Registration Number
0218U007142,
0118U003930
, R & D reports
Title
Search for new innovative anticancer agents among 4-thiazolidinones and thiopyrano[2,3-d]thiazoles
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Head
Lesyk R.B., Доктор фармацевтичних наук
Registration Date
19-12-2018
Organization
Danylo Halytsky Lviv National Medical University
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Synthesis of "drug-like" molecules was performed by conjugation of 4-thiazolidinone or thiazole cores with known "biophore" heterocyclic fragments, e.g. the pyridine moiety. Directions for target compounds structure modification via [2+3]-cyclocondensation, aminolysis, Knovenagel and Kleisen-Schmidt reactions have been developed based on the logical-structural approach. It has been shown that pyridinylthioureas are effecient S,N-binucleophiles in the [2+3] -cyclocondensation reactions with various equivalents of dielectrophilic synthon [C2]2+ (ethyl 2-chloroacetoacetate, 2-chloroacetylacetone, monochloroacetic acid, alpha-bromo-gamma-butyrolactone and methyl 2-bromo-3-(4-methylphenyl)propanoate). This allowed to synthesize a series of new pyridinyl-substituted aminothiazoles and 4-thiazolidinones. The design and synthesis of a focused sub-library of C-5 functionalized derivatives of 4-thiazolidinones, espacially 5-cymminalidene-rhodanine-3-carboxylic acids were working out. It has been shown that 1-[4-methyl-2-(pyridine-2,3-ylamino)-thiazole-5-yl]ethanones are efficient reagents in the reaction with aromatic aldehydes in ethanol medium in the presence of potassium tert-butylate as a catalyst. It led to the synthesis of number of 3-aryl-(1-2-pyridylaminothiazol-5-yl)propenones. One-pot process based on a sequential [2+3]-cyclocondensation and a Knovenagel reaction in situ formed 4-thiazolidinone and aromatic aldehydes was developed. Such process is the optimal approach to the synthesis of library of target 5-yliden-2-pyridinyl-aminothiazole-4-ones. the existence of prototropic amino-imine tautomerism for 2-pyridinylaminothiazole-4-ones in solution, and the precence of amino-form in the crystall were confirmed based on complex NMR analysis and x-ray studies of 5-benzyl/alkyl-2-(pyridin-2-yl) aminothiazole-4-ones. The screening studies of pharmacological activity of synthesized compounds led to identification of a number of compounds with anticancer activity and determination of some aspects of structure-activity relationships.
Product Description
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Камінський Д.В.
Крищишин А.П.
Лесик Р.Б.
Лозинський А.В.
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2020-04-02
