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.
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MEDLINE
Assunto principal:
Esteroides
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Azetidinas
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Produtos Biológicos
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Citocromo P-450 CYP3A
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article