Renin inhibitors based on novel dipeptide analogues. Incorporation of the dehydrohydroxyethylene isostere at the scissile bond.
J Med Chem
; 30(11): 1978-83, 1987 Nov.
Article
en En
| MEDLINE
| ID: mdl-3312604
ABSTRACT
The design and synthesis of renin inhibitors that incorporate the novel dipeptide isostere (4S,5S)-5-amino-6-cyclohexyl-4-hydroxyhex-1-ene-2-carboxylic acid as a transition-state analogue are described. Titanium-promoted condensation of dilithiated N-alkylmethacrylamides with protected amino aldehydes results in efficient preparation of protected dipeptide analogues 7 and 8. Incorporation of 7 into the partial sequence of angiotensinogen affords potent in vitro inhibitors of human renin. Further chemical manipulation of the unsaturated amide moiety allows the study of structure-activity relationships in both the P1' and P2' sites. Details of the syntheses, stereochemical determinations, and in vitro renin inhibition are presented.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Renina
/
Dipéptidos
Límite:
Humans
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
1987
Tipo del documento:
Article