14230-00-3Relevant articles and documents
Studies on the reactivity of fused thiazole toward nucleophilic reagents: Synthesis of new thiazolo-derivatives of potential antischistosomal activity
Manhi, Fatma M.,Mahmoud, Madiha R.
, p. 121 - 131 (2005)
Schistosomiasis is considered one of the most important human helminth infection in terms of morbidity and infectivity (Chitsulo et al. Acta Trop 2000, 77, 41; Engles et al. Acta Trop 2002, 82, 139; Shelly et al. Mol Biochem Parasitol 1993, 60, 93). Derivatives of 2-amino-5-nitrothiazoles have shown activity against Schistosoma mansoni (S. mansoni) and Schistosoma haematobium (S. haematobium), but due to their toxic effect we synthesized new derivatives of a heteroaromatic amine with thiazole moiety. Required thiazole derivatives were prepared via 1 and 2. In this work, two batches of animals were used to test the efficacy of 10 derivatives of thiazole against schistosomiasis. The first batch of Swiss albino mice was infected with S. mansoni and was treated with 5 × 50 mg/kg b.w. The second batch of golden hamsters was infected with S. haematobium and was treated with 5 × 100 mg/kg b.w. Parasitological parameters, biochemical studies, and granuloma diameter were estimated. Results indicated that in the case of S. mansoni infected mice, compounds 2 (2-amino-4-thiazoliniminium chloride) and 20 (2,4-diamino thiazole) showed moderate efficacy (50% worm reduction). While compounds 18 (4-dicyanomethylene-4,5-dihydrothiazo-2-yl)- N,N-dimethylimidoformamide) and 21 2-(dimethylamino) methylene-1,3-thiazol-4-yl)-N,N-dimethylimidoformamide) showed 83% and 90% worm reduction with some normalization of liver function and significant reduction in hepatic granuloma diameters. In the case of S. haematobium infected hamsters, compound 15 showed reduction of worms by about 50% with improvement in kidney function. The high effect of compounds 18 and 21 compared to 2, 15, and 20 could be attributed to the dimethylimidoformamide moieties combined with the thiazole ring.
STRUCTURE OF 2-IMINO-5-ARYLIDENE-4-THIAZOLIDINONES
Ramsh, S. M.,Solov'eva, S. Yu.,Ginak, A. I.
, p. 611 - 614 (1983)
It was established by means of PMR spectroscopy that, depending on the method of preparation, 2-imino-5-arylidene-4-thiazolidones exist in the form of various geometrical isomers relative to the exocyclic C=N bond.The E isomers are obtained as a result of condensation of 2-imino-4-thiazolidone with the corresponding benzaldehydes, whereas the Z isomers are formed in the solvolysis of hydroxymethyl and piperidinomethyl derivatives.The geometrical isomers retain their individuality in solutions in d6-DMSO and in ethanol.Upon dissolving in alkali with subsequent neutralization the E isomer of 2-imino-5-benzylidene-4-thiazolidinone is converted to the Z isomer.Reverse conversion of the Z isomer to the E isomer occurs when a solid sample is heated to 180 deg C.
Anti-hepatitis-C virus activity and QSAR study of certain thiazolidinone and thiazolotriazine derivatives as potential NS5B polymerase inhibitors
Hassan, Ghaneya S.,Georgey, Hanan H.,Mohammed, Esraa Z.,Omar, Farghaly A.
, (2019/10/10)
The present study reports on evaluation of anti-HCV activity and QSAR of certain arylidenethiazolidinone derivatives as potential inhibitors of HCV-NS5B polymerase. The pursued compounds involving, 5-aryliden-3-arylacetamidothiazolidin-2,4-diones 4–6(a–f), 5-arylidine-2-(N-arylacetamido)-iminothiazolidin-4-one (10) and their rigid counterparts 5-arylidinethiazolotriazines 13–15(a–f), were synthesized and their structures confirmed by spectral and elemental analyses. The results of NS5B polymerase inhibition assay revealed compound 4e, as the most active inhibitor (IC50 = 0.035 μM), which is four folds greater than that of the reference agent, VCH-759, (IC50 = 0.14 μM). Meanwhile, compounds 4b, 4c, 5a, and 5c, and 13b, 14e and 15c displayed equipotency to 2 folds higher activity than VCH-759 (IC50 values: 0.085, 0.14, 0.14, 0.10, 0.12, 0.09 and 0.07 μM, respectively). Assessment of the anti-HCV activity (GT1a) using human hepatoma cell line (Huh-7.5) illustrates superior activity of 4e (EC50 = 3.80 μM) relative to VCH-759 (EC50 = 5.29 μM). Cytotoxicity evaluation on, Transformed normal cell lines (Human Liver Epithelial-2, THLE-2 and Proximal Tubular Epithelial, RPTEC/TERT1), demonstrate enhanced safety profile of 4e (CC50 = 102.77, 161.37 μM, respectively) compared to VCH-759 (CC50 = 61.83, 81.28 μM, respectively). Molecular docking of the synthesized derivatives to NS5B polymerase allosteric site (PDB: 2HWH) showed similar binding modes to that of the co-crystallized ligand. Moreover, QSAR models were established for the studied thiazolidinones and thiazolotriazines to investigate the molecular characteristics contributing to the observed NS5B polymerase inhibition activity. The obtained results inspire further investigations of thiazolidinones and thiazolotriazine aiming at affording more potent, safe and orally active non-nucleoside NS5B polymerase inhibitors as anti-HCV drug candidates.
