《Synthesis, characterization, and in vivo pharmacological evaluation of novel Mannich bases derived from 1,2,4-triazole containing a naproxen moiety》 was written by Avci, Ahmet; Tasci, Hayrunnisa; Kandemir, Ummuhan; Can, Ozgur Devrim; Gokhan-Kelekci, Nesrin; Tozkoparan, Birsen. Synthetic Route of C5H12N2This research focused ontriazolethione regioselective preparation antinociceptive antiinflammatory mol docking; methoxynaphthylethylmercaptotriazole piperazine Mannich reaction; 1,2,4-Triazole-5-thione N-Mannich derivatives; Anti-inflammatory activity; Antinociceptive activity; Gastric toxicity; Mannich reaction; Naproxen analogs. The article conveys some information:
A new series of 1,2,4-triazole-5-thione Mannich derivatives I (R = Me, 4-fluorophenyl, 4-pyridyl, etc.) containing a naproxen moiety was designed and synthesized to create naproxen analogs, with the aim of developing novel anti-inflammatory/analgesic agents with improved safety profiles. Target compounds were synthesized using classical Mannich reaction (i.e. one-pot three component condensation reaction), by reacting 3-[1-(6-methoxy-2-naphtyl)ethyl]-5-mercapto-1,2,4-triazole, formaldehyde, and diverse secondary amines II in ethanol. Compounds were then evaluated for their potential antinociceptive and anti-inflammatory activities using some validated in vivo methods. Data obtained from acetic acid induced-writhing and carrageenan-induced paw edema tests revealed that all compounds induced peripherally-mediated antinociceptive activities, as well as notable anti-inflammatory effects. The results of hot-plate and tail-clip tests indicated that compounds I (R = Me, Et, 2-fluorophenyl, 4-fluorophenyl, 4-methylphenyl, 4-acetylphenyl) have also centrally-mediated antinociceptive activities in addition to their peripherally-mediated effects. Mol. docking studies were performed to investigate the putative binding modes of the interactions between all compounds and COX-1/COX-2 enzymes using AutoDock Vina software. Docking of the compounds into the COX-2 active site produced binding interactions that are essential for COX-2 inhibitory activity. None of the compounds in the serial, except for I (R = Boc and 4-acetylphenyl), induced significant gastrointestinal irritation. Overall, the results indicated that triazole Mannich bases bearing a naproxen moiety potentially represent a novel class of antinociceptive and anti-inflammatory agent with an improved gastric safety profile. In the experiment, the researchers used many compounds, for example, 1-Methylpiperazine(cas: 109-01-3Synthetic Route of C5H12N2)
1-Methylpiperazine(cas: 109-01-3) can be used as mimic template in the preparation of molecularly imprinted microspheres (MIMs). It was also used to prepare the difunctional strong anion-exchange stationary phase from a 1,4-diazacyclohexane derivative..Synthetic Route of C5H12N2
Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics