5 research outputs found
Capillary microsampling in mice: effective way to move from sparse sampling to serial sampling in pharmacokinetics profiling
No full textEvaluation of separate role of intestine and liver in first pass metabolism of budesonide in rat
No full textDiscovery of Potent and Selective A<sub>2A</sub> Antagonists with Efficacy in Animal Models of Parkinson’s Disease and Depression
No full textAdenosine A<sub>2A</sub> receptor
(A<sub>2A</sub>AdoR) antagonism is a nondopaminergic approach to Parkinson’s
disease treatment that is under development. Earlier we had reported
the therapeutic potential of 7-methoxy-4-morpholino-benzothiazole
derivatives as A<sub>2A</sub>AdoR antagonists. We herein described
a novel series of [1,2,4]triazolo[5,1-<i>f</i>]purin-2-one
derivatives that displays functional antagonism of the A<sub>2A</sub> receptor with a high degree of selectivity over A<sub>1</sub>, A<sub>2B</sub>, and A<sub>3</sub> receptors. Compounds from this new scaffold
resulted in the discovery of highly potent, selective, stable, and
moderate brain penetrating compound <b>33</b>. Compound <b>33</b> endowed with satisfactory <i>in vitro</i> and <i>in vivo</i> pharmacokinetics properties. Compound <b>33</b> demonstrated robust oral efficacies in two commonly used models
of Parkinson’s disease (haloperidol-induced catalepsy and 6-OHDA
lesioned rat models) and depression (TST and FST mice models)
