METHOD FOR SELECTION OF ANTI-INFLAMMATORY AGENTS Russian patent published in 2004 - IPC

FIELD: biology, medicine, organic chemistry, pharmacy.

SUBSTANCE: invention relates to a method for selection of new anti-inflammatory agents wherein their molecules comprise the general fragment: carbonyl - phenyl radical - secondary or tertiary amino-group, namely: 1) N-substituted anthranilic acids; 2) N-alkenyl- anthranilic acid arylamides and hydrazides; 3) N-acetyl-N-alkenylanthranilic acid arylamides; 4) N-acylanthranilic acid allylamides. Using model of carragheenin-induced edema in animal experiments an anti-inflammatory effect (AIEexp.) of these compounds is determined. Then parameters of electron structure of each chemical compound are determined and the following indices are selected: dipole moment (P), complete molecule energy (E_HF), molecular mass (M), charges on atoms (q_i) that show maximal effect on the AIE level. Then the following equations of multiparameter regression are developed: for AIEcalculation = -49.74 P + 71.55 E_HF + 0.23 M - 66.34 q_N - 246.59 q_H + 86.34 of the 1-st row; for AIEcalculation = -32.93 P - 0.28 M - 2090.51 q_N - 72.89 E_HF + 61.78 q_H + 434.47 of the 2-d row; for AIEcalculation = -7.25 P - 238.84 E_HF - 0.66 M - 1974.65 q_N + 168.06 of the 3-d row; for AIEcalculation = -31.17 P - 471.20 q_H + 0.44 M + 589.00 q_N + 229. 30 E_HF of the 4-th row + 112.30. Value AIEcalculation is determined, compared with AIE exp. And then by modeling series of chemical compounds with potential biological activity is broadened, parameters of electron structure of these molecules are determined, calculation of value AIE is carried out by equation of multiparameter regression of molecule geometry, compounds with maximal value AIE are selected, synthesis is carried out and structure and anti-inflammatory activity are assayed in animal experiments. Invention provides the development of method for prognosis evaluation of AIE value of chemical compounds. Method provides reducing consumptions for both synthesis and testing biological activity of new chemical compounds.

EFFECT: improved method for selection of agents.

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