RESUMO
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.
Assuntos
Clorobenzenos/síntese química , Dioxóis/síntese química , Dioxóis/farmacologia , Hidrazinas/química , Propionatos/síntese química , Pirazóis/química , Pirazóis/farmacologia , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Clorobenzenos/química , Dioxóis/química , Hidrólise , Cetonas/química , Estrutura Molecular , Propionatos/química , Pirazóis/síntese química , EstereoisomerismoRESUMO
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.