Synthesis of Some Novel Azo Derivatives of 3,5‐Dimethly‐1‐(2‐hydroxyethyl)pyrazole as Potent Analgesic Agents

Abstract

A series of 1-(2-hydroxyethyl)-3,5-dimethylpyrazolylazo derivatives, incorporating thiosemicarbazide 2a-c, 1,3,4-thiadiazole 3a-c, and 1,2,4-triazole-3-thione 4a-c were synthesized. The structure of these novel synthesized compounds 2a-c, 3a-c, and 4a-c was confirmed by spectral analysis. All these compounds were screened for their analgesic activity. Hot-plate and tail-immersion tests were used for the determination of the analgesic activity. Morphine, an analgesic through both spinal and supraspinal pathways, was used as a standard test drug. All compounds were administered at a dose of 100 mg/kg i.p. Among the compounds, 2-(butylamino)-5-[((1-(2-hydroxyethyl)-3,5-dimethylpyrazole-4-yl)azo)phenyl]-1,3,4-thiadiazole 3a and 4-[((1-(2-hydroxyethyl)-3,5-dimethylpyrazole-4-yl)azo)phenyl]-4-(2-phenethyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione 4c showed analgesic effects in both tests. Especially 4c exerted strong analgesia starting at 30 min after injection.

Regioselective synthesis and biological evaluation of some novel thiophene-containing heterocyclic scaffolds as potential chemotherapeutic agents

“…This downfield NH resonance in the isolated product from the studied reaction can be rationalized in terms of the presence of the thione group attached to the nitrogen atom linked to the thioamide proton and as a result this proton is deshielded by the thione group and appears around that chemical shift value. This assignment is in line with literature assignments, that predict this signal would appear typically in the range δH ~ 13.00-14.00 ppm by analogy with related heterocyclic thioamides [31][32][33][34][35][36][37]. On the contrary, the isomeric structure 7, if isolated, would be expected to display an upfield shift for the NH proton due to the absence of deshielding thione group.…”

Antimicrobial investigations on synthetic p-tolylazo derivatives of thienopyrimidinone based on an ortho funtionalized thiophene nucleus

“…As a result, the isomeric structure 10, if isolated, would be expected to display a downfield shift for the thioamide NH proton, typically in the range of δH ca. 13.00-14.00 ppm as reported by different authors in similar protocols [29][30][31][32][33][34][35][36]. The lack of signals arising from the thione function in the downfield region at δC value above 169 ppm [36][37][38][39], in the 13 C NMR spectrum of the product isolated from the studied reaction, is also evidence in favor of the structure 9.…”

“…In the 1 H NMR spectrum of 10, a signal for the triazoline CS-NH proton was observed to be shifted downfield to 13.75 ppm. This downfield shift of NH proton in this reaction product as compared to the corresponding NH proton in compound 9 can be rationalized on the basis of the deshielding effect of the adjacent CS group, thus establishing the thione structure, 10, [29][30][31][32][33][34][35]. Conclusive evidence for the proposed structure 10 was provided by 13 C NMR spectrum of the isolated product, in which an important signal at δC 171.6 ppm was detected.…”

Design, synthesis, DFT, docking studies and ADME prediction of some new coumarinyl linked pyrazolylthiazoles: Potential standalone or adjuvant antimicrobial agents

“…( Fig 1 ) are used clinically besides using for agricultural pest management [ 18 – 22 ]. Especially, 3,5-dimethyl-4-aryldiazenylpyrazole derivatives have been reported to exhibit cytotoxic [ 23 ], antioxidant [ 24 ], analgesic [ 25 ] and significant antimicrobial potential [ 26 ]. On the other side, compounds containing coumarin moiety ( Fig 1 ) have also been proved as a potent antimicrobial, antitumor, anticoagulant, antiviral, and anti-inflammatory agents [ 23 , 24 , 27 – 31 ].…”