Thiazolyl Derivatives Research Articles

Antimicrobial study of ruthenium and iridium half-sandwich complexes containing fluorenyl hydrazonothiazole derivative ligands

A series of six new hydrazineyl-thiazolyl mononuclear complexes (1–6) of the type [(arene)M(κ2 (N∩N)-L)Cl] (M = Ru, Ir, arene: p-cymene or Cp* (pentamethyl cyclopentadienyl); L = bidentate substituted thiazolyl derivatives) have been synthesized and characterized. The complexes have been isolated as neutral mononuclear N∩N chelating metal complexes. Complexes 1–6 were characterized by IR, UV–Vis, NMR, and ESI-MS spectral methods. The solid-state molecular structures of 3 and 4 were determined using single-crystal X-ray diffraction and the geometry of the complexes are pseudo-octahedral, similar to piano stool structures. The N∩N binding mode is through the azomethine nitrogen and the nitrogen of the thiazole ring, forming a five-membered chelating ring. The synthesized ligands and complexes were then tested for their antibacterial properties against three strains of bacterial microorganisms, Staphylococcus aureus (+ve), Klebsiella pneumoniae (−ve), and Escherichia coli (−ve).

New BI and TRI-Thiazole copper (II) complexes in the search of new cytotoxic drugs against breast cancer cells

New thiazolyl derivatives (BT and TT) and their copper (II) complexes [Cu2Cl2(BT)2] (Cu-BT) and [Cu4ClO2(TT)2]PF6⋅3.5H2O (Cu-TT) were synthesized and characterized by elemental analysis, 1H NMR and 13C NMR, HRMS, X-ray diffraction, IR and UV–Vis spectroscopies. The crystal structure of Cu-BT shows the formation of a dinuclear complex where each copper(II) center is bonded to two thiazol N atoms, from different BT ligands, one deprotonated amide N atom, an O atom from the ester terminal groups and a chlorine atom. The structure found for Cu-TT is a positively charged tetranuclear moiety containing two deprotonated TT ligands, a chlorine anion, two hydroxide anions acting as bridges between the copper centers and a water molecule. The cytotoxic activity of both copper complexes was evaluated on metastatic breast cancer cell lines, characterized for its rapidly dividing behavior. Both, Cu-BT and Cu-TT, show higher cytotoxic activity against these tumor cells than free BT and TT and also than cisplatin. In addition, we found that both complexes interact with DNA. Consistently, they also show cytotoxicity against a rapidly dividing non-tumor cell line, although with higher IC50, being such interaction and selectivity an indicator of the possible coexistence of more than one mechanism of action.

Application of Docking Analysis in the Prediction and Biological Evaluation of the Lipoxygenase Inhibitory Action of Thiazolyl Derivatives of Mycophenolic Acid.

5-LOX inhibition is among the desired characteristics of anti-inflammatory drugs, while 15-LOX has also been considered as a drug target. Similarity in inhibition behavior between soybean LOX-1 and human 5-LOX has been observed and soybean LOX (sLOX) type 1b has been used for the evaluation of LOX inhibition in drug screening for years. After prediction of LOX inhibition by PASS and docking as well as toxicity by PROTOX and ToxPredict sixteen (E)-N-(thiazol-2-yl)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methylhex-4-enamide derivatives with lengths varying from about 15–20 Å were evaluated in vitro for LOX inhibitory action using the soybean lipoxygenase sLOX 1b. Docking analysis was performed using soybean LOX L-1 (1YGE), soybean LOX-3 (1JNQ), human 5-LOX (3O8Y and 3V99) and mammalian 15-LOX (1LOX) structures. Different dimensions of target center and docking boxes and a cavity prediction algorithm were used. The compounds exhibited inhibitory action between 2.5 μΜ and 165 μΜ. Substituents with an electronegative atom at two-bond proximity to position 4 of the thiazole led to enhanced activity. Docking results indicated that the LOX structures 1JNQ, 3V99 and 1LOX can effectively be used for estimation of LOX inhibition and amino acid interactions of these compounds.

