RESUMEN
The design, synthesis and structure-activity relationships of a novel series of 3,4-disubstituted pyrrolidine acid analogs as PPAR ligands is outlined. In both the 1,3- and 1,4-oxybenzyl pyrrolidine acid series, the preferred stereochemistry was shown to be the cis-3R,4S isomer, as exemplified by the potent dual PPARα/γ agonists 3k and 4i. The N-4-trifluoromethyl-pyrimidinyl pyrrolidine acid analog 4i was efficacious in lowering fasting glucose and triglyceride levels in diabetic db/db mice.
Asunto(s)
Hipoglucemiantes/síntesis química , PPAR alfa/agonistas , PPAR gamma/agonistas , Pirrolidinas/química , Animales , Glucemia/análisis , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diseño de Fármacos , Femenino , Hipoglucemiantes/química , Hipoglucemiantes/uso terapéutico , Ligandos , Ratones , Ratones Obesos , PPAR alfa/metabolismo , PPAR gamma/metabolismo , Pirrolidinas/síntesis química , Pirrolidinas/uso terapéutico , Estereoisomerismo , Relación Estructura-Actividad , Triglicéridos/sangreRESUMEN
In neurovascular surgery, and in particular surgery for arteriovenous malformations (AVMs), the surgeon maps pre-operative images to the patient on the operating table to aid in vessel localization and resection. This type of spatial mapping is not trivial, is time consuming, and may be prone to error. Using augmented reality (AR) we can register the microscope/camera image of the patient to pre-operative data in order to help the surgeon better understand the topology and locations of vessels that lie below the visible surface of the cortex. In this work we describe a prototype system, developed using open source software and built with off-the-shelf hardware, for AR visualization for AVM neurosurgery. Furthermore, we consider two visualization techniques, colour-coding and chromadepth, to enhance the depth perception of vessels.