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An acid-functionalized magnetic ionic liquid, 1-acyl-3-methylimidazolium tetrachloroferrate, [AcMIm]-FeCl4 has been utilized for the synthesis of a series of novel highly functionalized coumarinyl-pyrido[2,3-d]pyrimidine-2,4-dione derivatives (3a–3l) by the reactions of various 3-chloro-3-(2-oxo-2H-chromen-3-yl)acrylaldehydes (1) with functionalized aryl, 6-aminouracils. The major significant of the present procedure is the use of task-specific acidic ionic liquid which act as catalyst as well as reaction medium and thus avoiding use of organic solvent and/or protic acid catalyst. The other major advantages of the protocol are (i) shorter reaction time (1 h), (ii) easy work up procedure, (iii) excellent yields of products (91–94%), and (iv) recyclability of catalyst. The compounds (3a–3l) were identified using FT-IR, 1H NMR, and 13C NMR and mass spectroscopic studies. [ABSTRACT FROM AUTHOR]

A series of novel, multifunctional 1,3,4‐thiadiazine derivatives bearing phthalazines, pyridazines and pyrido‐pyridazines (9–13) have been synthesized via the multicomponent reaction of (3‐(2‐bromo‐2‐[2‐chloropyrimidin‐4‐yl]acetyl)‐2‐chlorophenyl)‐2,6‐dichloro benzene‐sulfonamide with thiocarbohydrazide and various anhydrides. The reactions were performed by refluxing the components in mixed ethanol/acetic acid to afford the corresponding products in good to excellent yields. All the synthesized compounds were characterized by analytical and spectral studies. The developed method features short reaction time, simple work‐up without chromatographic separation, and a broad range of substrate applicability. A series of novel multi‐functional 1,3,4‐thiadiazine derivatives bearing phthalazines, pyridazines, and pyrido‐pyridazines (9–13) were synthesized via the multicomponent reaction of (3‐(2‐bromo‐2‐[2‐chloropyrimidin‐4‐yl]acetyl)‐2‐chlorophenyl)‐2,6‐dichloro benzene‐sulfonamide with thiocarbohydrazide and various anhydrides. The reactions were performed by refluxing the components in mixed ethanol/acetic acid to afford the corresponding products in good to excellent yields. [ABSTRACT FROM AUTHOR]

A series of 3-(4-phenylisothiazol-5-yl)-2 H-chromen-2-one ( 6a- l) derivatives has been efficiently synthesized by straightforward sequential reactions. Tandem Vilsmeier Hack reaction/cyclization/bromination/Suzuki cross-coupling reactions were successfully applied to the preparation of title compounds in good-to-high yields. In the synthetic sequences, 3-chloro-3-(2-oxo-2 H-chromen-3-yl)acrylaldehydes ( 2) were found to react with ammonium thiocyanate to yield the corresponding 3-(isothiazol-5-yl)-2 H-chromen-2-ones ( 3). These derivatives were brominated with N-bromo succinamide to yield the corresponding regioselective 3-(4-bromoisothiazol-5-yl)-2 H-chromen-2-one ( 4). Finally, compound 4 was treated with various phenyl/pyrazole/7 H-pyrrolo[2,3-d]pyrimidinyl boronic acids 5a- l in the presence of K2CO3 and Pd catalyst in dimethylformamide to yield the corresponding title derivatives 6a- l. All the synthesized compounds were characterized by analytical and spectral studies. All the final compounds were screened against different cancer cell lines (A549, PC3, SKOV3, and B16F10), and among these compounds, 6b, 6g, 6h, and 6l displayed moderate cytotoxic activity against the tested cell lines. [ABSTRACT FROM AUTHOR]

A facile, green, one-pot multicomponent synthesis strategy was employed to fabricate novel thiazole scaffolds incorporating phthalazine, pyridazine, and pyrido-pyridazine derivatives ( 4a - 4o ). This synthetic route entailed the reaction of an α-halo carbonyl compound ( 1 ) with thiosemicarbazide ( 2 ) and various anhydrides ( 3a - 3o ), utilizing NiFe 2 O 4 nanoparticles as a reusable catalyst in an ethanol:water (1:1) solvent system. The cytotoxicity of the synthesized compounds was meticulously assessed against three cancer cell lines, A375, HeLa, and MCF-7, employing IC 50 values (μM) as the benchmark, and compared to the reference drug erlotinib. Compound 4n displayed remarkable efficacy against A375 (0.87 ± 0.31 μM), HeLa (1.38 ± 1.24 μM), and MCF-7 (1.13 ± 0.96 μM) cell lines, significantly surpassing erlotinib's IC 50 values. Additionally, compounds 4k , 4l , 4m , and 4o demonstrated notable cytotoxicity across all tested cell lines, indicating their potential as effective anticancer agents. In silico docking studies against Hsp82 and Hsp90 proteins indicated that ligands 4k , 4m , 4c , 4j , 4o , and 4l had superior binding affinities compared to erlotinib. ADME analysis showed that compounds 4n , 4j , 4l , 4m , and 4o had favorable pharmacokinetic profiles, including nontoxicity, high human intestinal absorption, and low CYP inhibitory promiscuity. Structure-activity relationship analysis revealed that cyano and benzylidene substitutions significantly enhanced anticancer activity. Overall, the synthesized compounds, particularly 4n , demonstrated high efficacy, favorable binding interactions, and promising pharmacokinetic profiles, making them strong candidates for further development as anticancer agents., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)