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p-Fluorophenacyl chloride (1) was used as a building block for the preparation of new tetra-substituted thiophene derivatives. The basic-catalyzed reaction of 1 with various thiocarbamoyl compounds such as 2-acetyl-2-substituted-thioacetanilides 2a,b, 3-arylazo-4-mercapto-4-phenylamino-buten-2-ones 5a–c, ethyl 2-arylazo-3-mercapto-3-phenylamino-acrylates 8a–c, N-aryl-2-cyano-3-mercapto-3-phenylamino-acrylamides 11a–c, N-aryl-2-(mercapto(phenylamino)methylene)-3-oxo-butanamides 14a–c, and 2-mercapto-4,6-dimethylnicotinonitrile 17 led to the production of their corresponding substituted thiophene compounds 4a–b, 7a–c, 10a–c, 13a–c, 16a–c, and 19 in moderate yields. The newly synthesized thiophene compounds were deduced according to FTIR, 1H NMR, 13C NMR, 19F NMR, and mass analyses along with micro-analytical data. The synthesized thiophene compounds were tested to evaluate their antibacterial and antioxidant activities. The majority of the synthesized thiophenes showed good to moderate anti-bacterial and antioxidant activities. The hydroxythiophene compound 4a showed extremely high antibacterial activity with inhibition zones 15–21 mm (from 60 to 87.5% activity indices). It inhibits bacterial growth and approaches the activity of Ampicillin, which inhibits bacteria with areas of inhibition from 23 to 25 mm. The hydroxythiophene compound 4a showed excellent antioxidant properties (85.9%) relative to the reference, Ascorbic acid (88.0%). [ABSTRACT FROM AUTHOR]

A series of new thiophene derivatives was prepared through nucleophilic substitution reactions of the precursor N-(4-substituted-phenyl)-5-(2-chloroacetamido)-4-cyano-3-methylthiophene-2-carboxamides 4a and 4b with different sulfur and/or nitrogen nucleophilic reagents (namely; mercaptoacetic acid, 2-mercaptobenzothiazole, 5-(phenylamino)-1,3,4-thiadiazole-2-thiol, 2-mercapto-4,6-dimethylnicotinonitrile, 3-arylazo-4-mercapto-4-(phenylamino)-but-3-en-one derivatives, ammonium thiocyanate, piperidine and/or morpholine). The structures of the prepared thiophene compounds were characterized by spectral analysis. Their cytotoxicity was evaluated against two human cancer cell lines (HepG2 and MCF-7) and indicated promising results. Pretreatment of HepG2 cells with the tested compound 4b sensitized the cells to the cytotoxicity of sorafenib, leading to a significant decrease in the IC50 from 3.9 to 0.5 μM. [ABSTRACT FROM AUTHOR]

3-Amino-5-bromo-4,6-dimethyl-1H-pyrazolo[3,4-b]pyridine (2) was utilized as a precursor for the construction of new polyheterocyclic ring systems. It reacted with 4-substituted arylidene malononitriles and/or ethyl acetoacetate to furnish the corresponding pyrido[2',3':3,4]pyrazolo[1,5-a]pyrimidine derivatives 4a–c and 6, respectively. Diazotization of the precursor 2 followed by coupling with ethyl cyanoacetate was the route for the formation of pyrido[2',3':3,4]pyrazolo[5,1-c]triazine derivative 8. The synthesized N-(5-bromo-4,6-dimethyl-1H-pyrazolo[3,4-b]pyridin-3-yl)-2-cyanoacetamide (10) was utilized for the synthesis of 6-amino-4-aryl-1-(pyrazolo[3,4-b]-pyridin-3-yl)-1,2-dihydropyridines derivatives 12a–c via its treatment with three types of arylidene malononitrile. N-(5-Bromopyrazolo[3,4-b]pyridinyl)-2-(4-oxothiazolidin-2-ylidene)acetamide 13 and N-(5-bromopyrazolo[3,4-b]pyridinyl)-2-cyano-2-(4-oxo-3-phenylthiazolidin-2-ylidene)acetamide 15 were picked up through the reactions of 10 with 2-mercaptoacetic acid and/or Ph-N = C = S with BrCH2COOEt. The tricyclic ring system, 9-bromo-3-cyano-2-oxo-pyrido[2',3':3,4]pyrazolo[1,5-a]-pyrimidine derivative 18, was used as building block for the construction of new tetra- and penta-heterocyclic compounds 19, 20, and 21 through its reaction with some bis-nucleophilic reagents; hydrazine hydrate, malononitrile and 4-(4-anisylazo)-1H-pyrazole-3,5-diamine. The newly synthesized pyrazolo[3,4-b]pyridine-based heterocycles were characterized by the IR and 1H NMR spectral techniques and their in vitro antibacterial properties were evaluated. [ABSTRACT FROM AUTHOR]