We have synthetized a number of nicotinic and picolinic acid derivatives with expected anti-seizure activity. One of the important issues in this therapeutical group are pharmacokinetic properties and metabolic stability due to inter- and intra-subject variability. From experimental studies on metabolic stability it appears that more susceptible for liver and kidney metabolism are picolinic acid derivatives. For four derivatives: N-(2-fluorobenzyl)-2-pyridinecarboxoamide (1), N-benzylpyridinecarboxoamide (2), N-benzylnicotinamide (3), N-benzyl-4-(trifluoromethyl)nicotinamide (4), Energy of formation reaction calculated for each compound as a difference between total energy of product and substrates were calculated at the Hartree-Fock 6-31G* level of approximation. These values are -2.37 kcal/mole (1), 6.86 kcal/mole (2), 3.20 kcal/mole (3) and 0.74 kcal/mole (4). It appeared that energy of formation is not a suitable discriminative property to judge stability difference. Thus we calculate the energy of amide bond for studied compounds: E_C-NH = 257.85 kcal/mole (1), E_C-NH = 245.83 kcal/mole (2), E_C-NH = 249.10 kcal/mole (3) and E_C-NH = 253.53 kcal/mole (4).

For compounds (1) and (2) the values of E_C-NH well correlate with the experimental stability data. The results for compounds (3) and (4) suggest that they should be more susceptible to metabolism, but in fact they are stable. It might mean that for compound (1) and (2) the appropriate enzymatic systems exist, while for compounds (3) and (4) active enzymes in liver and kidney are not present.

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