1-(2-Ethoxyethyl)-1H-pyrazolo[4,3-d]pyrimidines as potent phosphodiesterase 5 (PDE5) inhibitors

Michael B Tollefson; Brad A Acker; E J Jacobsen; Robert O Hughes; John K Walker; David N A Fox; Michael J Palmer; Sandra K Freeman; Ying Yu; Brian R Bond

doi:10.1016/j.bmcl.2010.03.111

1-(2-Ethoxyethyl)-1H-pyrazolo[4,3-d]pyrimidines as potent phosphodiesterase 5 (PDE5) inhibitors

Bioorg Med Chem Lett. 2010 May 15;20(10):3120-4. doi: 10.1016/j.bmcl.2010.03.111.

Authors

Michael B Tollefson¹, Brad A Acker, E J Jacobsen, Robert O Hughes, John K Walker, David N A Fox, Michael J Palmer, Sandra K Freeman, Ying Yu, Brian R Bond

Affiliation

¹ Pfizer Global Research and Development, Chesterfield, MO 63017, United States. michael.tollefson@yahoo.com

PMID: 20443228
DOI: 10.1016/j.bmcl.2010.03.111

Abstract

1H-Pyrazolo[4,3-d]pyrimidines are a class of potent and selective second generation phosphodiesterase 5 (PDE5) inhibitors. This work explores the potency, selectivity and efficacy of 1-(2-ethoxyethyl)-1H-pyrazolo[4,5-d]pyrimidines as PDE5 inhibitors resulting in the advancement of a clinical candidate.

MeSH terms

Animals
Cyclic Nucleotide Phosphodiesterases, Type 5 / metabolism
Dogs
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacokinetics
Humans
Microsomes, Liver / metabolism
Phosphodiesterase 5 Inhibitors*
Pyrimidines / chemical synthesis
Pyrimidines / chemistry*
Pyrimidines / pharmacokinetics
Structure-Activity Relationship

Substances

Enzyme Inhibitors
Phosphodiesterase 5 Inhibitors
Pyrimidines
Cyclic Nucleotide Phosphodiesterases, Type 5