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A synthesis of novel bis-thiazoles, linked to quinoxaline as novel hybrid molecules, was accomplished in good yields by the reaction of the appropriate α-haloketones or α-keto-hydrazonoyl chlorides with the corresponding bis(hydrazinecarbothioamide) in ethanol/dimethylformamide (EtOH/DMF) at reflux in the presence of a few drops of triethylamine (TEA). The reaction of the appropriate thioamide with the corresponding bis(2-bromoethanone) yielded novel bis-thiazoles. Furthermore, by reacting bis(2-bromoethanone) with the appropriate 4-amino-3-mercapto-1,2,4-triazole derivatives, novel bis(5,6-dihydro-s-triazolo[3,4-b]thiadiazines) linked to quinoxaline moiety were obtained in good yields. The starting bis-thiosemicarbazone was obtained by reacting 1,1'-((quinoxaline-2,3-diylbis(oxy))bis(4,1-phenylene))diethanone with thiosemicarbazide in EtOH containing a few drops of acetic acid (AcOH) at reflux. On the other hand, the 1,1'-((quinoxaline-2,3-diylbis(oxy))bis(4,1-phenylene))bis(2-bromoethanone) was obtained from the corresponding bis(acetyl) derivative upon treatment with N-bromosuccinimide (NBS) in the presence of p-toluenesulfonic acid (p-TsOH), respectively. Structures of new compounds were confirmed using elemental analyses and spectral data. [ABSTRACT FROM AUTHOR]

A new series of bis(4H‐chromene), bis (pyrano[3,2‐c]chromene), and bis (pyrano[2,3‐c]pyrazole) each linked to the piperazine core via ether linkages was synthesized. The target compounds are probably formed through a three‐component reaction involving two equivalents of each malononitrile and the corresponding active methylene compounds, such as dimedone, 4‐hydroxycoumarine, or 5‐methyl‐2,4‐dihydro‐3H‐pyrazol‐3‐one. Several spectral methods and elemental analyses were used to deduce the chemical structures of the novel compounds. Furthermore, all synthesized compounds were tested for antimicrobial activity, which revealed promising inhibitory results against a variety of multidrug‐resistant microbial strains. These findings were compared to those obtained in the in silico molecular docking study. The docking results improved the activity of new derivatives as potentially effective antimicrobial agents. [ABSTRACT FROM AUTHOR]

A synthesis of novel hybrid molecules containing thiazole or bis(thiazoles) each bearing benzofuran and/or benzo[d]thiazole moieties by the reaction of the appropriate thioamide derivatives with the corresponding bis-bromoacetyl derivatives is reported. Mono- and bis(triazolothiadiazine) derivatives based on benzofuran or benzo[d]thiazole moieties were also synthesized in good yields by the reaction of the appropriate bis(bromoacetyl) derivatives with each of 4-amino-5-mercapto-1,2,4-triazoles and their corresponding bis-derivatives. [ABSTRACT FROM AUTHOR]

The synthesis of novel bis(thiazoles) 20a, 20b, 20c and 23a, 23b, 23c is reported. Thus, reaction of 2-bromo-1-(5-methyl-1-phenyl-1 H-pyrazol-4-yl)ethanone ( 6) with the corresponding thioamide derivatives 7a, 7b, in refluxing EtOH in the presence of triethylamine, afforded 4-pyrazolylthiazoles 8a, 8b in good yields. On the other hand, the novel bis(thiazoles) 20a, 20b, 20c and 23a, 23b, 23c were obtained from the reaction of 6 with the corresponding benzaldehyde thiosemicarbazones 19a, 19b, 19c, 22a, 22b, 22c in refluxing EtOH. Compounds 19a, 19b, 19c and 22a, 22b, 22c were obtained by condensation of the corresponding bis(aldehydes) 18a, 18b, 18c and 21a, 21b, 21c with thiosemicarbazide. [ABSTRACT FROM AUTHOR]

A synthesis of novel three-, four-, and sixfold branched 4-phenylthiazolylhydrazones, 4-pyrazolylthiazolyl hydrazones, and thiadiazoles which are linked to a benzene core via phenoxymethyl spacers was reported. The synthetic methodology includes initially formation of poly(aldehyde thiosemicarbazones) 9, 14, and 15 by acid catalyzed condensation of thiosemicarbazide ( 8) with the appropriate poly(aldehydes) 3, 5, and 7, respectively. Subsequent reaction of 9, 14, and 15 with each of 2-bromo-1-phenylethanone ( 10a) and 2-bromo-1-( 4-chlorophenyl)ethanone ( 10b) in refluxing ethanol in the presence of few drops of TEA afforded 11, 16, and 18, respectively, in good yields. On the other hand, the synthesis of the novel poly(4,5-dihydro-1,3,4-thiadiazolyl) derivatives 20, 21a, 21b, and 22 was performed by of 9b, 14a, 14b, and 15a, respectively, in refluxing . [ABSTRACT FROM AUTHOR]

Novel 9-aminoimidazo[1,2-a:5,4-b']dipyridine-6,8-dicarbonitriles were prepared via the Michael addition reaction of readily accessible 2-(3H-imidazo[4,5-b]pyrid-2-yl)acetonitrile with arylidenemalononitriles. The regioselectivity of the reaction was supported by theoretical calculations at the DFT level. In contrast, the reaction of the appropriate bis-arylidenemalononitrile with 2-(3H-imidazo[4,5-b]pyrid-2-yl)acetonitrile under similar reaction conditions gave the corresponding bis[2-(3H-imidazo[4,5-b]pyrid-2-yl)acrylonitriles]. [ABSTRACT FROM AUTHOR]

The target mono- and bis-(6-pyrazolyltriazolo-thiadiazine) derivatives 4a-c and 6a-d were synthesized using a straightforward protocol via reaction of 3-bromoacetylpyrazole 2 with 4-amino- s -triazole-3-thiols 3a-c and bis(4-amino-5-mercapto- s -triazol-3-yl)alkanes 5a-d , respectively. The bis(6-pyrazolyl- s -triazolo[3,4- b ][1,3,4]thiadiazine) derivatives 8a , b and 10 were also constructed by reaction of the triazolo[3,4- b ][1,3,4]thiadiazine-3-thiol 4c with the proper dibromo compounds 7a , b and 9 , respectively. Structures of the new substances were determined by spectroscopic and analytical data. Compounds 4b , 4c , and 6a showed potent cytotoxicity against MCF-7 (IC 50 = 3.16, 2.74, and 0.39 μM, respectively) and were safe against the MCF-10A cells. Compounds 4b , 4c , and 6a also showed promising dual EGFR and CDK-2 inhibition activities, particularly 6a was the most effective (IC 50 = 19.6 and 87.9 nM, respectively), better than Erlotinib and Roscovitine. Compound 6a treatment induced EGFR and CDK-2 enzyme inhibition by 97.18% and 94.11%, respectively, at 10 μM (the highest concentration). Compound 6a notably induced cell apoptosis in MCF-7 cells, increasing the cell population by total apoptosis 43.3% compared to 1.29% for the untreated control group, increasing the cell population at the S-phase by 39.2% compared to 18.6% (control)., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)