Synthesis and Study on the Phosphodiesterase Type 5 Inhibitory Activity of Bioisosteric Derivatives of Avanafil

FU Junjie; YONG Dianya; YU Shuitao; WANG Bin; WANG Yongjun; HU Jing; YIN Jian

doi:10.13748/j.cnki.issn1007-7693.20243251

FU Junjie, YONG Dianya, YU Shuitao, WANG Bin, WANG Yongjun, HU Jing, YIN Jian. Synthesis and Study on the Phosphodiesterase Type 5 Inhibitory Activity of Bioisosteric Derivatives of AvanafilJ. Chinese Journal of Modern Applied Pharmacy, 2026, 43(1): 1-14. DOI: 10.13748/j.cnki.issn1007-7693.20243251

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Synthesis and Study on the Phosphodiesterase Type 5 Inhibitory Activity of Bioisosteric Derivatives of Avanafil

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OBJECTIVE To design and synthesize novel avanafil derivatives and investigate their inhibitory activity on phosphodiesterase type 5(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 erectile dysfunction therapeutics.

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Synthesis and Study on the Phosphodiesterase Type 5 Inhibitory Activity of Bioisosteric Derivatives of Avanafil

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