Minimization of drug-drug interaction risk and candidate selection in a natural product-based class of gamma-secretase modulators.
Bioorg Med Chem Lett
; 25(7): 1621-6, 2015 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-25708617
ABSTRACT
Early lead compounds in this gamma secretase modulator series were found to potently inhibit CYP3A4 and other human CYP isoforms increasing their risk of causing drug-drug-interactions (DDIs). Using structure-activity relationships and CYP3A4 structural information, analogs were developed that minimized this DDI potential. Three of these new analogs were further characterized by rat PK, rat PK/PD and rat exploratory toxicity studies resulting in selection of SPI-1865 (14) as a preclinical development candidate.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Esteroides
/
Azetidinas
/
Produtos Biológicos
/
Citocromo P-450 CYP3A
Tipo de estudo:
Etiology_studies
/
Risk_factors_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2015
Tipo de documento:
Article