Structure—Activity (Analgesic) Relationship of a Series of N-Substituted 3,5-Dibromo(H)Anthranilic Acid Amides and Hydrazides Studied Using an Experimental Model in Mice and Molecular Docking of Cyclooxygenases 1 and 2

Molecular docking of 24 N -substituted 3,5-dibromo( H )anthranilic acid amides and hydrazides ( I - XXIV ) with the enzymes cyclooxygenase 1 (COX-1) and 2 (COX-2) is described. The dependences of experimental analgesic activities (AA exp ) on scoring functions (Be COX1 , Ime COX1 , Ki COX1 , Be COX2 , Ime COX2 , Ki COX2 ) and lipophilicity (log P calc ) and ionization constants (pKa calc , pKb calc ) are studied. The optimum regression equation [Eq. (2)] chosen for the search for biologically active compounds with AA is AA calc = –9.058 + 5.315·pKa calc + 7.157·Ime COX1 – 7.382·Be COX1 – 0.003·Ki COX1 – 0.86·Be COX2 (R = 0.80; F = 6.49; S = 4.91; Q 2 LOO = 0.65). The regression equation [Eq. (2)] is verified by predicting the AA (AA calc ) as compared to experimental data (AA exp ) obtained by the hot-plate method with mice for an independent set of six compounds ( XXV - XXX ), which showed a high correlation coefficient (R = 0.713) between AA calc and AA exp .