| 引用本文: | 傅俊杰,雍典雅,于水涛,王彬,王勇军,胡静,尹健.阿伐那非生物电子等排衍生物的合成及PDE5抑制活性研究[J].中国现代应用药学,2026,43(1):43-56. |
| Fu Junjie,Yong Dianya,Yu Shuitao,Wang Bin,Wang Yongjun,Hu Jing,Yin Jian.Synthesis and PDE5 Inhibitory Activity of Bioisosteric Derivatives of Avanafil[J].Chin J Mod Appl Pharm(中国现代应用药学),2026,43(1):43-56. |
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| 阿伐那非生物电子等排衍生物的合成及PDE5抑制活性研究 |
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傅俊杰1, 雍典雅1, 于水涛2, 王彬3, 王勇军2,3, 胡静4, 尹健1,5
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1.江南大学生物工程学院糖化学与生物技术教育部重点实验室;2.常州亚邦制药有限公司;3.江苏亚邦爱普森药业有限公司;4.江南大学无锡医学院;5.江南大学生命科学与健康工程学院
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| 摘要: |
| 目的 设计合成新型阿伐那非衍生物，并考察其对PDE5的抑制活性。方法 以阿伐那非为先导化合物，利用生物电子等排原理设计合成了20个阿伐那非衍生物，通过基于荧光偏振技术的PDE5酶活性测试，对衍生物的体外PDE5抑制活性进行定量筛选。结果 硫代酰胺衍生物I-2、I-4、I-5和I-7的PDE5抑制活性相对较好，但仍低于阿伐那非；氯代衍生物II-1和II-6的PDE5抑制活性较为突出，其IC50值与阿伐那非相当。结论 氯代衍生物II-1的PDE5抑制活性最好，值得进一步深入研究；构效关系分析为基于阿伐那非的PDE5抑制剂的结构优化提供了有益参考，为新型ED治疗药物的研发奠定了基础。 |
| 关键词: PDE5抑制剂 阿伐那非 生物电子等排体 硫代酰胺 |
| DOI： |
| 分类号:R914.2 |
| 基金项目:国家自然科学基金项目（面上项目，重点项目，重大项目） |
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| Synthesis and PDE5 Inhibitory Activity of Bioisosteric Derivatives of Avanafil |
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Fu Junjie1, Yong Dianya1, Yu Shuitao2, Wang Bin3, Wang Yongjun2,3, Hu Jing4, Yin Jian1,5
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1.Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University;2.Changzhou Yabang Pharmaceutical Co., Ltd;3.Jiangsu Yabang Aipusen Pharmaceutical Co., Ltd;4.Wuxi Schoool of Medicine, Jiangnan University;5.School of Life Sciences and Health Engineering, Jiangnan University
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| Abstract: |
| To design and synthesize novel avanafil derivatives and investigate their inhibitory activity on PDE5. METHODS Using Avanafil as a lead compound, 20 avanafil derivatives were designed and synthesized based on the bioisosterism principle. The in vitro inhibitory activity of these derivatives on PDE5 was quantitatively screened using a fluorescence polarization-based PDE5 enzyme activity assay. RESULTS Among the derivatives, thioamide derivatives I-2, I-4, I-5, and I-7 demonstrated relatively good PDE5 inhibitory activity, though still lower than Avanafil. The chloro derivatives II-1 and II-6 showed notably strong PDE5 inhibitory activity, with IC50 values comparable to Avanafil. CONCLUSION Chloro derivative II-1 exhibited the best PDE5 inhibitory activity, meriting further in-depth study. The structure-activity relationship analysis provides valuable insights for structural optimization of PDE5 inhibitors based on Avanafil, laying a foundation for the development of novel ED therapeutics. |
| Key words: PDE5 inhibitor Avanafil bioisostere thioamide |
