Synthetic studies of five-membered heteroaromatic derivatives as potassium-competitive acid blockers (P-CABs).
Bioorg Med Chem Lett
; 25(10): 2037-40, 2015.
Article
en En
| MEDLINE
| ID: mdl-25891103
ABSTRACT
On the basis of a series of novel and potent potassium-competitive acid blockers represented by 1-sulfonylpyrrole derivative 7, we prepared several five-membered heterocyclic analogues (8) and evaluated their H(+),K(+)-ATPase activities in vitro. We also assessed the role of the methylaminomethyl side chain by comparison with methylamino and ethylamino derivatives. We observed that the five-membered core ring and its orientation affect inhibitory activity and that the methylaminomethyl moiety is the best side chain. On the basis of potency and ligand-lipophilicity efficiency, compound 7 remains the most drug-like of the compounds studied to date. This study revealed the factors necessary for potent H(+),K(+)-ATPase inhibition, such as differences in electron density, the properties of the lone pair at each apical position of the heteroaromatic ring, and the geometry of the substituents.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
ATPasa Intercambiadora de Hidrógeno-Potásio
/
Compuestos Heterocíclicos
/
Hidrocarburos Aromáticos
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2015
Tipo del documento:
Article