Carbothioamide Derivatives Research Articles

Chemoselective Route for Synthesis of N‐Aryl‐3‐oxochromeno[2,3‐c]pyrazole‐2(3H)‐carbothioamide Derivatives

AbstractA chemoselective route for the synthesis of chromeno[2,3‐c]pyrazole‐2(3H)‐carbothioamide derivatives by a five‐component reaction of salicylaldehyde, malononitrile, NH2NH2⋅H2O, aryl isothiocyanate, and H2O in EtOH/AcOH mixture is reported. This new protocol has the advantages of high yields, short reaction times, ease of operation, and simple purification. All structures were confirmed by IR, 1H‐ and 13C‐NMR, and MS analyses. A plausible mechanism for this type of reaction is proposed (Scheme 2).

Design, synthesis and anticonvulsant evaluation of N-(benzo[d]thiazol-2-ylcarbamoyl)-2-methyl-4-oxoquinazoline-3(4H)-carbothioamide derivatives: A hybrid pharmacophore approach

Novel N-(benzo[d]thiazol-2-ylcarbamoyl)-2-methyl-4-oxoquinazoline-3(4H)-carbothioamide derivatives were synthesized and evaluation of their anticonvulsant effects was done using various models of experimental epilepsy. Initial anticonvulsant activities of the compounds were investigated using intraperitoneal (i.p.) maximal electroshock shock (MES), subcutaneous pentylenetetrazole (scPTZ) seizure models in mice. The quantitative assessment after oral administration in rats showed that the most active was 2-methyl-4-oxo-N-(6-(trifluoromethoxy)benzo[d]thiazol-2-ylcarbamoyl)quinazoline-3(4H)-carbothioamide (SA 24) with ED50 values of 82.5 μmol/kg (MES) and 510.5 μmol/kg (scPTZ). This molecule was more potent than phenytoin and ethosuximide which were used as reference antiepileptic drugs. To explain the possible mechanism for anticonvulsant action, some of the selected active compounds were subjected to GABA (γ-amino butyric acid) assay and AMPA ((S)-2-amino-3-(3-hydroxyl-5-methyl-4-isoxazolyl) propionic acid) induced seizure test.

Synthesis, anti-inflammatory activity, and QSAR study of some Schiff bases derived from 5-mercapto-3-(4′-pyridyl)-4H-1,2,4-triazol-4-yl-thiosemicarbazide

The purpose of this research is to synthesize better anti-inflammatory compounds derived from 5-mercapto-3-(4′-pyridyl)-4H-1,2,4-triazol-4-yl-thiosemicarbazide (5). 2-Substituted-N-[3-(pyridin-4-yl)-5-sulfanyl-4H-1,2,4-triazol-4-yl]hydrazine carbothioamide derivatives (6a–j)/(7a–e) are synthesized by the condensation of 5 with variously substituted aromatic aldehydes/1H-indole-2,3-diones, respectively, under conventional and microwave irradiation methods. The microwave method is found to be superior with higher chemical yields, tremendous reduction in time, and is environmentally benign as compared to conventional heating method. The chemical structures of the newly synthesized compounds (6/7) have been confirmed by IR, 1H NMR, and 13C NMR spectra and have been evaluated for anti-inflammatory activity by carrageenan-induced acute paw edema method in rats.

Synthesis of a New Class of Tris‐ and Bis(1,3,4‐thiadiazol‐2‐amine) Methyl and Ethyl Tris‐ and Bis‐2‐(2‐(2‐benzoyl hydrazinyl)‐4‐oxothiazolidine) Acetate Derivatives

Hydrazine, carbothioamide derivatives 2, 3, and 4 were synthesized by the condensation of 1, 3, 5‐tri carbonyl tri chloride, Terephthaloyl dichloride, and 1, 4‐dicarbonyl chloride with thiosemicarbazide in presence of pyridine as a solvent. The reaction of compounds 2, 3, and 4 with DMAD or DEAD led to the formation of 4‐oxothiozolidine derivatives (4b–c), (3a-c), and (2c-d). The treatment of compounds 2, 3, and 4 with 1, 4′‐diboromoacetophenone resulted in the formation of thiazole derivatives (2g, 3f, 4f). The treatment of compounds 2, 3, and 4 with sulfuric led to the formation of 4H‐1,2,4‐triazole‐3‐thiol derivatives (2f, 3d, and 4d). The cyclization of compounds 2, 3, and 4 in the presence of 2N NaOH resulted in the formation of compounds 2e‐4e containing two or three [1,2,4]triazole rings which are linked to the benzene ring. These compounds are important and useful monomer for synthesis of various dendrimers.

