Category: 17355-75-8

Discovery of 1,5-Diphenylpyrazole-3-Carboxamide Derivatives as Potent, Reversible, and Selective Monoacylglycerol Lipase (MAGL) Inhibitors was written by Aghazadeh-Tabrizi, Mojgan;Baraldi, Pier Giovanni;Baraldi, Stefania;Ruggiero, Emanuela;De Stefano, Lucia;Rizzolio, Flavio;Di Cesare Mannelli, Lorenzo;Ghelardini, Carla;Chicca, Andrea;Lapillo, Margherita;Gertsch, Jurg;Manera, Clementina;Macchia, Marco;Martinelli, Adriano;Granchi, Carlotta;Minutolo, Filippo;Tuccinardi, Tiziano. And the article was included in Journal of Medicinal Chemistry in 2018.COA of Formula: C18H16N2O2 The following contents are mentioned in the article:

Monoacylglycerol lipase (MAGL) is a serine hydrolase that plays an important role in the degradation of the endocannabinoid neurotransmitter 2-arachidonoylglycerol, which is implicated in many physiol. processes. Beyond the possible utilization of MAGL inhibitors as anti-inflammatory, antinociceptive, and anticancer agents, their application has encountered obstacles due to the unwanted effects caused by the irreversible inhibition of this enzyme. The possible application of reversible MAGL inhibitors has only recently been explored, mainly due to the deficiency of known compounds possessing efficient reversible inhibitory activities. The authors report a new series of reversible MAGL inhibitors. Among them, compound 26 ((4-benzylpiperidin-1-yl)(5-(4-hydroxyphenyl)-1-(3-methylbenzyl)-1H-pyrazol-3-yl)methanone) showed to be a potent MAGL inhibitor (IC₅₀ = 0.51 μM, K_i = 412 nM) with a good selectivity vs. fatty acid amide hydrolase (FAAH), α/β-hydrolase domain-containing 6 (ABHD6), and 12 (ABHD12). Interestingly, this compound also possesses antiproliferative activities against two different cancer cell lines and relieves the neuropathic hypersensitivity induced in vivo by oxaliplatin. This study involved multiple reactions and reactants, such as Ethyl 1,5-diphenyl-1H-pyrazole-3-carboxylate (cas: 17355-75-8COA of Formula: C18H16N2O2).

Ethyl 1,5-diphenyl-1H-pyrazole-3-carboxylate (cas: 17355-75-8) belongs to pyrazole derivatives. Pyrazoles, a five-membered heterocycle containing two adjacent nitrogen atoms, are the core structures found in a number of molecules that possess a wide range of pharmaceutical and agricultural activities. The presence of both electronegative nitrogen atoms in the pyrazole ring reduces the electron density of the C3- and C5-positions leaving electron density of C4-position unaltered. Thus the C4-position is vulnerable to electrophilic attack. The C3 electrophilic-position may undergo deprotonation in the presence of a strong base leading to ring opening.COA of Formula: C18H16N2O2

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Transformation of 3-isoxazolecarboxylic acids into pyrazole derivatives. IV was written by Cusmano, Sigismondo. And the article was included in Gazzetta Chimica Italiana in 1940.Safety of Ethyl 1,5-diphenyl-1H-pyrazole-3-carboxylate The following contents are mentioned in the article:

cf. C. A. 34, 7903.8. The transformation of 3-isoxazolecarboxylic acids into pyrazolonimines by fusion with PhNHNH₂ may proceed by decarboxylation followed by ring closure of the resulting cyano ketone phenylhydrazone. To test this hypothesis the fusion was repeated in the presence of Natur Kupfer C (I) (or ordinary reduced Cu) so that, at the lower decarboxylation temperatures it might be possible to isolate the phenylhydrazone prior to ring closure and so shed some light on the mechanism of the reaction. A mixture of 1 g. of 5-phenyl-3-isoxazolecarboxylic acid (II), 1 g. I and 1 g. PhNHNH₂ in 20 cc. alc. was boiled for a few min. over a free flame, filtered, alkalinized with Na₂CO₃, extracted free from PhNHNH₂ with ether, acidified with dilute H₂SO₄, and extracted with ether. The residue from the evaporated extract gave 1,5-diphenyl-3-pyrazolecarboxylic acid (III), m. 185° (Et ester, m. 98°), decarboxylated by fusion to give 1,5-diphenylpyrazole, m. 55°, and identical with the known acid prepared by the action of PhNHNH₂ on BzCH₂COCO₂H. A similar transformation of 5-methyl-3-isoxazolecarboxylic acid (IV) gave 1-phenyl-5-methyl-3-pyrazolecarboxylic acid, m. 136° (Me ester, m. 55°), decarboxylated to 1-phenyl-5-methylpyrazole, transformed into the known picrate, m. 98°. In these transformations alc. can be replaced by other solvents. In the absence of I or in the presence of PhNH₂ instead of PhNHNH₂ the isoxazolecarboxylic acid is recovered unchanged. This study involved multiple reactions and reactants, such as Ethyl 1,5-diphenyl-1H-pyrazole-3-carboxylate (cas: 17355-75-8Safety of Ethyl 1,5-diphenyl-1H-pyrazole-3-carboxylate).

Ethyl 1,5-diphenyl-1H-pyrazole-3-carboxylate (cas: 17355-75-8) belongs to pyrazole derivatives. The strategies for the synthesis of pyrazoles generally can be applied for the construction of indazoles. Protonation of pyrazole in strong acid leads to pyrazolium cations, which undergo electrophilic substitution preferentially at C3 rather than C4. The pyrazole anion is not reactive toward nucleophiles but is mostly reactive to electrophiles.Safety of Ethyl 1,5-diphenyl-1H-pyrazole-3-carboxylate

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics