A series of new 1,3,4-oxadiazoles and 1,2,4-triazoles were synthesized in order to obtain new compounds with potential analgesic activity. Compounds were evaluated for their analgesic activities by formalin-induced nociception test. Mefenamic acid (as the reference drug) did not show any activity in the early phase of the formalin test, while compounds 7b, 7c, 8c, and 9a significantly reduced the nociception in this phase. However in the late phase of formalin test all of the target compounds and mefenamic acid showed analgesic activity in comparison to control.
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.
Synthesis and Anticonvulsant Activity of New 2-Substituted-5-[2-(2-fluorophenoxy)phenyl]-1,3,4-oxadiazoles and 1,2,4-Triazoles. -Six new heterocycles such as (I) are synthesized and their anticonvulsant effects are determined employing pentylenetetrazole (PTZ)-induced lethal convulsion and maximal electroshock (MES) tests. Oxadiazole derivative (Ic) has considerable anticonvulsant activity both in PTZ and in MES models, whereas compounds (Ia), (Ib), and (Id) display only mild effects in PTZ and MES tests. It seems that the anticonvulsant activity of (Ic) is mediated by benzodiazepine receptors and other mechanisms. -(ALMASIRAD, A.; TABATABAI, S. A.; FAIZI, M.; KEBRIAEEZADEH, A.; MEHRABI, N.; DALVANDI, A.; SHAFIEE*, A.; Bioorg. Med. Chem. Lett. 14 (2004) 24, 6057-6059; Dep. Med. Chem., Fac. Pharm., Tehran Univ. Med. Sci., Tehran, Iran; Eng.) -H. Hoennerscheid 15-237
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