Computer prediction of biological activity spectra of substituted and fused methylxanthines

Abstract

Based on the chemical structure and mathematical algorithm of the Prediction of Activity Spectra for Substances software, computer prediction of possible types of biological activity of 121 substances substituted and fused derivatives of methylxanthine, has been done. The structure of compounds synthesized has been confirmed by modern physical and chemical methods: elemental analysis, UV-, IR-, HNMR- and mass-spectrometry, counter synthesis. The purity of the synthesized compounds has been controlled by thin layer chromatography. These substances are white crystalline powders, odorless, of a bitter taste, insoluble in water, soluble in dimethylformamide and dimethylsulfoxide and practically insoluble in alcohol, ether, chloroform, glacial acetic acid. Chemical structures of tested compounds have been introduced by a computer program “Java 6 Standart Edition” and posted on the official site of biological spectra prediction (http://195.178.207.233/PASSNew/predsct.php) in the form of the original multi-atomic orbital descriptors (Multilevel Neighborhoods of Atoms). The results of the computer prediction of the diuretic activity have been considered positive if the predicted activity probability of the substance Pa has been > 0.5. It has been specified that the newly synthesized derivatives of methylxanthine are able to demonstrate the following pharmacological activities: diuretic, neurotropic, antihypoxic, analgesic, anti-inflammatory and metabolic. By the method of computer prediction for substituted and fused methylxanthine derivatives it has been found that the highest diuretic activity is characteristic of the compound g-6713 - pyrrolidine 1,7-dimethylimidazo[1,2-f]xanthinyl acetate. The substituted and fused derivatives of methylxanthine present a promising group of compounds for further synthesis and screening of new pharmacological substances with diuretic properties.