • 收稿日期:2015-10-09 修回日期:2015-11-13 发布日期:2015-12-04
  • 通讯作者: 柳红
  • 基金资助:

    国家自然科学基金(No. 21372235)资助项目.

Application of Sulfonyl in Drug Design

Zhao Feia,b, Wang Jianga, Ding Xiaoa, Shu Shuangjiea, Liu Honga   

  1. a Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203;
    b Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, Chengdu University, Chengdu 610052
  • Received:2015-10-09 Revised:2015-11-13 Published:2015-12-04
  • Supported by:

    Project supported by the National Natural Science Foundation of China (No. 21372235).

Sulfonyl-containing compounds comprise a substantial proportion in the therapeutic drugs. It is an important strategy to introduce sulfonyl group into the small molecules for structure-based medicinal chemistry, the application of sulfonyl group in drug design is reviewed in this paper. Structurally, sulfonyl group has similar properties in molecular size and charge distribution with carbonyl, carboxyl, tetrazolium and phosphate group, so it can be introduced into the drug molecules as their bioisostere in order to remain or improve activity. Sulfonyl group possesses unique physicochemical properties, and the introduction of sulfonyl group can also modulate the solubility and acid-base property of the drug molecules. Sulfonyl group can offer two hydrogen-bond receptors, and reasonable introduction of sulfonyl group can enhance the binding affinity of the drug molecules with the targeted proteins to improve activity through hydrogen bond interactions. What's more, sulfonyl group is relatively stable in terms of structure, the introduction of sulfonyl group can increase the metabolic stability of drugs to prolong the duration of action by blocking metabolically labile sites, improve the pharmacokinetic properties of the drug molecules to elevate the bioavailability. Sulfonyl group belongs to polar groups, which can also increase the polarity of the drug molecules to diminish hERG activity.

Key words: sulfonyl, drug design, lead optimization