Development of novel series of potent phosphodiesterase-4 (PDE4) inhibitors: SAR studies on substituted 4-(2,2-diarylethyl)pyridine-N-oxides

ORGN 472

Richard Frenette, Department of Medicinal Chemistry, Department of Medicinal Chemistry, Merck Frosst Centre for Therapeutic Research, P.O. Box 1005, Pointe Claire-Dorval, QC H9R 4P8, Canada
Intracellular modulation of cAMP levels by phosphodiesterase-4 (PDE4) inhibition represents a promising approach for the treatment of chronic inflammatory diseases such as asthma and chronic obstructive pulmonary disease (COPD). SAR studies performed to improve upon the lead compound CDP-840 with respect to PDE4 inhibitory potency, metabolism issues, and pharmacokinetic properties, culminated in the identification of the tertiary alcohol series. Compounds in the latter series showed to be potent and non-emetic PDE4 inhibitors but also possessed some ancillary cardiac activity. SAR studies to address this issue will also be discussed.
 

Technical Achievement in Organic Chemistry Awards
8:30 AM-11:25 AM, Wednesday, September 10, 2003 Sheraton New York -- Imperial Ballroom A, Oral

Division of Organic Chemistry
The 226th ACS National Meeting, New York, NY, September 7-11, 2003