Planejamento, síntese, biotransformação e avaliação farmacológica de novos candidatos a protótipos de fármacos antipsicóticos
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2010-08-30
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Universidade Federal de Goiás
Resumo
In the scope of a research program that aim the design, synthesis and
pharmacological evaluation of new lead-compounds, we will describe in this work the
design of new N-phenylpiperazines derivatives originally designed from clozapine
(27) and LASSBio 579 (40) that shows antagonist profile in dopaminergic receptors.
The compound 1-(4-nitrophenyl)-4-((1-phenyl-1H-pyrazol-4-yl)methyl)piperazine (45)
was submitted to in vitro pharmacology assay in brain rat tissues to evaluate the
inhibitory activity of D2 dopaminergic receptors and 5-HT2A and 5-HT1A serotonergic.
Besides synthetic and pharmacological works its realized biotransformation studies
using filamentous fungi and resulted lower number of metabolites than previous
studies of (40) biotransformation. Was observed a p-hydroxylated metabolites in the
aromatic ring A of 1-(4-methoxyphenyl)-4-((1-phenyl-1H-pyrazol-4-
yl)methyl)piperazine (44) and 1-(4-nitrophenyl)-4-((1-phenyl-1H-pyrazol-4-
yl)methyl)piperazine (45) were isolated and purified. We concluded that substitution
of the D ring contributes to protect from enzymatic metabolism, confirmed by lower
number of produced metabolites by biotransformation of the compound (40) . In
work, we concluded that the structural design and the synthetic methodology used
was validated through structural characterization, but the compounds not show
inhibitory profile of dopaminergics (D2) and serotonergics receptors (5-HT2A e 5-HT1A)
in front of the reference atypical antipsychotic.
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SILVA, Mirella Andrade. Planning, synthesis, biotransformation and pharmacological evaluation of new candidate prototype antipsychotic drugs. 2010. 105 f. Dissertação (Mestrado em Ciências da Saúde - Farmácia) - Universidade Federal de Goiás, Goiânia, 2010.