Synthesis, analgesic and anti-inflammatory activities of new methyl-imidazolyl-1,3,4-oxadiazoles and 1,2,4-triazoles

Abstract

BackgroundLong-term clinical employment of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with significant side effects including gastrointestinal (GI) lesions and kidney toxicity. In this paper we designed and synthesized new imidazolyl-1,3,4-oxadiazoles and 1,2,4-triazoles by molecular hybridization of previously described anti-inflammatory compounds in the hope of obtaining new safer analgesic and anti-inflammatory agents.MethodsThe target structures were synthesized by preparation of 5-methyl-1H-imidazole-4-carboxylic acid ethyl ester 5. The reaction of hydrazine hydrate with this ester afforded the 5-methyl-1H-imidazole-4-carboxylic acid hydrazide 6 which was converted to target compounds 7-15 according to the known procedures. In silico toxicity risk assessment and drug likeness predictions were done, in order to consider the privileges of the synthesized structures as drug candidates.Results and discussionThe analgesic and anti-inflammatory profile of the synthesized compounds were evaluated by writhing and carrageenan induced rat paw edema tests respectively. Compounds 8, 9 and 11-13 and 15 were active analgesic agents and compounds 8, 9 and 11-13 showed significant anti-inflammatory response in comparison with control. Compounds 11 and 13 were screened for their ulcerogenic activities and none of them showed significant ulcerogenic activity. The active Compounds 11 and 12 showed the highest drug likeness and drug score.ConclusionsThe analgesic and anti-inflammatory activities of title compounds were comparable to that of standard drug indomethacin with a safer profile of activity. The results revealed that both of oxadiazole and triazole scaffolds can be determined as pharmacophores. The in silico predictions and pharmacological evaluations showed that compounds 11 and 12 can be chosen as lead for further investigations.

Pyrazolyl-Tetrazoles and Imidazolyl-Pyrazoles as Potential Anticoagulants and their Integrated Multiplex Analysis Virtual Screening

“…Fragment-based parameters of drug likeness and drug score were evaluated using Osiris Property Explorer version 2.0 49 as previously described. 50 Analysis from Osiris Property Explorer software revealed that all 4,5-dihydro-1H-imidazolyl pyrazoles derivatives (5a-g) presented a better fragmentbased drug likeness profile in comparison with the pyrazolyl-1H-tetrazole substituted analogs (Figure 9a), suggesting the improved pharmacophoric profile of 4,5-dihydro-1H-imidazolyl pyrazoles rings in comparison with analogs tetrazoles. The combined analysis of druglikeness, aqueous solubility (clog S), partition coefficient of n-octanol/water (clog P) and molecular weight values corroborates to such profile revealing better overall drug score values for the 5a-g series in comparison with the 1a-g series (Figure 9b).…”

“…Apixaban and argatroban were used as controls for FXa and thrombin, respectively. Experimental IC 50 values were based on a substrate concentration of 250 µM and were obtained by fitting a normalized response of FXa catalytic activity vs. inhibitor concentration to nonlinear regression models using Matlab. 70 Ki values of the inhibitory molecules were determined by fitting the initial velocity vs. substrate concentration data to nonlinear regression models using the GraphPad Prism software, 71 The Ki values are expressed as final assay concentrations.…”

Design, synthesis, antimicrobial evaluation, and molecular docking studies of novel symmetrical 2,5‐difunctionalized 1,3,4‐oxadiazoles

“…1,3,4‐Oxadiazoles are valuable five‐membered aromatic heterocycles that possess a wide range of biological properties, including antibacterial, antifungal, antiviral, anti‐inflammatory, antiparasitic, and anti‐HIV activities. Some examples of drugs used in clinical medicine, containing the 1,3,4‐oxadiazole unit, are furamizole, which is an antibiotic drug, and raltegravir, an antiretroviral medication used to treat HIV infection (Figure ).…”

Synthesis and Anti-Inflammatory Activity Evaluation of 5-(1-Benzyl-1H-[1,2,3]Triazol-4-yl)-4-Phenyl- 4H-[1,2,4]Triazole-3-Thiol Derivatives

“…9 It was reported that triazole compounds exhibited kinds of pharmacological abilities, such as anti-inflammatory, analgesic, antinociceptive, antiepileptic etc. [10][11][12][13][14][15][16] 1,2,3-Triazole and 1,2,4-triazole all possess anti-inflammatory activity. [11][12][13]16 In order to search new compounds with higher anti-inflammatory activities and lower toxicity, 1,2,3-triazole and 1,2,4-triazole derivatives were designed on the basis of association principle.…”

“…[10][11][12][13][14][15][16] 1,2,3-Triazole and 1,2,4-triazole all possess anti-inflammatory activity. [11][12][13]16 In order to search new compounds with higher anti-inflammatory activities and lower toxicity, 1,2,3-triazole and 1,2,4-triazole derivatives were designed on the basis of association principle. All of these 5-(1-Benzyl-1H- [1,2,3]triazol-4-yl)-4-phenyl-4H- [1,2,4] triazole-3-thiol derivatives were synthesized, and then the anti-inflammatory activities (in vitro) were evaluated.…”