Identification of pyridazino[4,5-b]indolizines as selective PDE4B inhibitors

Andrew F Donnell; Paul J Dollings; John A Butera; Arlene J Dietrich; Kerri K Lipinski; Afshin Ghavami; Warren D Hirst

doi:10.1016/j.bmcl.2010.02.044

Identification of pyridazino[4,5-b]indolizines as selective PDE4B inhibitors

Bioorg Med Chem Lett. 2010 Apr 1;20(7):2163-7. doi: 10.1016/j.bmcl.2010.02.044. Epub 2010 Feb 13.

Authors

Andrew F Donnell¹, Paul J Dollings, John A Butera, Arlene J Dietrich, Kerri K Lipinski, Afshin Ghavami, Warren D Hirst

Affiliation

¹ Worldwide Medicinal Chemistry, Pfizer Global Research and Development, CN 8000, Princeton, NJ 08543, USA. donnela@wyeth.com

PMID: 20202838
DOI: 10.1016/j.bmcl.2010.02.044

Abstract

Substituted pyridazino[4,5-b]indolizines were identified as potent and selective PDE4B inhibitors. We describe the structure-activity relationships generated around an HTS hit that led to a series of compounds with low nanomolar affinity for PDE4B and high selectivity over the PDE4D subtype.

MeSH terms

Cyclic Nucleotide Phosphodiesterases, Type 4 / metabolism*
Humans
Indolizines / chemistry*
Indolizines / pharmacology*
Phosphodiesterase 4 Inhibitors*
Phosphodiesterase Inhibitors / chemistry*
Phosphodiesterase Inhibitors / pharmacology*
Structure-Activity Relationship

Substances

Indolizines
Phosphodiesterase 4 Inhibitors
Phosphodiesterase Inhibitors
Cyclic Nucleotide Phosphodiesterases, Type 4