Literature

Abstract

Synthesis of new sildenafil analogues containing a phosphonate group in the 5(')-sulfonamide moiety of the phenyl ring, 12a-e, 13a-d, and 14a-d, and evaluation of their in vitro PDE5 inhibitory activity are disclosed. Enzyme assays revealed that maximum 10-fold increase in PDE5 inhibitory activity, compared with sildenafil, was achieved by introducing a phosphonate group in the 5(')-sulfonamide moiety. Docking model of (PDE5: 12d) complex shows that the PDE5-bound conformation of 12d matches completely with that of sildenafil, while 12d is partially overlapped with cGMP with ethyl phosphonate group of 12d superimposed onto the cyclic phosphate group of cGMP.

DOI： 10.1016/j.bmcl.2004.02.040

Synthesis and phosphodiesterase 5 inhibitory activity of new sildenafil analogues containing a phosphonate group in the 5 ′ -sulfonamide moiety of phenyl ring

Bioorganic & Medicinal Chemistry Letters 2004.0

Synthesis and Pharmacological Evaluations of Sildenafil Analogues for Treatment of Erectile Dysfunction

Journal of Medicinal Chemistry 2008.0

Discovery of novel pyrazolopyrimidinone analogs as potent inhibitors of phosphodiesterase type-5

Bioorganic & Medicinal Chemistry 2015.0

Design and synthesis of pyrazolo[3,4-d]pyrimidinone derivatives: Discovery of selective phosphodiesterase-5 inhibitors

Bioorganic & Medicinal Chemistry Letters 2020.0

3D-QSAR studies on sildenafil analogues, selective phosphodiesterase 5 inhibitors

Bioorganic & Medicinal Chemistry Letters 2007.0

Optimization of Substituted N-3-Benzylimidazoquinazolinone Sulfonamides as Potent and Selective PDE5 Inhibitors