Novel N-indolylmethyl substituted olanzapine derivatives: their design, synthesis and evaluation as PDE4B inhibitors.
Org Biomol Chem
; 11(13): 2075-9, 2013 Apr 07.
Article
em En
| MEDLINE
| ID: mdl-23436140
ABSTRACT
A new strategy for converting antipsychotic drug olanzapine into PDE4 inhibitors is described via the design and Pd/C mediated synthesis of novel N-indolylmethyl olanzapine derivatives. One compound showed good inhibition (IC50 1.1 µM) and >10 fold selectivity towards PDE4B over D that was supported by docking studies. This compound also showed significant inhibition of TNF-α and no major toxicities in cell lines and a zebrafish embryo model except the teratogenic effects to be re-assessed in rodents.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antipsicóticos
/
Benzodiazepinas
/
Desenho de Fármacos
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Nucleotídeo Cíclico Fosfodiesterase do Tipo 4
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Inibidores da Fosfodiesterase 4
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Org Biomol Chem
Ano de publicação:
2013
Tipo de documento:
Article