Synthesis of novel thiazole, pyranothiazole, thiazolo[4,5-b]pyridines and thiazolo[5′,4′:5,6]pyrano[2,3-d]pyrimidine derivatives and incorporating isoindoline-1,3-dione group
Abstract:Background
Thiazole is a core structural motif presents in a wide range of natural products. Thiazole derivatives also have a wide range of medicinal and biological properties.
Results
The reaction of hydrazonoyl halides with 2-(1-(4-(1,3-dioxoisoindolin-2-yl)phenyl)ethylidene)hydrazinecarbothioamidein ethanol and triethylamine yielded 2-(4-(1-(2-(4-(2-Arylhydrazono)-5-s-4,5-dihydrothiazol-2-yl)hydrazono)-ethyl)phenyl)isoindoline-1,3-dione and 2-(4-(1-(2-(5-(2-Arylhydra… Show more
“…The distinctive features in the structure of isolated products were elucidated by spectroscopic tools and elemental analyses. 1 H NMR spectra of products 9a–f showed in each case a singlet signal at δ = 7.40–7.48 ppm corresponding to H-5 of thiazole ring . In IR, the bands of (CO) group of compounds 11a and 11b were revealed at 1700 and 1695 cm –1 , respectively.…”
A novel set of thiazolylhydrazonothiazoles bearing an
indole moiety
were synthesized by subjection reactions of carbothioamide derivative
and hydrazonoyl chlorides (or α-haloketones). The cytotoxicity
of the synthesized compounds was evaluated against the colon carcinoma
cell line (HCT-116), liver carcinoma cell line (HepG2), and breast
carcinoma cell line (MDA-MB-231), and demonstrated encouraging activity.
Furthermore, when representative products were assessed for toxicity
against normal cells, minimal toxic effects were observed, indicating
their potential safety for use in pharmacological studies. The mechanism
of action of the tested products, as inhibitors of the epidermal growth
factor receptor tyrosine kinase domain (EGFR TK) protein, was suggested
through docking studies that assessed their binding scores and modes,
in comparison to a reference standard (W19), thus endorsing their
anticancer activity.
“…The distinctive features in the structure of isolated products were elucidated by spectroscopic tools and elemental analyses. 1 H NMR spectra of products 9a–f showed in each case a singlet signal at δ = 7.40–7.48 ppm corresponding to H-5 of thiazole ring . In IR, the bands of (CO) group of compounds 11a and 11b were revealed at 1700 and 1695 cm –1 , respectively.…”
A novel set of thiazolylhydrazonothiazoles bearing an
indole moiety
were synthesized by subjection reactions of carbothioamide derivative
and hydrazonoyl chlorides (or α-haloketones). The cytotoxicity
of the synthesized compounds was evaluated against the colon carcinoma
cell line (HCT-116), liver carcinoma cell line (HepG2), and breast
carcinoma cell line (MDA-MB-231), and demonstrated encouraging activity.
Furthermore, when representative products were assessed for toxicity
against normal cells, minimal toxic effects were observed, indicating
their potential safety for use in pharmacological studies. The mechanism
of action of the tested products, as inhibitors of the epidermal growth
factor receptor tyrosine kinase domain (EGFR TK) protein, was suggested
through docking studies that assessed their binding scores and modes,
in comparison to a reference standard (W19), thus endorsing their
anticancer activity.
