RESUMEN
For over 30 years, rapamycin has generated a sustained and intense interest from the scientific community as a result of its exceptional pharmacological properties and challenging structural features. In addition to its well known therapeutic value as a potent immunosuppressive agent, rapamycin and its derivatives have recently gained prominence for the treatment of a wide variety of other human malignancies. Herein we disclose full details of our extensive investigation into the synthesis of rapamycin that culminated in a new and convergent preparation featuring a macro-etherification/catechol-templating strategy for construction of the macrocyclic core of this natural product.
Asunto(s)
Antineoplásicos/síntesis química , Productos Biológicos/síntesis química , Inmunosupresores/síntesis química , Sirolimus/síntesis química , Antineoplásicos/química , Antineoplásicos/farmacología , Productos Biológicos/química , Productos Biológicos/farmacología , Ciclización , Humanos , Inmunosupresores/química , Inmunosupresores/farmacología , Estructura Molecular , Sirolimus/química , Sirolimus/farmacologíaRESUMEN
The 4-amino-5-azaindole as an amidino-benzimidazole replacement is described. A series of potent and selective analogs were discovered and showed desirable ex vivo efficacy as measured by PT.
Asunto(s)
Factor VIIa/antagonistas & inhibidores , Indoles/síntesis química , Indoles/farmacología , Piridinas/síntesis química , Piridinas/farmacología , Factor VIIa/metabolismo , Indoles/química , Estructura Molecular , Piridinas/química , Relación Estructura-ActividadRESUMEN
The discovery and development of 5-azaindole factor VIIa inhibitors will be described.