Design and synthesis of a new class of selective integrin alpha5beta1 antagonists.
J Med Chem
; 50(16): 3786-94, 2007 Aug 09.
Article
en En
| MEDLINE
| ID: mdl-17616113
ABSTRACT
Starting from the structure of integrin alphavbeta3 in a complex with a peptidic ligand plus SAR data on nonpeptidic ligands, we derived a new class of integrin alpha5beta1 antagonists (1). Several synthesis strategies were applied to evaluate the chemical space around the essential pharmacophore groups R1 to R3 to obtain highly active and selective pyrrolidine derivatives as integrin alpha5beta1 antagonists. Integrin selectivity was controlled by switching from a sulfonamide moiety to a mesitylene amide moiety for R3. This finding represents a general feature for modulating selectivity toward other related integrin receptors. On the basis of the encouraging results from various in vitro studies, the most active compounds were selected for further in vivo studies in animal models and preclinical development.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Piridinas
/
Pirrolidinas
/
Integrina alfa5beta1
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
2007
Tipo del documento:
Article
País de afiliación:
Alemania