Synthesis of glibenclamide-pregnenolone conjugate and its relationship with physico-chemical descriptors log P, π, R_m, V_m, P _c and S_t

In this study, a glibenclamide-pregnenolone conjugate was synthesized. The route involved a reaction of substitution of chloride atom involved in the chemical structure of glibenclamide to form the compound 2 using sodium hydroxide. Additionally, the compound 2 was bound to pregnenolone succinate to form the glibenclamide-pregnenolone conjugate (4) in the presence of dicyclohexylcarbodiimide and p-toluene sulfonic acid. To delineate the structural chemical requirements of the compounds 2 and 4, some parameters such as the physico-chemical descriptors log P, π R_m, V_m, P_c and S_t were calculated. The results showed an increase in log P, π R_m, V_m, P_c values for 4 in comparison with compound 2. These data indicate that steric impediment, conformational preferences and internal rotation of compound 4 could influence the degree of lipophilicity of this compound.