The discovery and synthesis of highly potent subtype selective phosphodiesterase 4D inhibitors

✍ Scribed by Renee Aspiotis; Denis Deschênes; Daniel Dubé; Yves Girard; Zheng Huang; France Laliberté; Susana Liu; Robert Papp; Donald W. Nicholson; Robert N. Young

• Book ID: 104004677
• Publisher: Elsevier Science
• Year: 2010
• Tongue: English
• Weight: 344 KB
• Volume: 20
• Category: Article
• ISSN: 0960-894X
• DOI: 10.1016/j.bmcl.2010.07.076

✦ Synopsis

The SAR study of a series of 6-aryloxymethyl-8-aryl substituted quinolines is described. Optimization of the series led to the discovery of compound 26b, a highly potent (IC50=0.6 nM) and selective PDE4D inhibitor with a 75-fold selectivity over the A, B, and C subtypes and over 18,000-fold selectivity against other PDE family members. Rat pharmacokinetics and tissue distribution are also summarized.