- Anxiolytic- and antidepressant-like effects of new phenylpiperazine derivative LQFM005 and its hydroxylated metabolite in mice
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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.
- 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
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- A pyrazolyl pyrimidine compound and use thereof
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The present invention discloses a pyrazolyl pyrilamine compound, the compound has a structure as shown in formula (I), and the substituent groups in the (I) are as defined in the specification. The pyrazolyl pyrilamine compound has good control effects on downy mildew of cucumber, puccinia polysra, wheat powdery mildew and other diseases, and is especially better in the control effect on the downy mildew of cucumber.
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Paragraph 0354; 0358-0360
(2017/08/30)
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- Chemoselective and regiospecific formylation of 1-phenyl-1H-pyrazoles through the duff reaction
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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
- De Oliveira,Mairink,Pazini,Liao,De Oliveira,Viegas Jr.,De Oliveira,Cunha,Oliveira,Paz Jr.,Eberlin,Menegatti, Ricardo
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supporting information
p. 1633 - 1639
(2013/05/22)
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- Synthesis and antileishmanial activity of new 1-aryl-1H-pyrazole-4- carboximidamides derivatives
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Chemotherapy for leishmaniasis, diseases caused by protozoa of the genus Leishmania, remains inefficient in several treatments. So there is a need to search for new drugs. In this work, we have synthesized 1-aryl-1H-pyrazole-4- carboximidamides derivatives and evaluated antileishmanial activities in vitro, as well as cytotoxic effects. Structure-activity relationship (SAR) studies were carried out with all the compounds of the series. Compound 2 showed an activity profile that can be improved through medicinal chemistry strategies.
- Dos Santos, Mauri?cio S.,Gomes, Adriana O.,Bernardino, Alice M. R.,De Souza, Marcos C.,Khan, Misbahul A.,De Brito, Monique A.,Castro, Helena C.,Abreu, Paula A.,Rodrigues, Carlos R.,De Le?o, Rosa M. M.,Leon, Leonor L.,Canto-Cavalheirr, Marilene M.
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experimental part
p. 352 - 358
(2011/10/04)
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