Boronic acid-containing aminopyridine- and aminopyrimidinecarboxamide CXCR1/2 antagonists: Optimization of aqueous solubility and oral bioavailability.
Bioorg Med Chem Lett
; 25(18): 3793-7, 2015 Sep 15.
Article
em En
| MEDLINE
| ID: mdl-26248802
ABSTRACT
The chemokine receptors CXCR1 and CXCR2 are important pharmaceutical targets due to their key roles in inflammatory diseases and cancer progression. We have previously identified 2-[5-(4-fluoro-phenylcarbamoyl)-pyridin-2-ylsulfanylmethyl]-phenylboronic acid (SX-517) and 6-(2-boronic acid-5-trifluoromethoxy-benzylsulfanyl)-N-(4-fluoro-phenyl)-nicotinamide (SX-576) as potent non-competitive boronic acid-containing CXCR1/2 antagonists. Herein we report the synthesis and evaluation of aminopyridine and aminopyrimidine analogs of SX-517 and SX-576, identifying (2-{(benzyl)[(5-boronic acid-2-pyridyl)methyl]amino}-5-pyrimidinyl)(4-fluorophenylamino)formaldehyde as a potent chemokine antagonist with improved aqueous solubility and oral bioavailability.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ácidos Borônicos
/
Niacinamida
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Receptores de Interleucina-8A
/
Receptores de Interleucina-8B
Limite:
Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article