Meta-chlorobenzhydryl urea

A new ureide has been synthesized by acylation of the anticonvulsant and anti-alc. drug galodif N-[(3-chlorophenyl)(phenyl)methyl]urea with succinic anhydride in the presence of some acids.Unlike galodif which is almost insoluble in water, the synthesized ureide is soluble in aqueous media.It is expected to exhibit higher bioavailability and is promising as a liquid drug dosage form and a prodrug with prolonged action.

Mol. docking studies (in Schrodinger and Glide software) showed that the mol. m-Cl-BHU (meta-chlorobenzhydrylurea) is complementary to the benzodiazepine binding site of GABAA receptors.Binding energy was low (-11.14 kcal/mol); m-Cl-BHU interacts with the key amino acids at the α1γ2 interface: Tyr159, Tyr209, and H101 Phe77 with high fit to the dG insertion model: 0.741.Binding of [3H]flunitrazepam with the benzodiazepine site of brain GABAA receptors increased in rats with exptl. alcoholism treated with m-Cl-BHU at a dose of 100 mg/kg for 14 days.Changes in pharmacokinetic parameters (T1/2, Clt, MRT, MET, and AUC) of the model substrate antipyrine in saliva were seen in healthy volunteers and male patients with alcoholism using Galodif (m-Cl-BHU) at a dose of 300 mg/day for 21 days.Elimination of antipyrine in patients with alcoholism was increased due to activation of microsomal cytochrome P 450 in the liver oxidase system.