In silico EVALUATION OF THE PHARMACOKINETICS AND TOXICITY OF NOVEL PIPERIDINE DERIVATIVES

Abstract

Introduction. Modern computer modeling methods make it possible to predict the
biological activity and pharmacokinetic properties of compounds at early stages of drug development,
thereby accelerating the identification of promising candidates. Piperidine derivatives are of particular
interest due to their high potential pharmacological value. The aim of this study is to evaluate the
biological activity, pharmacokinetic parameters, and toxicity of novel piperidine derivatives using in silico
methods. Results and discussion. Four new compounds were synthesized via aminomethylation of 1-(2-
ethoxyethyl)-4-ethynylpiperidin-4-ol esters, isolated by column chromatography on Al2O3, and
characterized using physicochemical analysis methods. Biological activity was assessed using the PASS
program, pharmacokinetics via SwissADME, and toxicity via ProTox-III. The compounds demonstrated a
high probability of antibacterial, anti-inflammatory, and analgesic activity, as well as potential
effectiveness in the treatment of osteoporosis, diabetic neuropathy, and neurological disorders.
Pharmacokinetic analysis indicated good absorption and the ability to cross the blood–brain barrier.
According to ProTox-III, the compounds showed predominantly low toxicity (lowest for compound 5,
LD50 = 2935 mg/kg). Conclusion. Compounds 2, 3, 6, and 7 are considered especially promising for
further research due to their high bioavailability and low toxicity. The results support the feasibility of
continued in vitro and in vivo screening of the synthesized compounds.