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 1 , and R 2 see Table 1.The proposed structures were confirmed by the results of spectroscopic measurements with reference to the known thiazolylamides of acylpyruvic acids [3,9,17]. The biological activity of the newly synthesized compounds Ia -Iz was compared to that of their structural analogs: benzoylpyruvic acid thiazolylamide (Ia¢) [17] and pivaloylpyruvic acid thiazolylamide (III) [3,9,23].The IR spectra of compounds Ia -Iz display intense absorption bands at n = 3312 -3180 cm -1 (assigned to the stretching vibrations of amide NH group), 1695 -1660 cm -1 (stretching vibrations of amide carbonyl groups), and a broad absorption band at 1620 -1595 cm -1 (characteristic of the carbonyl groups of b-dioxo fragments involved in the six-member chelate cycle). From this we infer that amides Ia -Iz in the solid state occur in the X-enol form, which does 665

Methyl (Z)-3-({5-[(E)-(tert-butylamino)methylidene]-4-oxo-4,5-dihydro-1,3-thiazol-2-yl}sulfanyl)prop-2-enoate

“…The thiazole ring system can be found in natural compounds such as thiamine (Baia, et al, 2008) and scleritodermin A (Wu & Yang, 2007). Thiazole derivatives exhibit varied pharmaceutical properties including anticancer (Lesyk et al, 2006(Lesyk et al, , 2007, anticonvulsant (Siddiqui & Ahsan, 2010), antipsychotic (Satoh et al, 2009), antibacterial and antifungal (Abdel-Wahab et al, 2009;Vijaya Raj et al, 2007), antitubercular (Shiradkar, Murahari et al, 2007), antimicrobial (Shiradkar, Kumar et al, 2007), analgesic and anti-inflammatory (Koz'minykh et al, 2004). For synthetic methods for thiazoles, see: Andrushko et al (2001); Bourahla et al (2007); Fakhari et al (2008); Potikha et al (2008).…”

A comparative study on 2-(2-benzylidenehydrazinyl)-4-(3-methyl-3-phenylcyclobutyl) thiazole : X-ray, HF and DFT studies

“…The chemistry of aminothiazoles and their derivatives has attracted the attention of chemists, because they exhibit important biological activity in medicinal chemistry [5]. Thiazole derivatives exhibit different pharmaceutical properties such as anticancer [6,7], anticonvulsant [8], antipsychoticlike [9], antibacterial, antifungal [10,11], antitubercular [12], antimicrobial [13], analgesic and antiinflammatory [14] activities.…”