Mitigation of cardiovascular toxicity in a series of CSF-1R inhibitors, and the identification of AZD7507.
Bioorg Med Chem Lett
; 23(16): 4591-6, 2013 Aug 15.
Article
em En
| MEDLINE
| ID: mdl-23842474
ABSTRACT
The potent and selective 3-amido-4-anilinoquinoline CSF-1R inhibitor AZ683 suffered from cardiovascular liabilities, which were linked to the off-target activities of the compound and ion channel activity in particular. Less basic and less lipophilic examples from both the quinoline and cinnoline series demonstrated cleaner secondary pharmacology profiles. Cinnoline 31 retained the required potency and oral PK profile, and was progressed through the safety screening cascade to be nominated into development as AZD7507.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Sistema Cardiovascular
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Receptor de Fator Estimulador de Colônias de Macrófagos
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Inibidores Enzimáticos
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Aminoquinolinas
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Compostos Heterocíclicos com 2 Anéis
/
Compostos de Anilina
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2013
Tipo de documento:
Article