1.
Bioorg Med Chem Lett
; 17(1): 205-7, 2007 Jan 01.
Artigo
em Inglês
| MEDLINE
| ID: mdl-17046254
RESUMO
The development of a novel series of tetrahydroquinoline-derived gamma-secretase inhibitors for the potential treatment of Alzheimer's disease is described.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Inibidores de Proteases/química , Quinolinas/química , Sulfonamidas/química , Humanos , Inibidores de Proteases/síntese química , Quinolinas/síntese química , Relação Estrutura-Atividade , Sulfonamidas/síntese química
2.
Bioorg Med Chem Lett
; 17(1): 57-62, 2007 Jan 01.
Artigo
em Inglês
| MEDLINE
| ID: mdl-17055268
RESUMO
A novel piperidine series of gamma-secretase inhibitors, potentially useful for the treatment of Alzheimer's disease, is disclosed. SAR investigation revealed the requirement for cis-stereochemistry of the substituents attached to the core, which resulted in the chair-like diaxial conformation of the piperidine ring. The series was optimized to provide inhibitors with IC(50)'s in the single-digit nanomolar range. Absolute stereochemistry of the active enantiomer was assigned.