99984-70-0Relevant articles and documents
Anxiolytic- and antidepressant-like effects of new phenylpiperazine derivative LQFM005 and its hydroxylated metabolite in mice
Moreira, Lorrane Kelle da Silva,Silva, Rafaela Ribeiro,da Silva, Dayane Moreira,Mendes, Mirella Andrade Silva,de Brito, Adriane Ferreira,de Carvalho, Flávio Souza,Sanz, Germán,Rodrigues, Marcella Ferreira,da Silva, Artur Christian Garcia,Thomaz, Douglas Vieira,de Oliveira, Valéria,Vaz, Boniek Gontijo,Li?o, Luciano Morais,Valadares, Marize Campos,Gil, Eric de Souza,Costa, Elson Alves,No?l, Fran?ois,Menegatti, Ricardo
, (2021/09/28)
The current treatments available for anxiety and depression are only palliative. Full remission has remained elusive, characterizing unmet medical needs. In the scope of an academic drug discovery program, we describe here the design, synthesis, in vitro metabolism prediction and pharmacological characterization of a new piperazine compound, 1-(4-methoxyphenyl)?4-((1-phenyl-1H-pyrazol-4-yl)methyl)piperazine (LQFM005), and of its main putative metabolite, 4-(4-((4-(4-methoxyphenyl)piperazin-1-yl)methyl)? 1H-pyrazol-1-yl)phenol (LQFM235). The production of the metabolite was initially performed by in vitro biotransformation of LQFM005 using Aspergillus candidus and then by chemical synthesis. Oral administration of either 12 or 24 μmol/kg LQFM005 to mice did not affect spontaneous locomotor activity but increased the time spent in the center of the open field. Both LQFM005 and LQFM235 (24 μmol/kg) increased the time spent by the mice in the open arms of the elevated plus maze (EPM), a good indication of anxiolytic-like effect, and decreased the immobility time in the forced swimming test (FST), suggesting an antidepressant-like effect. The previous administration of WAY-100635 (a 5-HT1A antagonist) abolished the effects of LQFM005 in both EPM and FST. Binding experiments showed that LQFM005 and its metabolite bind to the 5-HT1A receptor with a moderate affinity (Ki around 5–9 μM). The two compounds are relatively safe, as indicated by cytotoxic assessment using the 3T3 fibroblast cell line and estimated LD50 around 600 mg/kg. In conclusion, oral administration of the newly synthesized phenylpiperazines produced anxiolytic- and antidepressant-like effects in behavioral tests, putatively in part through the activation of 5-HT1A receptors.
Chemoselective and regiospecific formylation of 1-phenyl-1H-pyrazoles through the duff reaction
De Oliveira,Mairink,Pazini,Liao,De Oliveira,Viegas Jr.,De Oliveira,Cunha,Oliveira,Paz Jr.,Eberlin,Menegatti, Ricardo
supporting information, p. 1633 - 1639 (2013/05/22)
The synthesis of formylated 1-phenyl-1H-pyrazole derivatives under the Duff reaction conditions is reported. Our results indicate that 1-phenyl-1H-pyrazole systems containing electron-withdrawing and electron-donating substituents at the phenyl moiety rea
