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Updated: May 19, 2026

Defining Substrate Specificities for Lipase and Phospholipase Candidates
Published on: November 23, 2016
Solubility-driven optimization of phosphodiesterase-4 inhibitors leading to a clinical candidate
Neil J Press1, Roger J Taylor, Joseph D Fullerton
1Novartis Institutes for Biomedical Research, Wimblehurst Road, Horsham, West Sussex RH12 5AB, U.K. neil.press@novartis.com
Abstract:
The solubility-driven optimization of a series of 1,7-napthyridine phosphodiesterase-4 inhibitors is described. Directed structural changes resulted in increased aqueous solubility, enabling superior pharmacokinetic properties with retention of PDE4 inhibition. A range of potent and orally bioavailable compounds with good in vivo efficacy in animal models of inflammation and reduced emetic potential compared to previously described drugs were synthesized. Compound 2d was taken forward as a clinical candidate for the treatment of COPD.
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