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Information × Registration Number 0225U005274, (0125U001945) , R & D reports Title Development of new anesthetic agents popup.stage_title Встановлення залежності тривалості анестизуючої дії від структури циклічної а-амінокислоти у складі бупівакаїну. Одержання нових анестезуючих засобів - аналогів бупівакаїну Head Mykhailiuk Pavlo K., Доктор хімічних наук Registration Date 29-12-2025 Organization Taras Shevchenko National University of Kyiv popup.description1 It is planned to: (a) synthesize new cyclic α-amino acids - analogues of pipecolic acid; (b) incorporate them into the bupivacaine structure; (c) establish the dependence of the action time on the structure of the 3D Fsp3-enriched bioisoster of piperidine in anesthetics; (e) to obtain new anesthetic agents with different strength and duration of action. popup.description2 Bupivacaine, a sodium ion channel inhibitor, has a long history of clinical use in local anesthesia and pain management. However, its systemic toxicity, which can lead to adverse cardiac conditions, poses a significant challenge in clinics. We replaced the central piperidine ring of bupivacaine with three linear spirocyclic moieties and evaluated the effects of the resulting analogues using physicochemical tests and animal studies. We found that, despite being more hydrophobic than the parent drug, the analogues demonstrated an acceptable level of local anesthesia in mice. Notably, the spirocyclic structures exhibited significantly lower toxicity, with increases in the lethal doses of 1.3-, 2.2-, and 5.0-fold for the three tested structures, respectively. Animal studies suggested that this reduced toxicity may be attributed to lower cardiotoxicity, as evidenced by less QRS widening in isolated guinea pig hearts. Our results suggest that further exploration of spirocyclic analogues of local anesthetics is warranted and support the use of spirocyclic azetidines as a replacement for the piperidine ring in drugs. Product Description popup.authors Yehorova Tetiana V. Kyrychok Oleksandr O. popup.nrat_date 2025-12-29 Close