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Docking assisted design of novel 4-adamantanyl-2-thiazolylimino-5-arylidene-4-thiazolidinones as potent NSAIDs$

Docking analysis was used to predict the effectiveness of adamantanyl insertion in improving cycloxygenase/lipoxygenase (COX/LOX) inhibitory action of previously tested 2-thiazolylimino-5-arylidene-4-thiazolidinones. The crystal structure data of human 5-LOX (3O8Y), ovine COX-1 (1EQH) and mouse COX-2 (3ln1) were used for docking analysis. All docking calculations were carried out using AutoDock 4.2 software. Following prediction results, 11 adamantanyl derivatives were synthesized and evaluated for biological action. Prediction evaluations correlated well with experimental biological results. Comparison of the novel adamantanyl derivatives with the 2-thiazolylimino-5-arylidene-4-thiazolidinones previously tested showed that insertion of the adamantanyl group led to the production of more potent COX-1 inhibitors, as well as LOX inhibitors (increased activity from 200% to 560%). Five compounds out of the 11 exhibited better activity than naproxen; while nine out of 11 showed better activity than NDGA and seven compounds possessed better anti-inflammatory activity than indomethacin.

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Synthesis, characterization and acute anti-inflammatory evaluation of new mefenamic acid derivatives having 4-thiazolidinone nucleus

Mefenamic acid (MA) is one of the non-steroidal anti-inflammatory drugs, it is widely used probably due to having both anti-inflammatory and analgesic activity, the main side effects of mefenamic acid include gastrointestinal tract (GIT) disturbance mainly diarrhea, peptic ulceration, and gastric bleeding. The analgesic effects of NSAIDs are probably linked to COX-2 inhibition, while COX-1 inhibition is the major cause of this classic adverse effects. Introduction of thiazolidinone may lead to the increase in the bulkiness leads to the preferential inhibition of COX-2 rather than COX-1 enzyme. The study aimed to synthesize derivatives of mefenamic acid with more potency and to decrease the drug’s potential side effects, new series of 4-thiazolidinone derivatives of mefenamic acid were synthesized IVa-g. The synthetic procedures for target compounds and their intermediates are designed to be as follows: Acylation of secondary amine of mefenamic acid by chloroacetylchloride to produce compound (I), then reaction between compound (I) and hydrazine hydrate to form hydrazine derivative of mefenamic acid (compound II). After that, Schiff base formation by addition of seven benzaldehyde derivatives and finally, cyclization in presence of thioglycolic acid to form 4-thiazolidinone heterocyclic ring. The characterization of the titled compounds has been established on the basis of their spectral FTIR, 1HNMR data, and by measurements of their physical properties. In vivo acute anti-inflammatory effect of the synthesized compounds was evaluated in rats using egg-white induced edema model of inflammation. The tested compounds and the reference drug produced significant reduction of paw edema with respect to the effect of dimethyl sulfoxide 10%v/v (control group). Compound IVe showed more potent effect than mefenamic acid at 240-300 min, while at time 300 min, compounds IVa and IVd exhibit more potent anti-inflammatory effect than mefenamic acid (50mg/kg, i.p.) as they reduced paw edema significantly more than mefenamic acid at mentioned intervals (p<0.05) . On the other hand compound IVc exhibited lower anti-inflammatory effect. If you are interested in 2682-49-7, you can contact me at any time and look forward to more communication. COA of Formula: C3H5NOS

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Acid-Catalyzed Synthesis of Thiazolidin-4-ones

A two-steps synthesis of thiazolidin-4-ones, from alpha-tetralone 6 or thiochroman-4-one 7, catalyzed by acids is described. The reactions of alpha-tetralone 6 or thiochroman-4-one 7, with substituted thiosemicarbazides, under AcOH or heteropolyacid (HPAs) catalysis afford thiosemicarbazones 8 and 9 in excellent yields. Condensations of the previous compounds 8 and 9 with alpha-bromoester, under sulfuric acid or heteropolyacid catalysis, yield the corresponding thiazolidin-4-ones 10 and 11.

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Crystal structure of methyl (Z)-2-[(Z)-3-methyl-2-({(E)-1-[(R ?)-4-methylcyclohex-3-en-1-yl]ethylidene}hydrazinylidene)-4-oxothiazolidin-5-ylidene]acetate

The new title 4-thiazolidinone derivative, C 16 H 21 N 3 O 3 S, was obtained from the cyclization reaction of 4-methyl-3-thiosemicarbazone and dimethyl acetylenedicarboxylate (DMAD). The cyclohexylidene ring has an envelope conformation with the stereogenic centre C atom as the flap. Its mean plane makes a dihedral angle of 56.23(9) with the thiazolidine ring mean plane. In the crystal, molecules are linked by C – H?O hydrogen bonds forming chains propagating in the [001] direction. Within the chains there are offset pi-pi interactions between the thiazolidine rings of inversion-related molecules [centroid-centroid distance = 3.703(1)A]. The chains are linked by further C – H?O hydrogen bonds, forming slabs parallel to the ac plane.

