Design and synthesis of N-substituted indazole-3-carboxamides as poly(ADP-ribose)polymerase-1 (PARP-1) inhibitors().
Chem Biol Drug Des
; 79(4): 488-96, 2012 Apr.
Article
em En
| MEDLINE
| ID: mdl-22177599
ABSTRACT
A group of novel N-1-substituted indazole-3-carboxamide derivatives were synthesized and evaluated as inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1). A structure-based design strategy was applied to a weakly active unsubstituted 1H-indazole-3-carboxamide 2, by introducing a three carbon linker between 1H-indazole-3-carboxamide and different heterocycles, and led to compounds 4 [1-(3-(piperidine-1-yl)propyl)-1H-indazole-3-carboxamide, IC(50) =36µm] and 5 [1-(3-(2,3-dioxoindolin-1-yl)propyl)-1H-indazole-3-carboxamide, IC(50) = 6.8µm]. Compound 5 was evaluated in rats for its protective action against diabetes induced by a treatment with streptozotocin, a known diabetogenic agent. In addition to preserving the ability of the pancreas to secrete insulin, compound 5 was also able to attenuate the ensuing hyperglycemic response to a significant extent.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Diabetes Mellitus Experimental
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Inibidores de Poli(ADP-Ribose) Polimerases
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Hipoglicemiantes
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Indazóis
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article