Synthesis and biological evaluation of some new Thiazolo[3,2-a][1,3,5] triazine derivatives
Hamama, Wafaa S.,Ismail, Mohamed A.,Shaaban, Saad,Zoorob, Hanafi H.
, p. 2615 - 2623 (2012/10/30)
2-Iminothiazolidin-4-one (1) was utilized for the synthesis of several new thiazolo[3,2-a][1,3,5]triazine derivatives. 3-Phenyl-3,4-dihydro-2H-thiazolo[3, 2-a][1,3,5] triazin-6(7H)-one (2) was prepared according to Mannich procedure. Both compounds 1 and 2 reacted with aromatic aldehydes to afford arylidene derivatives 3-7. Compounds 5-7 were obtained through another two routes of preparation, first when applying Mannich reaction to compounds 3 and 4 and second by reacting compounds 2 with activated olefins 11 catalyzed by triethylamine, also, the reaction of 2 with bis arylidene 16 afforded compound 18. Compound 2 reacted with both mono and di-aromatic diazonium salts to furnish 2-aryl-azothiazolo[3,2-a]triazines 20 and 21 or bis[2-azothiazolo[3,2-a] triazine]phenylene 22, respectively. Thiocarbamoyl derivatives 25 and 26 were prepared through the reaction of active methylene and imino group in 1 with phenylisothiocyanate and carbon disulfide, respectively. Structures confirmation, geometry, and biological evaluation were applied for the newly prepared compounds. Springer Science+Business Media, LLC 2011.
Design, synthesis, and pharmacological evaluation of N-(4-mono and 4,5-disubstituted thiazol-2-yl)-2-aryl-3-(tetrahydro-2H-pyran-4-yl)propanamides as glucokinase activators
Li, Fuying,Zhu, Qingzhang,Zhang, Yi,Feng, Ying,Leng, Ying,Zhang, Ao
supporting information; experimental part, p. 3875 - 3884 (2010/08/05)
A series of N-thiazole substituted arylacetamides were designed on the basis of metabolic mechanism of the aminothiazole fragment as glucokinase (GK) activators for the treatment of type 2 diabetes. Instead of introducing a substituent to block the metabolic sensitive C-5 position on the thiazole core directly, a wide variety of C-4 or both C-4 and C-5 substitutions were explored. Compound R-9k bearing an iso-propyl group as the C-4 substituent was found possessing the highest GK activation potency with an EC50 of 0.026 μM. This compound significantly increased both glucose uptake and glycogen synthesis in rat primary cultured hepatocytes. Moreover, single oral administration of compound R-9k exerted significant reduction of blood glucose levels in both ICR and ob/ob mice. These promising results indicated that compound R-9k is a potent orally active GK activator, and is warranted for further investigation as a new anti-diabetic treatment.
A facile synthesis of 5-arylidene-2-imino-4-thiazolidinones under microwave irradiation
Zhou, Jian-Feng,Sun, Xiao-Jun,Zhu, Feng-Xia,Li, Yan-Lun,Gong, Gui-Xia
experimental part, p. 4182 - 4187 (2009/04/11)
A series of 5-arylidene-2-imino-4-thiazolidinone derivatives were synthesized by the cross-aldol condensation of aromatic aldehydes with 2-imino-4-thiazolidinone in sodium acetate/acetic acid under microwave irradiation. The reactions were completed in 10 min with 63-91% yields, were environmental benign, and had easy workup. Copyright Taylor & Francis Group, LLC.
Heterophase N-aminomethylation of 5-arylidenepseudothiohydantoins by arylamines and aqueous formaldehyde in aromatic solvents: Effect of substituents in the heterocyclic substrate and the aryl amine on the efficiency of the process
Ramsh,Medvedskiy,Uryupov
, p. 948 - 954 (2008/03/12)
We have obtained a series of 3-aryl-7-arylidene-3,4-dihydro-2H-[1,3] thiazolo[3,2-a][1,3,5]triazin-6(7H)-ones by means of heterophase aminomethylation of 2-amino-5-arylidene-1,3-thiazol-4(5H)-ones with aqueous formaldehyde and aromatic amines in benzene or toluene. We explain the effect of substituents in the heterocyclic substrate and the aryl amine on the efficiency of the process within a detailed scheme for one of the possible aminomethylation reaction routes.
Traceless solid-phase synthesis of 2-amino-5-alkylidene-thiazol-4-ones
Pulici, Maurizio,Quartieri, Francesca
, p. 2387 - 2391 (2007/10/03)
2-Amino-5-alkylidene-thiazol-4-ones bearing two diversity points are prepared by a solid-phase strategy exploiting rhodanine as the starting material. Rhodanine is first loaded on bromo-Wang resin, subjected to Knovenagel condensation with aldehydes, and cleaved off the resin in a traceless manner by means of an amine.
SYNTHESIS OF 2-SUBSTITUTED 5-ARYLIDENETHIAZOLIN-4-ONES FROM α,β-UNSATURATED ACYL ISOTHIOCYANATES
Kutschy, Peter,Dzurilla, Milan,Kristian, Pavol,Kutschyova, Kvetoslava
, p. 436 - 445 (2007/10/02)
α,β-Unsaturated acyl isothiocyanates react with N-methylaniline to give thioureas which, when treated with bromine in chloroform, afford benzothiazoline derivatives.Under the same reaction conditions primary amines, diethylamine,piperidine and morpholine
