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Directed Search of Biologically Active Compounds Among Hydrogenated Isoindolylalkyl(alkylaryl-,aryl-)carboxylic acids with Quinazoline Fragment that Modify the Carbohydrate Metabolism: Design, Synthesis and Modification

Yulya Victorivna Martynenko, Oleksii Mykolayovich Antypenko, Olexandr Anatolievich Brazhko, Irina Borisivna Labenska, Sergii Ivanovich Kovalenko

Abstract


An effective synthesis of (3H-quinazoline-4-ylidene)hydrazides of N-carboxyalkyl-(arylalkyl-,aryl-)isoindoline-1,3-diones, using activated N-protected aminoacids and 4-hydrazinoquinazoline was proposed in the framework methodology of directed search of hypoglycemic agents (fragment-oriented design, molecular docking). These hydrazides prepared via cyclocondensation under acid catalysis were converted to the corresponding 2-([1,2,4]triazolo[1,5-c]quinazoline-2-yl-)alkyl-(alkylaryl-,aryl-)-hydroisoindole-1,3(2H)-diones. The structure of synthesized compounds was established using IR, 1H and 13C NMR spectroscopy and LC-MS and the features of spectral pattern were discussed. The results of pharmacological screening revealed a series of compounds, that are short-acting hypoglycemic agents like prandial regulators of glucose (Mitiglinide). The SAR analysis showed, that the introduction of a hydrogenated 1,3-dioxoisoindole moiety bonded through linker groups with 4-hydrazinoquinazoline and triazolo[1,5-c]quinazoline cycles is reasonable in the context of searching for short-acting hypoglycemic agents and requires further research.


Keywords


(3Н-quinazoline-4-ylidene)hydrazides of N-carboxyalkyl-(aralkyl-aryl-)-isoindoline-1,3-diones; 2-([1,2,4]triazolo[1,5-c]quinazoline-2-yl-)alkyl-(alkaryl-, aryl-)-hydroisoindole-1,3(2H)-diones; directed search; physico-chemical properties; spectral featu

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DOI: http://dx.doi.org/10.17344/acsi.2018.4731

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