Anion-triggered substituent-dependent conformational switching of salicylanilides. New hints for understanding the inhibitory mechanism of salicylanilides.
J Org Chem
; 72(26): 9947-53, 2007 Dec 21.
Article
em En
| MEDLINE
| ID: mdl-18020364
ABSTRACT
A series of salicylanilides (1a-h) bearing varied substituents at the 3'- or 4'-position of the anilino moiety (substituent = p-OCH3, p-CH3, m-CH3, H, p-Cl, m-Cl, p-CO2CH3, and p-CN) were synthesized. In acetonitrile all of the substituted salicylanilides 1a-h predominantly adopt the "closed-ring" conformation facilitated by a strong intramolecular OH...O=C hydrogen bond. In the presence of H2PO4-, the conformation of 1a-h was found to be modulated by the substituent. With our proposed proton-transfer fluorescence probing method, we were able to show that the conformation of 1a-f bearing a not highly electron-withdrawing substituent was switched to the "open-ring" form by H2PO4-, whereas 1h bearing a highly electron-withdrawing substituent, p-CN, remained in the "closed-ring" conformation. The significance of these findings for understanding, from a molecular structural point of view, the mechanism of salicylanilide-based inhibitors for inhibiting the protein tyrosine kinase epidermal growth factor receptor was discussed.
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Base de dados:
MEDLINE
Assunto principal:
Salicilanilidas
/
Inibidores de Proteínas Quinases
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article