A series of novel 1,3,4-thia(oxa)diazole substituted 2-(2,4-dioxothiazolidine-5-ylidene)-acetamides 3a-c, 4 and 5a-k have been synthesized following the acylation reaction of 2-amino-5-aryl-1,3,4-oxadiazoles, 5-amino-1,3,4-thiadiazole-2-thiol and it’s S-alkylated derivatives with 2-(2,4-dioxothiazolidine-5-ylidene)acetyl chloride in dioxane medium. The functionalization of compounds 3b, 3c, 5d and 5e was carried out on their N3 position under N-alkylation conditions with N-aryl-2-chloroacetamides in DMF/ethanol medium yielded the corresponding 2,4-dioxothiazolidine-3,5-diacetic acid diamides 6a-e and 7a-b. The structures of target compounds were confirmed by using 1H NMR spectroscopy and elemental analysis. The antioxidant activity evaluation in vitro of the synthesized compounds was performed by the method of scavenging effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals. As a result, the highly active compound 4, namely 2-(2,4-dioxothiazolidin-5-ylidene)-N-(5-mercapto-[1,3,4]thiadiazol-2-yl)acetamide was found to be the most efficient candidate among all compounds with a radical scavenging ability of 88.9%, which was comparable that for ascorbic acid (92.7%). The experimentally calculated IC50 value of 43.1 μM for compound 4 was lower than for ascorbic acid (50.5 μM).

Following the interaction of 2-chloro-N-(5-aryl-1,3,4-oxadiazole-2-yl) acetamides 1a-b with ammonium thiocyanate in dry acetone, the 5-unsubstituted 2-imino-4-thiazolidinones 4a-b have been synthesized. Compounds 4a-b were subsequently utilized in Knoevenagel condensation with aromatic aldehydes or isatin derivatives to synthesize the series of 5-arylidene/isatinylidene substituted 2-(1,3,4-oxadiazol-2-yl)imino-4-thiazolidinones 5a-h and 6a-d. The structures of target compounds were confirmed by using 1H NMR spectroscopy and elemental analysis. Evaluation of anti-cancer activity in
vitro for the synthesized compounds was performed following the National Cancer Institute protocol against leukemia, melanoma, lung, colon, CNS, ovarian, renal, prostate, and breast cancer cell lines. As a result, the most active compound 5a, namely 2-[5-(4-chlorophenyl)-[1,3,4]oxadiazol-2-ylimino]-5-(4-methoxybenzylidene)thiazolidin-4-one was found to be a highly efficient anti-tumor candidate with average logGI50 and logTGI values of -5.19 and -4.09, respectively

Introduction. Nitrogen-based heterocycles are an extremely important class of organic substances widely used in medicinal chemistry, since more than 60% of drugs and more than 85% of biologically active substances described in the literature contain a Nitrogen-containing heterocycle in their structure. The оbjective of thе prеsent study wаs to synthеsize sоme nоvel antiоxidant аgеnts viа a structurаl mоdification оf еarly оbtainеd 3-(5-mercapto-[1,3,4]oxodiazole-2-yl-methyl)-5,7-dimethyl-3H-thiazolo[4,5-b]pyridine-2-one fоr furthеr pharmаcological scrеening in vitrо as antiоxidants.

Results and discussion. For broadening the scope of mercapto substituteds thiazolo[4,5-b]pyridines, we involved 3-(5-mercapto-[1,3,4]oxodiazole-2-yl-methyl)-5,7-dimethyl-3H-thiazolo[4,5-b]pyridine-2-one into cynoethylation reaction taking the advantage of the good leaving hydrogen atom property of the SH-group. It is established that the most optimal conditions for the introduction of the β-cyanoethyl fragment on the base scaffold thiol group consists of the interaction of 3-(5-mercapto-[1,3,4]oxodiazol-2-yl-methyl)-5,7-dimethyl-3H-thiazolo[4,5-b]pyridin-2-one with acrylonitrile in a pyridine-water medium at a ratio of 5:1, this made it possible to obtain the corresponding 3-[5-(5,7-dimethyl-2-oxothiazolo[4,5-b]pyridin-3-ylmethyl)-[1,3,4]oxodiazol-2-ylsulfanyl-propionitrile. Obtained through the mentioned above reaction compound was subjected to hydrolysis leading to 3-(5-hydroxy-7-methyl-2-oxothiazolo[4,5-b]pyridin-3(2H)-yl) propanoic acid formation. For carboxyl group transformation, the corresponding chloranhydride, which belongs to unstable highly reactive reagents was obtained, so its application in further transformations was carried out without isolation by introducing aromatic amines acylation. The above conversion allowed to obtain a number of suitable propionamides. The antioxidant activity of the synthesized compounds was measured in vitro by the method of scavenging effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals. The present results of аntioxidant  activity have shown that the synthesized compounds demonstrated considerable аntioxidant  effects. Further optimization of the structure to improve biological activity is currently in progress. Conclusions. A sеries of thiazоlo[4,5-b]pyridinе-2-ones pоssessing аntioxidant аctivities wеre preparеd by the structurаl mоdification of thе cоre heterоcycle. Whеn cоmpared with еxisting аntioxidants, some оur cоmpounds wеre fоund to bе mоre potеnt. Thus the cоre fused heterocyclе mаy be cоnsidered as a prоmising scаffold for аntioxidant drug cаndidates devеlopment.

The present microreview systematizes recent advances in the synthetic approaches for novel thiazolo[4,5-b]-pyridines and summarizes pharmacological effects they were found to possess. In particular, modern synthetic techniques for thiazolo[4,5-b]pyridine bicyclic scaffold construction starting from thiazole or thiazolidine derivatives followed by pyridine annulation, which results in the target fused thiazolo[4,5-b]pyridines, are analyzed.

УДК: 616–093+547.789

The present microreview provides access to recent advances in the synthetic approaches to novel thiazolo[4,5-b]-pyridines developed over the last years. This second part presents the overview and analysis of modern synthetic techniques for thiazolo[4,5-b]pyridine bicyclic scaffold construction starting from pyridine derivatives followed by thiazole heterocycle annulation