Study of the analgesic potential of 5-aryl-4-aroyl-1-isobutyl-3-hydroxy-3-pyrrolin-2-ones in a behavioral nociception model

Introduction. The high prevalence of pain syndromes among the global population highlights the need for searching for highly potent analgesic agents with a favorable safety profile. 3-Hydroxy-3-pyrrolin-2-one derivatives exhibit diverse pharmacological activities and represent promising compounds for the development of novel analgesic drug candidates with pronounced efficacy.

Aim. To study the degree of analgesic potential of previously unknown 5-aryl-4-aroyl-1-isobutyl-3-hydroxy-3-pyrrolin-2-ones in a hot plate test.

Materials and methods. Newly synthesized 3-hydroxy-3-pyrrolin-2-ones containing an isobutyl substituent at position 1 (I–VI) were the objects of the study. The analgesic efficacy of 6 analog compounds was assessed in vivo using a behavioral nociception model.

Results and discussion. Pharmacological screening demonstrated that the new compounds previously synthesized by the authors exhibited analgesic potential following oral administration in thermal nociception tests. Compound VI demonstrated the most pronounced analgesic activity. Structure–activity relationship (SAR) analysis revealed distinct patterns correlating molecular features with analgesic efficacy. These findings indicate that the newly synthesized 3-hydroxy-3-pyrrolin-2-ones bearing an isobutyl substituent at position 1 exhibit significant analgesic potential (compounds I, III, V, VI).

Conclusion. The obtained 5-aryl-4-aroyl-1-isobutyl-3-hydroxy-3-pyrrolin-2-ones (a series of 6 analog compounds) were tested on a model of behavioral nociception, the relationship between the chemical structure of the substances and their activity was studied, and the main candidate with significant analgesic potential was identified for further study (laboratory sample with code VI).

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