Abstract
Synthesis of furoyl and benzofuroyl pyrroloquinolones as potent and selective PDE5 inhibitors was reported. Their in vitro potencies in inhibiting PDE5 and selectivity in inhibiting other PDE isozymes (PDE1-4 and PDE6) were evaluated. Some of these compounds are more potent than sildenafil with better selectivity toward PDE1 and PDE6. Incorporation of solublizing groups resulted in bioavailable analogues. Selected compounds showed in vivo efficacy in anesthetized dog model for penile erection.
MeSH terms
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3',5'-Cyclic-GMP Phosphodiesterases / antagonists & inhibitors*
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Animals
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Biological Availability
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Cell Line
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Cyclic GMP / biosynthesis
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Cyclic Nucleotide Phosphodiesterases, Type 5
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Dogs
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Erectile Dysfunction / drug therapy
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Furans / chemical synthesis*
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Furans / chemistry
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Furans / pharmacology
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Isoenzymes / antagonists & inhibitors
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Male
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Penile Erection / drug effects
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Quinolones / chemical synthesis*
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Quinolones / chemistry
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Quinolones / pharmacology
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Rats
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Structure-Activity Relationship
Substances
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Furans
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Isoenzymes
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Quinolones
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3',5'-Cyclic-GMP Phosphodiesterases
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Cyclic Nucleotide Phosphodiesterases, Type 5
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Pde5a protein, rat
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Cyclic GMP