Synthesis, Reactions and Antitumour Screening of new Enaminones

Abstract

A new series of enaminones derived from 3-acetyl-1-aryl-4-benzoyl-5-phenyl-1H -pyrazoles has been obtained and their reactions with hydrazine hydrate, guanidine hydrochloride, 3-amino-1,2,4-triazole, 2-aminobenzimidazole and active methylenenitriles are described. The mechanisms and regioselectivity of the studied reactions are discussed. The results of screening of the antitumor activity of the enaminones against the human breast cancer cell line MCF-7 revealed that the compounds showed less activity than that of the reference drug doxorubicin. Their activity was found to depend on the nature of the substituent group on the 1-aryl moiety. The order of activity of the series is: H > 4-Cl > 4-MeO > 4-Me > 4-NO 2 .

Bis-enaminones as precursors for synthesis of novel 3,4-bis(heteroaryl)pyrazoles and 3,6-bis-(heteroaryl)-pyrazolo[3,4-d]pyridazines

“…10 Coupling of 2a-c each with a benzenediazonium derivative in ethanol in the presence of sodium acetate gave the corresponding coupling products 3a-c (Scheme 1). Although the latter compounds can exist in the E-and/or Z-forms, their 1 H NMR spectra revealed that they exist only in the form Z-3 (Fig.…”

Site-selectivity in hydrazinolysis of 3,4'-bis-(functionalized carbonyl)-4,3'-bis(pyrazolyl)ketones. A convenient synthesis of 4-(pyrazol-3-yl)-2H-pyrazolo[3,4-d]-pyridazines

“…Both the hydrazonoyl chlorides 6A-C and the enaminones 7 and 8 were prepared as previously described. 14,20 Preparation of 4-[1,5-diphenyl-4-substituted-1H-pyrazole-3-carbonyl]-1-aryl-3-substituted-1H-pyrazoles 9-14. General procedure To a stirred solution of the appropriate hydrazonoyl halide 6 (5 mmol) and the enaminone 7 (1.94 mmol) in dry benzene (30 mL), was added triethylamine (0.5 ml) and the mixture was refluxed for 20 h. The precipitated triethylamine hydrochloride was filtered off, and the filtrate was evaporated under reduced pressure.…”

Theoretical Study of the Proton Transfer in Enaminones

“…They are typical push-pull systems in which the amine group pushes and the carbonyl pulls electron density and have the ability to function both as ambident nucleophiles and as ambident electrophiles (Michael et al, 1999;Almazroa1 et al, 2004;Ruffino and Zanetti, 2009). The carbonyl group, conjugated with the enamine moiety, gives this system enough stability to be easily prepared, isolated and stored under atmospheric conditions at room temperature (Junior et al, 1999;Shawali, 2010). Enaminones are known to possess a variety of medicinal properties including anticonvulsant, antimalarial, antiinflamatory, antitumor and cardiovascular effects (Chaaban et al, 1979;Purnami et al, 2009).…”