Synthesis, anticancer activity, and SAR analyses of compounds containing the 5:7-fused 4,6,8-triaminoimidazo[4,5-e][1,3]diazepine ring system.
Bioorg Med Chem
; 24(12): 2595-602, 2016 06 15.
Article
em En
| MEDLINE
| ID: mdl-27134120
ABSTRACT
Described herein are our limited structure-activity relationship (SAR) studies on a 57-fused heterocycle (1), containing the 4,6,8-triaminoimidazo[4,5-e][1,3]diazepine ring system, whose synthesis and potent broad-spectrum anticancer activity we reported a few years ago. Our SAR efforts in this study are mainly focused on judicial attachment of substituents at N-1 and N(6)-positions of the heterocyclic ring. Our results suggest that there is some subtle correlation between the substituents attached at the N-1 position and those attached at the N(6)-position of the heterocycle. It is likely that there is a common hydrophobic binding pocket on the target protein that is occupied by the substituents attached at the N-1 and N(6)-positions of the heterocyclic ligand. This pocket appears to be large enough to hold either a C-18 alkyl chain of N(6) and no attachment at N-1, or a combined C-10 at N(6) and a CH2Ph at N-1. Any alkyl chain shorter or longer than C-10 at N(6) with a CH2Ph attached at N-1, would result in decrease of biological activity.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Azepinas
/
Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2016
Tipo de documento:
Article