Optimization of 2-piperidin-4-yl-acetamides as melanin-concentrating hormone receptor 1 (MCH-R1) antagonists: Designing out hERG inhibition.
Bioorg Med Chem Lett
; 19(15): 4268-73, 2009 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-19500979
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 antagonists with minimized hERG inhibition, additional hurdles prevented their subsequent clinical exploration.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Piperidinas
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Receptores do Hormônio Hipofisário
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Química Farmacêutica
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Canais de Potássio Éter-A-Go-Go
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Acetamidas
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article