Redkin R. Synthesis and biological activity research of the structural analogues of epiphysial hormone melatonin and heterocyclic compounds on their basis

More than 90 target compounds being acyl derivatives of L-tryptophane, 2-[2-(1H-indole-3-yl)-2-oxoacetylamino]benzoic acid, 4,3'-spiro-2-oxoindolyl derivatives of 2-amino-3-R-4H-pyrans, 4-(indole-3-yl)-derivatives of 2-amino-4Н-pyran and 2-amino-4,6,7,8-tetrahydro-1Н-quinoline-5-one comprising aminoalkyne pharmacophore similar to the МТ molecule were synthesized to develop new structural МТ analogs. The structure of the synthesized substances was confirmed by the element analysis, 1H NMR and 13C NMR spectroscopy, mass spectrometry and X-ray diffraction analysis. As a result, particular features of the spatial structure of 4,3?-spiro-2-oxoindolyl-3 and 4-(indole-3-yl) derivatives of 2-amino-3-R-4H-pyran were established. It was determined that the presence of the aminoalkyl pharmacophore in the molecule results in the antioxidant and hepatoprotective action that is similar to MT, and this effect is the most obvious in 4,3'-spiro-2-oxoindoline-3-yl derivatives of the condensed 2-amino-3-R-4H-pyran. A pharmacological screening also discovered compounds having antioxidant, anti-inflammatory, anticoagulant and hypoglycemic activity. Two of the following compounds have been recommended for further studies: 4,3'-spiro[(6-amino-5-carbethoxy-3-methyl-2Н,4Н-pyrano[2,3-c]pyrazolo)-N'-benzyl- 2'-oxindole] being a compound with a high antioxidant and hepatoprotective activity, and 4,3'-spiro[(2-amino-3-cyano-5,6,7,8-tetrahydro-4H-chromen-5-one)-2'-oxindole], a compound having an antioxidant and high anti-inflammatory effect. Draft pharmaceutical regulatory documents have been developed for the above-mentioned compounds