Prolonged stability by cyclization: Macrocyclic phosphino dipeptide isostere inhibitors of beta-secretase (BACE1).
Bioorg Med Chem Lett
; 19(15): 4427-31, 2009 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-19523824
ABSTRACT
Cyclization of recently reported linear phosphino dipeptide isostere inhibitors of BACE1 via side chain olefin metathesis yielded macrocyclic BACE1 inhibitors. The most potent compound II-P1 (IC(50) of 47nM) and the corresponding linear analog I were tested for serum stability. The approach led to three times prolonged half life serum stability of 44min for the macrocyclic inhibitor II-P1 compared to the linear compound I.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Química Farmacêutica
/
Ácido Aspártico Endopeptidases
/
Secretases da Proteína Precursora do Amiloide
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article