Synthesis and Antimicrobial Evaluation of New 5-(2-Hydroxyphenyl)-3-(4-(Phenylthio)Phenyl)-1H-Pyrazole-2(5H)-Carbothioamide Analogues of 2-(4-(Phenylthio)Phenyl)-4H-Chromen-4-One

A series of novel 5-(2-hydroxyphenyl)-3-(4-(phenylthio)phenyl)-1H-pyrazole-2(5H)-carbothioamide derivatives have been synthesized via the ring opening of 2-(4-(phenylthio)phenyl)-4H-chromen-4-one with semicarbazide in ethanol and KOH under ultrasonic irradiation. The synthesized compounds were screened for antibacterial and antifungal activity against bacteria Staphylococcus aureus (MRSA E710) and Escherichia coli (25922) and fungi Candida albicans and Aspergillus fumigates, respectively. Some of the tested compounds showed significant antimicrobial activity. IR, 1H NMR, mass spectral data, and elemental analysis elucidated the structures of all the newly synthesized compounds. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental resource: Biological Assay.

Synthesis of linezolid-like molecules and evaluation of their antimicrobial activities

3-Fluoro-4-(morpholin-4-yl)aniline (2), prepared from 3,4-difluoronitrobenzene, was converted to the corresponding Schiff base (3) by treatment with indol-3-carbaldehyde. The treatment of thiourea 4 and carbothioamide derivatives 9 with ethyl bromoacetate or 4-substituted phenacyl bromides generated the corresponding thiazolidinone (5 and 13) and thiazoline (6 and 12) derivatives, respectively. The acidic or basic treatment of carbothioamide 9 produced 1,3,4-thiadiazole (11) or 1,2,4-triazole (10) compounds, respectively. The structural assignments of the new compounds were based on elemental analysis and spectral (IR, ^1H-NMR, ^{13}C-NMR, and LC-MS) data. The antimicrobial activity study revealed that all compounds showed good antitubercular activities.

Synthesis and Biological Evaluation of Novel Homopiperazine Derivatives as Anticancer Agents

In search of new anticancer agents, a series of novel 1-benzhydryl-4-(substituted phenylcarboxamide / carbothioamide)-1,4-diazepane derivatives were designed, synthesized and characterized using 1H NMR, LCMS and elemental analysis. These molecules were evaluated for their anti-cancer activity by trypan blue exclusion and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on B-cell leukemic cell line, Reh. Carboxamide moiety containing derivatives showed good activity compared to the corresponding carbothioamide derivatives. In particular, 4-benzhydryl-N-(3-chlorophenyl)-1,4-diazepane-1-carboxamide showed good activity with IC50 value of 18 µM.

Cyclization of some carbothioamide derivatives containing antipyrine and triazole moieties and investigation of their antimicrobial activities

Acetohydrazide derivative containing both antipyrine and triazole nuclei ( 5) was obtained starting from ethyl hydrazinecarboxylate derivative ( 2) and 4-aminoantipyrine ( 1) by three steps. The treatment of compound 5 with CS 2 afforded the conversion of hydrazide function into 5-mercapto-1,3,4-oxadiazole ring leading to the formation of 7. Then, 7 gave the product containing triazolotriazine moiety ( 9) by the reaction with hydrazine hydrate. The synthesis of the compounds incorporating the 1,3,4-thiadiazole ( 10a– c), 1,2,4-triazole ( 11a– c) or 1,3-thiazole ( 12, 13) nucleus as third heterocycle was performed by the acidic or basic treatment of compounds 6a– c which were obtained from the reaction of 5 with several isothiocyanates, or by the condensation of 6a with two different phenacyl bromides, respectively. The antimicrobial activity study revealed that all the compounds showed good activities except 3– 5.

