1. Substituted Pyrazolopyridopyridazines as Orally Bioavailable Potent and Selective PDE5 Inhibitors: Potential Agents for Treatment of Erectile Dysfunction
- Author
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Laurie Seliger, Jian Wang, Ronald Pongrac, Helen J. Mason, Bruce Beyer, Andrew Henwood, John Krupinski, Ximao Wu, John E. Macor, Saeho Chong, Rongan Zhang, Pam Ferrer, Diane E. Normandin, Guixue Yu, Leonard P. Adam, William G. Humphrey, and Bin He
- Subjects
Male ,medicine.medical_specialty ,Sildenafil ,Administration, Oral ,Biological Availability ,Blood Pressure ,Structure-Activity Relationship ,chemistry.chemical_compound ,Dogs ,Erectile Dysfunction ,Pharmacokinetics ,3',5'-Cyclic-GMP Phosphodiesterases ,Oral administration ,In vivo ,Internal medicine ,Drug Discovery ,medicine ,Animals ,Enzyme Inhibitors ,Adverse effect ,Cyclic Nucleotide Phosphodiesterases, Type 5 ,biology ,medicine.disease ,In vitro ,Rats ,Pyridazines ,Erectile dysfunction ,Endocrinology ,chemistry ,Enzyme inhibitor ,biology.protein ,Molecular Medicine ,Female ,Rabbits ,Penis - Abstract
Novel pyrazolopyridopyridazine derivatives have been prepared as potent and selective PDE5 inhibitors. Compound 6 has been identified as a more potent and selective PDE5 inhibitor than sildenafil (1). It is as efficacious as sildenafil in in vitro and in vivo PDE5 inhibition models, and it is orally bioavailable in rats and dogs. The superior isozyme selectivity of 6 is expected to exert less adverse effects in humans when used for erectile dysfunction treatment.
- Published
- 2003
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