Synthesis of Some Imidazo[1,2-a]pyrazine Derivatives and Evaluation of Their Antinociceptive Activity

Abstract

Objective: The imidazopyrazine ring is a biologically active heterocyclic ring. Many hydrazide-hydrazone-possessing compounds have been reported to have interesting bioactivity, such as antibacterial, antifungal, anticonvulsant, anti-inflammatory, antituberculosis, and analgesic activities. In particular, aroyl hydrazides/hydrazone-containing hetero-rings, such as indole, pyridine, and imidazo[2,1-b]pyridine, and imidazo[1,2-a]pyrazine, have attracted special attention. We designed and synthesized N-(4-substitutedbenzylidene) imidazo[1,2-a]pyrazine-2-carbohydrazide (2a-j) derivatives using the two aforementioned pharmacophoric units based on the synthetic procedure indicated in our previous study. Methods: The structures of the compounds were elucidated using H-1-NMR, C-13-NMR, and mass spectroscopy. Ten final compounds were screened for their possible in vivo antinociceptive activity using a hot plate and acetic acid-induced writhing tests. In addition, the potential anticonvulsant activities of these compounds were evaluated using the PTZ-induced seizure test. A rotarod test was performed to examine probable neurological deficits because of the test compounds. Results: In the hot plate tests, none of the test compounds in the series demonstrated a significant effect. However, compound 2f, which was administrated at 100 mg/kg, significantly decreased the number of writhing behaviors in the acetic acid-induced writhing tests, indicating the antinociceptive activity of this compound. The rotarod latencies of mice were not changed by the test compounds. Furthermore, the tested compounds were ineffective in the PTZ-induced seizure tests. Conclusion: Compound 2f bearing 5-benzylidene moiety was determined as the most active compound.