Synthesis and Biological Activity of Substituted 2-[2-(Diphenylmethylene)hydrazinyl]-5,5-dimethyl-4-oxohex-2-enoates

Abstract

The synthesis of new substituted 2-[2-(diphenylmethylene)hydrazinyl]-5,5-dimethyl-4-oxohex-2-enoates is described. The synthesis from commercially available starting materials included the preparation of 5,5-dimethyl-2,4-dioxohexanoic acid via Claisen condensation of 3,3-dimethylbutan-2-one (pinacolone) and diethyl oxalate in the presence of sodium methanolate. The resulting acid reacted with (diphenylmethylene)hydrazine to form 2-[(diphenylmethylene)hydrazono]-5,5-dimethyl-4-oxohexanoic acid. The initial 5-(tert-butyl)-3-[(diphenylmethylene)hydrazono]furan-2(3H)-one was obtained by a known literary method: intramolecular cyclisation of 2-[(diphenylmethylene)hydrazono]-5,5-dimethyl-4-oxohexanoic acid under the action of propionic anhydride. 5-(tert-Butyl)-3-[(diphenylmethylene)hydrazono]furan-2(3H)-one entered the decyclization reaction under the action of primary aromatic alcohols to form substituted 2-[2-(diphenylmethylene)hydrazinyl]-5,5-dimethyl-4-oxohex-2-enoates. The presence of equimolar quantities of triethylamine was important; otherwise, the reaction proceeded with low yields. The isolation of target compounds was carried out by fi ltration of the resulting sediment followed by recrystallization. The structure of the compounds obtained was confi rmed by the 1 H and 13 C NMR spectroscopy methods. The resulting substituted esters exist in a solution of deuterated chloroform in one tautomeric form, in contrast to the previously studied solutions of deuterated DMSO, where up to four tautomeric forms were observed. Analgesic and anti-infl ammatory activity of new and previously synthesized compounds of this series has been studied. Analgesic activity was evaluated by the "Hot Plate" test on outbred white mice of both sexes with intraperitoneal injection. Anti-infl ammatory activity was studied on a carrageenan-induced paw edema model with oral administration of the studied substances. One compound possesses both high analgesic and high anti-infl ammatory effects, which causes the prospects for its use as a pharmacologically active substance.

Synthesis, recyclization under the action of methanol and analgetic activity of N'-(5-aryl-2-oxofuran-3(2H)-ylidene)furan-2-carbohydrazides

“…Such a universal structural fragment can be found among the 3-imino-(hydrazinylidene)-furan-2(3H)-one derivatives, which results from their chemical availability due to the scalability of the synthetic methods [8] and the reactivity [9][10][11][12][13][14][15]. For example, the reactions of 3-imino-(hydrazinylidene)-furan-2(3H)-ones derivatives with various nucleophilic reagents lead to the attack on the carbonyl group of the lactone fragment and to the for-mation of acyclic or heterocyclic structures [16][17][18][19][20][21] that retain the pharmacophore fragment of 2,4-dioxobutanoic acid [22][23][24][25][26][27][28][29][30][31][32]. This fragment was found in the structure of various biologically active and natural compounds [33,34], which indicates that this idea is worth developing.…”

Synthesis, intramolecular cyclization and anti-inflammatory activity of substituted 2-(2-(Furan-2-carbonyl)hydrazono)-4-oxobutanoic Acids

“…It was found that 2-(2-(4-R-benzoyl)hydrazono)-4-oxobutanoic and 2-(thiophen-2-ylamino)-4-oxobut-2-enoic acids and their derivativities exhibit analgesic [31,32], anti-inflammatory [16] antimicrobial activity [24] and photoluminescent properties [33,34]. We continue to search for new biologically active compounds with low toxicity [35] and expand the methods for the synthesis of 2,4-dioxobutanoic acid and 3-hydrazonofuran-2(3H)-one derivatives. In this paper, synthesis and anti-inflammatory activity of new 2,4-dioxobutanoic acids derivatives are discussed.…”