“…Fractional order reactions are common when degradation products participate in subsequent chemical chain reactions, which is probable in the case of thiamine degradation [ 30 , 37 ]. In weakly acidic to neutral solutions (e.g., pH 6), thiamine is susceptible to hydrolysis in which the methylene bridge is broken, resulting in intact pyrimidine and thiazole moieties [ 18 , 34 , 38 , 39 ]. The resulting intact rings are then likely to undergo subsequent reactions.…”
Thiamine (vitamin B1) is an essential micronutrient in the human diet, found both naturally and as a fortification ingredient in many foods and supplements. However, it is susceptible to degradation due to heat, light, alkaline pH, and sulfites, among effects from other food matrix components, and its degradation has both nutritional and sensory implications as in foods. Thiamine storage stability in solution was monitored over time to determine the effect of solution pH and thiamine concentration on reaction kinetics of degradation without the use of buffers, which are known to affect thiamine stability independent of pH. The study directly compared thiamine stability in solutions prepared with different pHs (3 or 6), concentrations (1 or 20 mg/mL), and counterion in solution (NO3−, Cl−, or both), including both commercially available salt forms of thiamine (thiamine mononitrate and thiamine chloride hydrochloride). Solutions were stored at 25, 40, 60, and 80 °C for up to one year, and degradation was quantified by high-performance liquid chromatography (HPLC) over time, which was then used to calculate degradation kinetics. Thiamine was significantly more stable in pH 3 than in pH 6 solutions. In pH 6 solutions, stability was dependent on initial thiamine concentration, with the 20 mg/mL thiamine salt solutions having an increased reaction rate constant (kobs) compared to the 1 mg/mL solutions. In pH 3 solutions, kobs was not dependent on initial concentration, attributed to differences in degradation pathway dependent on pH. Activation energies of degradation (Ea) were higher in pH 3 solutions (21–27 kcal/mol) than in pH 6 solutions (18–21 kcal/mol), indicating a difference in stability and degradation pathway due to pH. The fundamental reaction kinetics of thiamine reported in this study provide a basis for understanding thiamine stability and therefore improving thiamine delivery in many foods containing both natural and fortified thiamine.
“…The anticancer efficacy of compounds 251 (R=Me, Ar=4‐MeC 6 H 4 ; R=Ph, Ar=2‐thiophenyl or 2‐naphthyl) against the MCF‐7 breast cancer cell line was compared with that of the standard anticancer drug doxorubicin . It turned out that to obtain cytotoxicity indicators similar to doxorubicin , it is necessary that the concentration of the obtained compounds 251 be 3–4 times higher than the concentration of the reference standard [141] …”
Section: Syntheses Of Pyrazoles Triazoles Oxazoles Thiazoles Oxadiazo...mentioning
confidence: 99%
“…It turned out that to obtain cytotoxicity indicators similar to doxorubicin, it is necessary that the concentration of the obtained compounds 251 be 3 -4 times higher than the concentration of the reference standard. [141] Noteworthy is the regiolocalization of the double bond and the proton of the NH group at the formed thiazole ring (Schemes 76 -81). If you compare their location in these schemes, they are different.…”
Section: Synthesis Of Thiazoles Oxadiazoles and Thiadiazoles From Hyd...mentioning
The review covers the results of studies published in the literature on the use of hydrazonoyl halides in the synthesis of five‐ (pyrazoles, thiazoles, triazoles, oxa‐ and thiadiazoles), six‐ (oxa‐ and thiadiazines, indazoles, pyridazines, pyrazines, tetrazines) or seven‐membered (benzotriazepine) heterocycles. In the formation of these heterocycles, the main intermediate stage of the reaction is the in situ generation of nitrilimine, which enters into a cycloaddition reaction with substituted acetylenes (including in situ generated benzynes, naphthynes), allenes, activated olefins, anthranilic acid derivatives, organosulfur compounds (mercaptoaldehydes, mercaptocarboxylic acids ) or with fused heterocycles. Examples are given of the formation of heterocycles by replacing the halogen atom from a hydrazonoyl halide molecule with a nucleophilic group, followed by exhaustive intramolecular cyclization into the target compound. There are discussions of reactions in which the cycloaddition of the nitrilimine to the in situ synthesized Knoevenagel condensation product (from CH‐acid compounds, such as di‐ and monocarbonyl compounds, dinitrile malonic acid) occurs, leading to spiro‐linked or conventional pyrazoles. Some syntheses of biologically active representatives are shown.
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