Synthesis of new thiazole and thiazolyl derivatives of medicinal significant-a short review

Synthesis of new thiazole and thiazolyl derivatives of medicinal significant-a short review

Docking analysis targeted to the whole enzyme: an application to the prediction of inhibition of PTP1B by thiomorpholine and thiazolyl derivatives

PTP1b is a protein tyrosine phosphatase involved in the inactivation of insulin receptor. Since inhibition of PTP1b may prolong the action of the receptor, PTP1b has become a drug target for the treatment of type II diabetes. In the present study, prediction of inhibition using docking analysis targeted specifically to the active or allosteric site was performed on 87 compounds structurally belonging to 10 different groups. Two groups, consisting of 15 thiomorpholine and 10 thiazolyl derivatives exhibiting the best prediction results, were selected for in vitro evaluation. All thiomorpholines showed inhibitory action (with IC50 = 4–45 μΜ, Ki = 2–23 μM), while only three thiazolyl derivatives showed low inhibition (best IC50 = 18 μΜ, Ki = 9 μΜ). However, free binding energy (E) was in accordance with the IC50 values only for some compounds. Docking analysis targeted to the whole enzyme revealed that the compounds exhibiting IC50 values higher than expected could bind to other peripheral sites with lower free energy, Eo, than when bound to the active/allosteric site. A prediction factor, E− (ΣEo × 0.16), which takes into account lower energy binding to peripheral sites, was proposed and was found to correlate well with the IC50 values following an asymmetrical sigmoidal equation with r2 = 0.9692.

Synthesis of Oxadiazolyl, Pyrazolyl and Thiazolyl Derivatives of Thiophene-2-Carboxamide as Antimicrobial and Anti-HCV Agents.

Introduction:Three series of pyrazole, thiazole and 1,3,4-oxadiazole, derivatives were synthesized starting from 5-amino-4-(hydrazinocarbonyl)-3-methylthiophene-2-carboxamide (2).Methods:All compounds were investigated for their preliminary antimicrobial activity. They were proved to exhibit remarkable antimicrobial activity against Pseudomonas aeruginosa with insignificant activity towards Gram positive bacterial strains and fungi.Results: In-vitro testing of the new compounds on hepatitis-C virus (HCV) replication in hepatocellular carcinoma cell line HepG2 infected with the virus utilizing the reverse transcription polymerase chain reaction technique (RT-PCR) generally showed inhibition of the replication of HCV RNA (–) strands at low concentration, while, eight compounds; 3a, 6, 7a, 7b, 9a, 9b, 10a and 11b proved to inhibit the replication of HCV RNA (+) and (–) strands at very low concentration range 0.08-0.36 μg/mL.Conclusion:Compounds 7b and 11b displayed the highest anti-HCV and antimicrobial activities in this study.

Synthesis of Some Novel 1,4‐Phenylene‐bis‐thiazolyl Derivatives and Their Anti‐hypertensive α‐blocking Activity Screening

A series of novel 1,4‐phenylene‐bis‐thiazolyl derivatives were synthesized and evaluated for their anti‐hypertensive activities as α‐blocking agents and some of them showed promising activities.

English

English

Stepwise Synthesis of 2-Amino-3-Vinylindolizines Using a Mixture of N-Allyl-2-Halopyridinium Halides and CH Acid Derived from Acetonitrile

N-Allyl-2-bromo- and N-allyl-2-chloropyridinium halides react with malonodinitrile and thiazolyl derivatives of acetonitrile in the presence of a twofold excess of triethylamine to provide nucleophilic substitution products, which undergo Thorpe cyclization smoothly upon treatment with KOH to give the corresponding 2-amino-3-vinylindolizines.

STEPWISE SYNTHESIS OF 2-AMINO-3-VINYLINDOLIZINES USING A MIXTURE OF N -ALLYL-2-HALOPYRIDINIUM HALIDES AND CH ACID DERIVED FROM ACETONITRILE

N -Allyl-2-bromo- and N -allyl-2-chloropyridinium halides react with malonodinitrile and thiazolyl derivatives of acetonitrile in the presence of a twofold excess of triethylamine to provide nucleophilic substitution products, which undergo Thorpe cyclization smoothly upon treatment with KOH to give the corresponding 2-amino-3-vinylindolizines. Authors: N. M. Tverdokhleb and G. E. Khoroshilov. English Translation in Chemistry of Heterocyclic Compounds , 2013, 49 (8), pp 1141-1145 http://link.springer.com/article/10.1007/s10593-013-1355-5

Synthesis, Spectral Characterization and Antimicrobial Activity of Substituted Thiazolyl Derivatives of 2-Quinolones

