A solid-phase approach towards the synthesis of PDE5 inhibitors.
PDE5 inhibitors based upon the xanthine scaffold 8 have been expediently synthesized using a solid-phase route. Attachment of the xanthine scaffold 8 using the Rink chloride linker 4 and N-1 functionalization using Mitsunobu chemistry is described. A library of compounds was produced in multi-milligram quantities with excellent purities and acceptable yields. The compounds were tested for their PDE5 inhibitory activity.
Novartis Horsham Research Centre, Wimblehurst Road, Horsham, West Sussex RH12 5AB, UK.
David
D
Beer
Gurdip
G
Bhalay
Andrew
A
Dunstan
Angela
A
Glen
Sandra
S
Haberthuer
Heinz
H
Moser
D015106:3',5'-Cyclic-GMP Phosphodiesterases; D020650:Combinatorial Chemistry Techniques; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D016208:Databases, Factual; D007202:Indicators and Reagents / Q000737:chemistry; D019906:Nuclear Magnetic Resonance, Biomolecular; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D013329:Structure-Activity Relationship; D019820:Xanthine / Q000737:chemistry*
D007202:Indicators and Reagents; D010726:Phosphodiesterase Inhibitors; D019820:Xanthine; D010727:Phosphoric Diester Hydrolases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5