Core modification of substituted piperidines as novel inhibitors of HDM2-p53 protein-protein interaction.
Bioorg Med Chem Lett
; 24(8): 1983-6, 2014 Apr 15.
Article
em En
| MEDLINE
| ID: mdl-24656661
ABSTRACT
The discovery of 3,3-disubstituted piperidine 1 as novel p53-HDM2 inhibitors prompted us to implement subsequent SAR follow up directed towards piperidine core modifications. Conformational restrictions and further functionalization of the piperidine core were investigated as a strategy to gain additional interactions with HDM2. Substitutions at positions 4, 5 and 6 of the piperidine ring were explored. Although some substitutions were tolerated, no significant improvement in potency was observed compared to 1. Incorporation of an allyl side chain at position 2 provided a drastic improvement in binding potency.
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Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piperidinas
/
Proteína Supressora de Tumor p53
/
Proteínas Proto-Oncogênicas c-mdm2
Limite:
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article