A series of new 3-(2-substituted amino/substituted hydrazino-1,3-thiazol-4-yl)-4-hydroxy-1-methyl/phenylquinolin-2 (1H)-one hydroiodide 3a-3f and 4a-4f derivatives were prepared by heating 3-Acetyl-4-hydroxy-1-methyl/phenyl quinolin-2 (1H)-one 2a-2b with substituted thiourea and substituted thiosemicarbazide in presence of iodine in n-butanol. The title compounds were characterized on the basis of IR, 1H NMR, 13C NMR and Mass spectral (MS) studies. Further title compounds were evaluated for antibacterial and antifungal by Agar diffusion assay method where as antitubercular activity by Micro-plate Alamar Blue Assay (MABA). Among 12 synthesized novel compounds 3a, 3b, 4d exhibited promising antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa. 3a, 3b, 3e, 4d, 4e showed good antifungal activity against Candida albicans and Aspergillus niger. 3a, 3d, 4d showed good antitubercular activity against Mycobacterium tuberculosis H37Rv strain.

Some heterocyclic azo dyes derived from thiazolyl derivatives; synthesis; substituent effects and solvatochromic studies

A series of azo disperse dyes were synthesized by coupling reaction of N, N-diethylaniline, 2-anilinoethanol and N-phenyl-2,2′-iminodiethanol with diazotized aminothiazolyl derivatives as diazo components. These dyes have been prepared in good yields, and were characterized by UV–Vis, FT-IR and 1H NMR spectroscopic techniques. The effects of solvent polarity and various pH on dyes in the visible absorption spectra were evaluated. All dyes exhibit an excellent correlation coefficient ( r > 0.92) for the linear solvation energy relationship with π* values calculated by Kamlet et al. The influence of the pH on the dyes with electron-donating group implied that these dyes exist in acid–base equilibrium in acidic environment. The effect of substituents of both coupler and diazo component on the color of dyes was investigated as well.

On the Photoisomerization of Thiophene and Thiazole Derivatives

The photochemical isomerization of thienyl and thiazolyl derivatives can be explained by assuming the formation of the Dewar isomer. The isomerization of the Dewar isomer towards the most stable one can account for the observed reaction. No biradical intermediate was found. In the case of thiophene an isomerization of the Dewar thiophene allows the formation of a tricyclic intermediate; a retroelectrocyclic reaction can afford the reaction product. This tricyclic intermediate cannot be formed in the photoisomerization of thiazole derivative.

Synthesis of Some Thiazolyl and Thiadiazolyl Derivatives of Substituted Furan and Pyrrole.

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Synthesis of some thiazolyl and thiadiazolyl derivatives of substituted furan and pyrrole

Abstractmagnified imageFour series of substituted furan and pyrrole have been synthesized. The first series was prepared by cyclization of the key intermediates ethyl 5‐[(4‐substituted thiosemicarbazido)methyl]‐2‐methylfuran‐3‐carboxylates 2a‐2d and 1‐[(4‐acetyl‐5‐methyl‐1H‐pyrrol‐2‐yl)methylene]‐4‐substituted thiosemicarbazides 8a‐8d with chloroacetic acid or (ethyl bromoacetate) to afford the corresponding 4‐oxo‐3‐substituted thiazolidin‐2‐ylidene 3a‐3d or 3‐substituted thiazolidin‐4‐one 9a‐9d. On the other hand, heating of the intermediates 2a‐2d or 8a‐8d with acetic anhydride afforded the corresponding (N‐substituted acetylamino)‐2,3‐dihydro‐[1,3,4]thiadiazol‐2‐yl derivatives 4a‐4d and [1,3,4]thiadiazol‐2‐yl‐N‐substituted acetamide 10a‐10d respectively, while cyclization with p‐bromophenacyl bromide gave rise to the corresponding 3‐substituted thiazol‐2‐yl‐ylidene 5a‐5d and 11a‐11d respectively. Furthermore, 4‐oxo‐3‐substituted thioureido‐thiazolidin‐2‐yl 6a‐6d or 4‐oxo‐thiazolidin‐3‐yl‐3‐substituted thiourea 12a‐12d were obtained by reaction of the intermediates 2a‐2d or 8a‐8d with thioglycolic acid. Some of the synthesized compounds showed promising antimicrobial activities.

Microwave assisted synthesis and pharmacological evaluation of some potent naphtho and benzofuro thiazolyl, oxazolyl, thio and oxadiazalyl derivatives

The substituted 2-acetyl benzofurans on bromination gave substituted 2-(2-bromoacetyl) benzofurans 2a-f. These on reaction with thiourea, urea, thiosemicarbazide and semicarbazide in presence of sodium acetate under microwave irradiation resulted 3a-f, 4a-f, 5a-f and 6a-f respectively. The structures of newly synthesised compounds have been established by elemental analysis, spectral data and screened for antimicrobial, anthelmintic, antiinflammatory and analgesic activities.

