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

Bioorganic & Medicinal Chemistry Letters（2010）

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摘要

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.

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关键词

Selective phosphodiesterase inhibitors,Pyridazino[4,5-b]indolizines,Hit-to-lead

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