Substituted amides and hydrazides of acylpyruvic acids. Part 11. Synthesis and biological activity of 4-aryl-2-hydroxy-4-oxo-2-butenoic acid n-(1,3-thiazol-2-yl)amides

Abstract

As is known, alkyl-, aryl-, and heterylamides of acylpyruvic (or 4-substituted 2-hydroxy-4-oxo-2-butenoic) acid exhibit a broad spectrum of pharmacological properties, including antimicrobial [2 – 14], anticonvulsant [8, 9, 12, 15, 16], antiinflammatory [7, 10, 11, 17 – 23], and analgesic [2, 3, 7 – 20, 22, 23] activity at a low toxicity [3 – 5, 7 – 11, 15, 17 – 21, 23]. It was reported [17] that the group of aroylpyruvic acid thiazolyl amides not containing substituents in the thiazole cycle also includes compounds possessing analgesic and antiinflammatory properties. According to our previous data, N-(1,3-thiazol-2-yl)amide of pivaloylpyruvic acid exhibits a moderate bacteriostatic effect [9] and pronounced analgesic and anti-inflammatory properties [3, 23]. In continuation of the search for new biologically active compounds among acylpyruvic acid thiazolyl amides, we have synthesized a series of 4-aryl-2-hydroxy-4-oxo-2-butenoic acid N-(1,3-thiazol-2-yl)amides (Ia – Iz) substituted at the thiazole ring and studied some pharmacological properties of the obtained compounds. Amides Ia – Iz were synthesized using a well-known method [9, 17, 24] based on the reactions of 5-arylfuran-2,3-diones (IIa – IIg) with 4-ethyl-, 4-aryl-, and 4,5-dimethyl-2-amino-1,3-thiazoles. Amides Ia – Iz appear as readily crystallizable substances of a light-yellow or yellow color, which are insoluble in water and hexane, sparingly soluble in ethanol, acetonitrile, ethyl acetate, dioxane, and benzene, and soluble in DMSO and DMF. For Ar, R, and R see Table 1.

DOI: 10.1007/s11094-005-0056-5

3 Figures and Tables

Cite this paper

@article{Kozminykh2005SubstitutedAA, title={Substituted amides and hydrazides of acylpyruvic acids. Part 11. Synthesis and biological activity of 4-aryl-2-hydroxy-4-oxo-2-butenoic acid n-(1,3-thiazol-2-yl)amides}, author={V. O. Koz’minykh and A. V. Milyutin and Rustam Makhmudov and Alexander Belyaev and E. N. Koz’minykh}, journal={Pharmaceutical Chemistry Journal}, year={2005}, volume={38}, pages={665-669} }