1.
Bioorg Med Chem Lett
; 17(14): 3910-5, 2007 Jul 15.
Artigo
em Inglês
| MEDLINE
| ID: mdl-17502143
RESUMO
We report the synthesis of benzoazepine-derived cyclic malonamides (2) and aminoamides (3) as gamma-secretase inhibitors for the potential treatment of Alzheimer's disease. The in vitro structure-activity relationships of 2 and 3 along with dog pharmacokinetic results are described.
Assuntos
Amidas/farmacologia , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Azepinas/química , Azepinas/farmacologia , Azepinas/síntese química , Ciclização , Modelos Moleculares , Relação Estrutura-Atividade
2.
Bioorg Med Chem Lett
; 16(9): 2357-63, 2006 May 01.
Artigo
em Inglês
| MEDLINE
| ID: mdl-16473009
RESUMO
The synthesis, evaluation, and structure-activity relationships of a series of succinoyl lactam inhibitors of the Alzheimer's disease gamma-secretase are described. Beginning with a screening hit with broad proteinase activity, optimization provided compounds with both high selectivity for inhibition of gamma-secretase and high potency in cellular assays of A beta reduction. The SAR and early in vivo properties of this series of inhibitors will be presented.