Design and synthesis of xanthine analogues as potent and selective PDE5 inhibitors

We have discovered potent and selective xanthine PDE5 inhibitors. Compound 25 (PDE5 IC 50=0.6 nM, PDE6/PDE5=101) demonstrated similar functional efficacy and PK profile to Sildenafil (PDE5 IC 50=3.5 nM, PDE6/PDE5=7). We have discovered potent and selective xanthine PDE5 inhibitors. Compound 25 (PDE5...

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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2002-11, Vol.12 (21), p.3149-3152
Hauptverfasser:	Wang, Yuguang, Chackalamannil, Samuel, Hu, Zhiyong, Boyle, Craig D, Lankin, Claire M, Xia, Yan, Xu, Ruo, Asberom, Theodros, Pissarnitski, Dmitri, Stamford, Andrew W, Greenlee, William J, Skell, Jeffrey, Kurowski, Stanley, Vemulapalli, Subbarao, Palamanda, Jairam, Chintala, Madhu, Wu, Ping, Myers, Joyce, Wang, Peng
Format:	Artikel
Sprache:	eng
Schlagworte:	3',5'-Cyclic-GMP Phosphodiesterases Alkylation Animals Area Under Curve Biological and medical sciences Cyclic Nucleotide Phosphodiesterases, Type 5 Drug Design Electric Stimulation Genital system. Reproduction In Vitro Techniques Male Medical sciences Muscle Contraction - drug effects Muscle Relaxation - drug effects Penis - drug effects Pharmacology. Drug treatments Phosphodiesterase Inhibitors - chemical synthesis Phosphodiesterase Inhibitors - pharmacology Phosphoric Diester Hydrolases - metabolism Piperazines - pharmacology Purines Rabbits Sildenafil Citrate Structure-Activity Relationship Sulfones Xanthines - chemical synthesis Xanthines - pharmacology
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Zusammenfassung:	We have discovered potent and selective xanthine PDE5 inhibitors. Compound 25 (PDE5 IC 50=0.6 nM, PDE6/PDE5=101) demonstrated similar functional efficacy and PK profile to Sildenafil (PDE5 IC 50=3.5 nM, PDE6/PDE5=7). We have discovered potent and selective xanthine PDE5 inhibitors. Compound 25 (PDE5 IC 50=0.6 nM, PDE6/PDE5=101) demonstrated similar functional efficacy and PK profile to Sildenafil (PDE5 IC 50=3.5 nM, PDE6/PDE5=7).
ISSN:	0960-894X 1464-3405
DOI:	10.1016/S0960-894X(02)00646-7