Discovery of disubstituted cyclohexanes as a new class of CC chemokine receptor 2 antagonists.
J Med Chem
; 51(4): 721-4, 2008 Feb 28.
Article
em En
| MEDLINE
| ID: mdl-18232650
ABSTRACT
We describe the design, synthesis, and evaluation of novel disubstituted cyclohexanes as potent CCR2 antagonists. Exploratory SAR studies led to the cis-disubstituted derivative 22, which displayed excellent binding affinity for CCR2 (binding IC50 = 5.1 nM) and potent functional antagonism (calcium flux IC50 = 18 nM and chemotaxis IC 50 = 1 nM). Site-directed mutagenesis studies with 22 suggest the compound is binding near the key receptor residue Glu291, however, 22 is not reliant on Glu291 for its binding affinity.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Cicloexanos
/
Receptores CCR2
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article