7-Oxopyrrolopyridine-derived DPP4 inhibitors-mitigation of CYP and hERG liabilities via introduction of polar functionalities in the active site.
Bioorg Med Chem Lett
; 21(22): 6646-51, 2011 Nov 15.
Article
em En
| MEDLINE
| ID: mdl-21996520
ABSTRACT
Design, synthesis, and SAR of 7-oxopyrrolopyridine-derived DPP4 inhibitors are described. The preferred stereochemistry of these atropisomeric biaryl analogs has been identified as Sa. Compound (+)-3t, with a K(i) against DPP4, DPP8, and DPP9 of 0.37 nM, 2.2, and 5.7 µM, respectively, showed a significant improvement in insulin response after single doses of 3 and 10 µmol/kg in ob/ob mice.
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Base de dados:
MEDLINE
Assunto principal:
Piridinas
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Dipeptidil Peptidase 4
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Citocromo P-450 CYP3A
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Canais de Potássio Éter-A-Go-Go
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Inibidores da Dipeptidil Peptidase IV
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article