RESUMEN
We describe a practical and scalable route to compound (Z)-1, a selective CCK1 receptor antagonist. Notable features of this concise route are (1) a regioselective construction of the pyrazole core through the reaction of an aryl hydrazine and an elaborated acetylenic ketone, (2) a Tf2O/pyridine mediated Z-selective dehydration of an α-hydroxyester, and (3) a stereoselective hydrolysis. The sequence is high-yielding and amenable for large-scale synthesis.
Asunto(s)
Clorobencenos/síntesis química , Dioxoles/síntesis química , Dioxoles/farmacología , Hidrazinas/química , Propionatos/síntesis química , Pirazoles/química , Pirazoles/farmacología , Receptores Acoplados a Proteínas G/antagonistas & inhibidores , Clorobencenos/química , Dioxoles/química , Hidrólisis , Cetonas/química , Estructura Molecular , Propionatos/química , Pirazoles/síntesis química , EstereoisomerismoRESUMEN
We have previously reported a novel class of tetrahydroindazoles that display potency against a variety of Gram-positive and Gram-negative bacteria, potentially via interaction with type II bacterial topoisomerases. Herein are reported SAR investigations of this new series. Several compounds possessing broad-spectrum potency were prepared. Further, these compounds exhibit activity against multidrug-resistant Gram-positive microorganisms equivalent to that against susceptible strains.