Structure-activity relationships for inhibition of inosine monophosphate dehydrogenase by nuclear variants of mycophenolic acid.
J Med Chem
; 39(21): 4181-96, 1996 Oct 11.
Article
em En
| MEDLINE
| ID: mdl-8863796
ABSTRACT
Structure-activity relationships in the region of the phthalide ring of the inosine monophosphate dehydrogenase inhibitor mycophenolic acid have been explored. Replacement of the lactone ring with other cyclic moieties resulted in loss of potency, especially for larger groups. Replacement of the ring by acyclic substituents also indicated a strong sensitivity to steric bulk. A phenolic hydroxyl group, with an adjacent hydrogen bond acceptor, was found to be essential for high potency. The aromatic methyl group was essential for activity; the methoxyl group could be replaced by ethyl to give a compound with 2-4 times the potency of mycophenolic acid in vitro and in vivo.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
IMP Desidrogenase
/
Ácido Micofenólico
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
J Med Chem
Assunto da revista:
QUIMICA
Ano de publicação:
1996
Tipo de documento:
Article
País de afiliação:
Estados Unidos