Cover Image

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

Full Text:

PDF


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

Refbacks

  • There are currently no refbacks.


Copyright (c) 2019 Yulya Victorivna Martynenko, Oleksii Mykolayovich Antypenko, Olexandr Anatolievich Brazhko, Irina Borisivna Labenska, Sergii Ivanovich Kovalenko

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.