54605-72-0Relevant 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.
Unveiling Potent Photooxidation Behavior of Catalytic Photoreductants
Targos, Karina,Williams, Oliver P.,Wickens, Zachary K.
supporting information, p. 4125 - 4132 (2021/04/07)
We describe a photocatalytic system that reveals latent photooxidant behavior from one of the most reducing conventional photoredox catalysts, N-phenylphenothiazine (PTH). This aerobic photochemical reaction engages difficult to oxidize feedstocks, such as benzene, in C(sp2)-N coupling reactions through direct oxidation. Mechanistic studies are consistent with activation of PTH via photooxidation and with Lewis acid cocatalysts scavenging inhibitors inextricably formed in this process.
Design, synthesis and pharmacological assessment of new pyrazole compounds
Costa, Elson A.,Florentino, Iziara F.,Li?o, Luciano M.,Menegatti, Ricardo,Oliveria, Jordana C.,Pazini, Francine,Sanz, Germán,Silva, Daiany P. B.,Valadares, Marize C.,Vaz, Boniek G.,Verli, Hugo,Villavicencio, Bianca,da Silva, Lidya C.,de Carvalho, Flávio S.,dos Santos, Fernanda Cristina Alcantara,dos Santos, Thaís Rosa Marques
, p. 915 - 928 (2020/07/21)
Aims: This study investigated the antinociceptive and anti-inflammatory effects of new pyrazole compounds LQFM011(5), LQFM043(6) and LQFM044(7) as well as the mechanisms of action and acute in vitro toxicity. Main methods: The antinociceptive activity was evaluated using the acetic acid-induced abdominal writhing test, formalin-induced pain test and the Randall–Selitto test. The anti-inflammatory activity was evaluated using models of paw oedema and pleurisy induced by carrageenan; cell migration, the levels of tumour necrosis factor α (TNF-α) and myeloperoxidase (MPO) enzyme activity were evaluated. In addition, the ability to inhibit phospholipase A2 (PLA2) in vitro and docking in PLA2 were used. Acute oral systemic toxicity in mice was evaluated through the neutral red uptake assay. Key findings: The synthesised compounds (5–7), delivered via gavage (p.o.) at 70, 140 or 280 μmol/kg, decreased the number of writhings induced by acetic acid; the three compounds (280 μmol/kg p.o.) reduced the paw licking time in the first and second phase of the formalin test and decreased the nociceptive threshold variation in the Randall–Selitto test. Furthermore, this dose reduced oedema formation, leucocyte migration (specifically through reduction in polymorphonuclear cell movement) and increased mononuclear cells. MPO activity and the levels of pro-inflammatory cytokines TNF-α were decreased. Evaluation of PLA2 inhibition via the docking simulation revealed more interactions of LQFM043R(6) and LQFM044(7), data that corroborated the half-maximal inhibitory concentration (IC50) of PLA2 inhibition in vitro. Therefore, LQFM011(5), LQFM043(6) and LQFM044(7) were classified with the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) as category 4.
