Discovery of triazolopyrimidine-based PDE8B inhibitors: Exceptionally ligand-efficient and lipophilic ligand-efficient compounds for the treatment of diabetes

…, KJ DiRico, KM Andrews, ML Millham, JC Parker…

Index: Deninno, Michael P.; Wright, Stephen W.; Etienne, John B.; Olson, Thanh V.; Rocke, Benjamin N.; Corbett, Jeffrey W.; Kung, Daniel W.; Dirico, Kenneth J.; Andrews, Kim M.; Millham, Michele L.; Parker, Janice C.; Esler, William; Van Volkenburg, Maria; Boyer, David D.; Houseknecht, Karen L.; Doran, Shawn D. Bioorganic and Medicinal Chemistry Letters, 2012 , vol. 22, # 17 p. 5721 - 5726

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Citation Number: 7

Abstract

PDE8B is a cAMP-specific isoform of the broader class of phosphodiesterases (PDEs). As no selective PDE8B inhibitors had been reported, a high throughput screen was run with the goal of identifying selective tools for exploring the potential therapeutic utility of PDE8B inhibition. Of the numerous hits, one was particularly attractive since it was amenable to rapid deconstruction leading to inhibitors with very high ligand efficiency (LE) and ...