COMPARATIVE ANALYSIS OF PHARMACOKINETIC PARAMETERS AND REACTIVITY OF N-PHENOXYALKYL DERIVATIVES OF 1-(DIPHENYLMETHYL)PIPERAZINE

Abstract

This paper presents a comparative theoretical study of the pharmacokinetic profile and reactivity descriptors of a series of N-phenoxyalkyl derivatives of 1-(diphenylmethyl)piperazine. Using SwissADME and quantum chemical calculations, we evaluated bioavailability descriptors and frontier molecular orbital parameters (FMO). All compounds were found to comply with drug-likeness rules and exhibit high BBB permeability. It was established that modification of the base scaffold with phenoxyalkyl moieties leads to increased lipophilicity and a broader inhibition spectrum of CYP3A4 and CYP1A2 cytochromes. FMO analysis revealed a narrowing of the ΔE energy gap when moving from the base scaffold to the derivatives, correlating with an increase in their chemical softness and polarizability.