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A NEW SYNTHESIS OF HETEROCYCLES VIA CARBONILATION OF AMINES WITH CARBON MONOXIDE IN THE PRESENCE OF SELENIUM

Amines which contain a second functional group in the appropriate position react with carbon monoxide in the presence of selenium to form heterocyclic derivatives in which carbon monoxide is incorporated.For instance, diamines, aminoalcohols, and their related compounds undergo carbonylation to give cyclic ureas, urethanes and the corresponding carbonylated compounds.For diamines and amino alcohols with more than two carbon atoms between the functional groups, intermolecular carbonylative coupling takes place competing with the intramolecular reaction.High selectivity has been attained under specified reaction conditions.Anilines having cyano or acetyl groups on the ortho position afford new classes of selenium-containing heterocycles.In these reactions, carbamoselenoate has been suggested as the common key intermediate.

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Concise and Additive-Free Click Reactions between Amines and CF3SO3CF3

Trifluoromethyl trifluoromethanesulfonate has proved to be an excellent reservoir of difluorophosgene and a promising click ligation for amines in the preparation of urea derivatives, heterocycles, and carbamoyl fluorides under metal- and additive-free conditions. The reactions are rapid, efficient, selective, and versatile, and can be performed in benign solvents, giving products in excellent yields with minimal efforts for purification. The characteristics of the reactions meet the requirements of a click reaction. The use of trifluoromethyl trifluoromethanesulfonate as a click reagent is advantageous over other ?CO? sources (e.g., TsOCF3, PhCO2CF3, CsOCF3, AgOCF3, and triphosgene) because this reagent is readily accessible; easy to scale up; and highly reactive, even under metal- and additive-free conditions. It is anticipated that CF3SO3CF3 will be increasingly as important as SO2F2 as a click agent in future drug design and development.

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A green approach for organic transformations using microwave reactor

Microwave-assisted organic transformation (MAOR) is presently gaining wide popularity in the field of organic synthesis. The conventional heating technique is gradually being removed from the laboratory and a novel microwave heating technique established to be used in both academia and industry. As compared to the classical organic methodology, the green technology tools have several advantages like dramatically reduced reaction times, improved yields, site selectivity, and the increased product purities with simplification of work-up procedures. In the current study, we have briefly described the overview of recent developments and applications of microwave irradiation in organic transformation with schematic compiling of the organic reactions, bioactive heterocyclic compounds, and so on. This review also presents a critical analysis of the various advantages of microwave irradiation in organic synthesis/transformation compared to the classical or conventional heating. So, we believe that our current study of the green microwave heating technique will be highly beneficial for the researchers from both academia and industry in their near future.

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Microwave assisted one pot synthesis of some 2-(substituted) phenyl-3-pyridin-2-yl-1,3-thiazolidin-4-ones under solvent free conditions

We have reported an efficient, operationally simple, environmental benign one pot synthesis of Some 2-(Substituted) Phenyl-3-Pyridin-2-yl-1,3-Thiazolidin-4-Ones Under Solvent Free Conditions (a-f) by a mixture of equimolar quantities of 2-amino pyridine, substituted benzaldehyde and thioglycolic acid with a pinch of anhydrous zinc chloride was heated in a microwave oven for 10-15 min. The progress of the reaction was monitored by TLC. The yields were in the range of 61-86 %. Synthesized compounds were screened for antimicrobial activities against E. coli as Gram negative bacteria and S. aureus as Gram positive bacteria. Some of the compounds displayed pronounced biological activity. The structures of synthesized compounds were elucidated on the basis of spectral (1H NMR,!3 C NMR and IR) and elemental analysis.

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Methods of Screening Agents for Activity Using Teleosts

The present invention provides methods of screening an agent for activity using teleosts. Methods of screening an agent for angiogenesis activity, toxic activity and an effect cell death activity in teleosts are provided. Methods of screening an agent for an activity in the brain or central nervous system in zebrafish are provided. The invention further provides high throughput methods of screening agents in multi-well plates.

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A conceptual review of rhodanine: current applications of antiviral drugs, anticancer and antimicrobial activities

Rhodanines are accepted as advantaged heterocycles in medicinal chemistry as one of the 4-thiazolidinones subtypes. The aim of this paper is to analyze the features of rhodanine and its application in pharmacy and medicine. Some of the properties of rhodanine such as antiviral, anticancer, antimicrobial, and drug discovery have recently been reported. Although there are still vague points in the structure and mechanism of polymerization of this substance, there is a significant increase in the use of rhodanine in medicine. In this review paper, it can be said that we have provided a general overview of the recent advances in the rhodanine-based material which its application is more in the field of drug discovery and anticancer activity. The review starts with a summary of the antiviral activity of rhodanine-based materials and nanocomposites in general. Then in the next step, the detailed description is followed on their applications in the fields of anticancer activity, drug discovery, and an innovative type of rhodanine (RH) and thiohydantoin (TH) derivatives were created and combined in order to recognize tau pathology in the brains of patients with Alzheimer?s disease (AD). Through this review, we hope to promote rhodanine and its role in medicine and pharmacy becomes more prominent.

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