Optimization of 2-piperidin-4-yl-acetamides as melanin-concentrating hormone receptor 1 (MCH-R1) antagonists: Designing out hERG inhibition

…, DGA Morgan, T Inghardt, F Giordanetto

Index: Berglund, Susanne; Egner, Bryan J.; Graden, Henrik; Graden, Joakim; Morgan, David G.A.; Inghardt, Tord; Giordanetto, Fabrizio Bioorganic and Medicinal Chemistry Letters, 2009 , vol. 19, # 15 p. 4268 - 4273

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Citation Number: 12

Abstract

Herein, we disclose the discovery and optimization of 2-piperidin-4-yl-acetamide derivatives as MCH-R1 antagonists. Structural investigation of piperidin-4-yl-amide and piperidin-4-yl- ureas identified 2-piperidin-4-yl-acetamide-based MCH-R1 antagonists with outstanding in vivo efficacy but flawed with high affinity towards the hERG potassium channel. While existing hERG SAR information was employed to discover highly potent MCH-R1 ...