1.
Bioorg Med Chem Lett
; 19(20): 5898-901, 2009 Oct 15.
Artículo
en Inglés
| MEDLINE
| ID: mdl-19733066
RESUMEN
A pharmacophore mapping approach, derived from previous experience of PIKK family enzymes, was used to identify a hit series of selective inhibitors of the mammalian target of rapamycin (mTOR). Subsequent refinement of the SAR around this hit series based on a tri-substituted triazine scaffold has led to the discovery of potent and selective inhibitors of mTOR.
Asunto(s)
Antineoplásicos/química , Morfolinas/química , Inhibidores de Proteínas Quinasas/química , Proteínas Quinasas/química , Pirimidinas/química , Triazinas/química , Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Línea Celular Tumoral , Humanos , Morfolinas/síntesis química , Morfolinas/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3 , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Quinasas/metabolismo , Pirimidinas/síntesis química , Pirimidinas/farmacología , Relación Estructura-Actividad , Serina-Treonina Quinasas TOR , Triazinas/síntesis química , Triazinas/farmacología
2.
Bioorg Med Chem Lett
; 18(14): 3942-5, 2008 Jul 15.
Artículo
en Inglés
| MEDLINE
| ID: mdl-18579376
RESUMEN
We have previously described poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors based on a substituted benzyl-phthalazinone scaffold. As an alternative chemical template, a novel series of alkoxybenzamides were developed with restricted conformation through intramolecular hydrogen bond formation; the compounds exhibit low nM enzyme and cellular activity as PARP-1 inhibitors.
