Synthesis and biological activity of 5-aryl-4-(4-(5-methyl-1H-imidazol-4-yl)piperidin-1-yl)pyrimidine analogs as potent, highly selective, and orally bioavailable NHE-1 inhibitors.
Bioorg Med Chem Lett
; 16(18): 4796-9, 2006 Sep 15.
Article
em En
| MEDLINE
| ID: mdl-16870436
ABSTRACT
A series of potent inhibitors of the sodium hydrogen exchanger-1 (NHE-1) is described. Structure-activity relationships identified the 3-methyl-4-fluoro analog 9t as a highly potent (IC50 = 0.0065 microM) and selective (NHE-2/NHE-1=1400) non-acylguanidine NHE-1 inhibitor. Pharmacokinetic studies showed that compound 9t has an oral bioavailability of 52% and a plasma half life of 1.5 h in rats. Because of its promising potency, selectivity, and a good pharmacokinetic profile, compound 9t was selected for further studies.
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Base de dados:
MEDLINE
Assunto principal:
Piperidinas
/
Pirimidinas
/
Trocadores de Sódio-Hidrogênio
Limite:
Animals
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article