The identification of 4,7-disubstituted naphthoic acid derivatives as UDP-competitive antagonists of P2Y14.
Bioorg Med Chem Lett
; 21(10): 2836-9, 2011 May 15.
Article
en En
| MEDLINE
| ID: mdl-21507640
ABSTRACT
A weak, UDP-competitive antagonist of the pyrimidinergic receptor P2RY(14) with a naphthoic acid core was identified through high-throughput screening. Optimization provided compounds with improved potency but poor pharmacokinetics. Acylglucuronidation was determined to be the major route of metabolism. Increasing the electron-withdrawing nature of the substituents markedly reduced glucuronidation and improved the pharmacokinetic profile. Additional optimization led to the identification of compound 38 which is an 8 nM UDP-competitive antagonist of P2Y(14) with a good pharmacokinetic profile.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Uridina Difosfato
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Ácidos Carboxílicos
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Receptores Purinérgicos P2
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Antagonistas del Receptor Purinérgico P2
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Naftalenos
Tipo de estudio:
Diagnostic_studies
Límite:
Animals
Idioma:
En
Año:
2011
Tipo del documento:
Article