Studies directed toward the design of orally active renin inhibitors. 1. Some factors influencing the absorption of small peptides.
J Med Chem
; 36(4): 449-59, 1993 Feb 19.
Article
em En
| MEDLINE
| ID: mdl-8474101
ABSTRACT
A systematic evaluation of structure-absorption relationships using a high throughput intraduodenal rat screening model has led to the delineation of a set of structural parameters that appear to govern bioavailability in a series of peptide-based renin inhibitors. Optimum structures, exemplified by 25 and 41, incorporated a single, solubilizing substituent at the C- or N-terminus combined with a lipophilic P2-site residue. Both inhibitors gave unprecedented plasma drug levels upon intraduodenal administration to monkeys, and the calculated bioavailability for 41 (14 +/- 4%) is the highest reported for any peptidic renin inhibitor.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oxazóis
/
Peptídeos
/
Piperazinas
/
Desenho de Fármacos
/
Renina
/
Dipeptídeos
/
Absorção Intestinal
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Med Chem
Assunto da revista:
QUIMICA
Ano de publicação:
1993
Tipo de documento:
Article