Investigation of the pyrazinones as PDE5 inhibitors: evaluation of regioisomeric projections into the solvent region

Robert O Hughes; Todd Maddux; D Joseph Rogier; Sharon Lu; John K Walker; E Jon Jacobsen; Jeanne M Rumsey; Yi Zheng; Alan Macinnes; Brian R Bond; Seungil Han

doi:10.1016/j.bmcl.2011.08.106

Investigation of the pyrazinones as PDE5 inhibitors: evaluation of regioisomeric projections into the solvent region

Bioorg Med Chem Lett. 2011 Nov 1;21(21):6348-52. doi: 10.1016/j.bmcl.2011.08.106. Epub 2011 Aug 31.

Authors

Robert O Hughes¹, Todd Maddux, D Joseph Rogier, Sharon Lu, John K Walker, E Jon Jacobsen, Jeanne M Rumsey, Yi Zheng, Alan Macinnes, Brian R Bond, Seungil Han

Affiliation

¹ Pfizer Global Research and Development, 700 Chesterfield Parkway West, St. Louis, MO 63017, USA. robowenhughes@gmail.com

PMID: 21955943
DOI: 10.1016/j.bmcl.2011.08.106

Abstract

We describe the design, synthesis and profiling of a novel series of PDE5 inhibitors. We take advantage of an alternate projection into the solvent region to identify compounds with excellent potency, selectivity and pharmacokinetic profiles.

MeSH terms

Crystallography, X-Ray
Inhibitory Concentration 50
Models, Molecular
Phosphodiesterase 5 Inhibitors / chemistry
Phosphodiesterase 5 Inhibitors / pharmacokinetics
Phosphodiesterase 5 Inhibitors / pharmacology*
Pyrazines / chemistry
Pyrazines / pharmacokinetics
Pyrazines / pharmacology*
Solvents / chemistry

Substances

Phosphodiesterase 5 Inhibitors
Pyrazines
Solvents