Synthesis of Thiazolyl and Thieno Cholestane Derivatives: A Novel Class of Potent Antiinflammatory Steroids.

The reactivity of 5alpha-cholestan-3-one (1) towards the formation of thiazolyl derivatives of potential antiinflammatory activity was studied. Also starting with the aminothieno[2',3': 2,3]cholestane derivative 8 several thiazolylthieno[2',3':2,3]cholestane derivatives were synthesized. The structures of the new compounds were established based on the analytical and spectral data and the in vivo antiinflammatory activities of some of these compounds were investigated.

Design and synthesis of some oxadiazolyl, thiadiazolyl, thiazolidinyl, and thiazolyl derivatives of 1H-pyrazole as anti-inflammatory antimicrobial agents.

Four series of 1H-pyrazole derivatives have been synthesized. The first series was prepared by cyclization of the intermediate 3-(5-bromo-2-thienyl)-1-phenyl-1H-pyrazole-4-carbaldehyde aroyl-hydrazone 4a-c with acetic anhydride to afford the corresponding oxadiazoline derivatives 5a-c. The other series were prepared by the cyclization of the intermediate 3-(5-bromo-2-thienyl)-1-phenyl-4-substituted thiocarbamoylhydrazonomethyl-1H-pyrazole 6a-c with acetic anhydride, ethyl bromoacetate or phenacyl bromide giving rise to 3-(5-bromo-2-thienyl)-1-phenyl-4-[3-acetyl-5-(N-substituted acetamido)-2,3-dihydro-1,3,4-thiadiazol-2-yl]-1H-pyrazoles 7a-c, 3-(5-bromo-2-thienyl)-1-phenyl-4-(3-substituted- 4-oxothiazolidin-2-ylidenehydrazonomethyl)-1H-pyrazoles 8a-c, or 3-(5-bromo-2-thienyl)-1-phenyl-4-(3-substituted-4- phenyl-2,3-dihydrothiazol-2-ylidenehydrazonomethyl)-1H-pyraz oles 9a-c respectively. Some of these compounds showed anti-inflammatory, antibacterial or antifungal activities comparable to that of Proquazone, Ampicillin, or Clotrimazole respectively.

Design and Synthesis of Some Oxadiazolyl, Thiadiazolyl, Thiazolidinyl, and Thiazolyl Derivatives of 1H-Pyrazole as Anti-inflammatory Antimicrobial Agents

Four series of 1H-pyrazole derivatives have been synthesized. The first series was prepared by cyclization of the intermediate 3-(5-bromo-2-thienyl)-1-phenyl-1H-pyrazole-4-carbaldehyde aroylhydrazone 4a—c with acetic anhydride to afford the corresponding oxadiazoline derivatives 5a—c. The other series were prepared by the cyclization of the intermediate 3-(5-bromo-2-thienyl)-1-phenyl-4-substituted thiocarbamoylhydrazonomethyl-1H-pyrazole 6a—c with acetic anhydride, ethyl bromoacetate or phenacyl bromide giving rise to 3-(5-bromo-2-thienyl)-1-phenyl-4-[3-acetyl-5-(N-substituted acetamido)-2,3-dihydro-1,3,4-thiadiazol-2-yl]-1H-pyrazoles 7a—c, 3-(5-bromo-2-thienyl)-1-phenyl-4-(3-substituted-4-oxothiazolidin-2-ylidenehydrazonomethyl)-1H-pyrazoles 8a—c, or 3-(5-bromo-2-thienyl)-1-phenyl-4-(3-substituted-4-phenyl-2,3-dihydrothiazol-2-ylidenehydrazonomethyl)-1H-pyra zoles 9a—c respectively. Some of these compounds showed antiinflammatory, antibacterial or antifungal activities comparable to that of Proquazone, Ampicillin, or Clotrimazole respectively.

2,6-Di(heteroarylvinyl)pyridines as new potential �antitumor agents

A circular dichroism spectroscopic study on the DNA binding ability of 2,6-di(heteroarylvinyl)pyridines (heteroaryl 2-furyl, 2-pyridyl, 2-thiazolyl) provided evidence for the binding of the furyl and thiazolyl derivatives to selected oligonucleotides. The furyl derivative, exhibiting logIC50 = −6.54 for in vitro inhibition against breast carcinoma cells (MCF-7), might represent a new lead compound for structure optimization. Copyright © 2000 John Wiley & Sons, Ltd.