Synthesis and Biological Evaluation of Dihydroisoquinoline-2(1H)- Carbothioamide Derivatives as TRPV1 Antagonists

TRPV1 receptor is an important analgesia target. Its antagonists are expected to prevent pain perception by blocking the receptor directly. In this letter, eight dihydroisoquinoline-2(1H)-carbothioamide derivatives were designed and synthesized as TRPV1 antagonists. The benzene ring was modified with different substitutional groups. Preliminary biological tests suggested that the new compounds exhibited TRPV1 antagonist activity and different analgesia effects, some of which were promising as analgesia drugs. Keywords: TRPV1, Antagonist, Dihydroisoquinoline-2(1H)-carbothioamide, Analgesia

Synthesis of some new 1,3,4-thiadiazol-2-ylmethyl-1,2,4-triazole derivatives and investigation of their antimicrobial activities

4-Amino-2-[(5-arylamino-4,5-dihydro-1,3,4-thiadiazol-2-yl)methyl]-5-(4-methylphenyl)-2,4-dihydro-3 H-1,2,4-triazol-3-ones ( 3a– c) were obtained in acidic media via the formation of 2-[(4-amino-3-aryl-5-oxo-4,5-dihydro-1 H-1,2,4-triazol-1-yl)acetyl]- N-arylhydrazinecarbothioamides ( 2a– c), and then, compound 3b was converted to methylated derivative, 4. The basic treatment of carbothioamide derivatives, 2a– c, afforded 4-amino-2-[(4-aryl-5-sulphanyl-4 H-1,2,4-triazol-3-yl)methyl]-5-(4-methylphenyl)-2,4-dihydro-3 H-1,2,4-triazol-3-ones ( 5a– c). The alkylation reactions of compounds 4 H-1,2,4-triazol-3-ylmethyl-5-(4-methylphenyl)-2,4-dihydro-3 H-1,2,4-triazol-3-one derivatives ( 5a– c) were performed by using methyl iodide or ethyl bromide in the presence of sodium ethoxide, while the treatment of the same intermediates, 5a– c, with aromatic aldehydes produced 2-{[4-(4-aryl)-5-sulphanyl-4 H-1,2,4-triazol-3-yl]methyl}-4-(arylmethylene)amino-5-(4-methylphenyl)-2,4-dihydro-3 H-1,2,4-triazol-3-ones ( 8a– d). The synthesis of 4-amino-(or arylideneamino)-5-(4-methylphenyl)-2-{[(4-methylpiperazin-1-yl or morpholin-4-ylethyl)methyl]-4-aryl-5-thioxo-4,5-dihydro-1 H-1,2,4-triazol-3-yl}methyl-2,4-dihydro-3 H-1,2,4-triazol-3-ones ( 7a, b and 9) was performed by a one pot three-component Mannich reaction involving the corresponding compounds, 4-(substituted)amino-4 H-1,2,4-triazol-3-ylmethyl-5-(4-methylphenyl)-2,4-dihydro-3 H-1,2,4-triazol-3-one derivatives 5a, b and 8a, methylpiperazine or 2-(4-morpholino)ethylamine and formaldehyde. The newly synthesized compounds were well characterized by elemental analyses, IR, 1H NMR, 13C NMR and mass spectral studies. They were also screened for their microbial activities. The antimicrobial activity study revealed that some of which 2a, c, 3c, 5a– c, 8a– d showed good activity against a variety of microorganisms.

Montmorillonite KSF clay as an efficient catalyst for the synthesis of 1,4-dioxo-3,4-dihydrophthalazine-2(1 H)-carboxamides and -carbothioamides under solvent-free conditions using microwave irradiation

Different 1,4-dioxo-3,4-dihydrophthalazine-2(1 H)-carboxamide and -carbothioamide derivatives were synthesized in a simple and environmentally benign method from the reaction of different phthalic anhydrides with semicarbazide or thiosemicarbazide using montmorillonite KSF clay as solid acidic catalyst and microwave irradiations under the solvent-free conditions in good yields and short reaction times.

3 H-[1,2]Dithiolo[3,4- b]pyridine-3-thione and its derivatives Synthesis and antimicrobial activity

A series of 2-substituted isothiazolo[5,4- b]pyridine-3(2 H)-thiones, isothiazolo[5,4- b]pyridin-3(2 H)-ones, N-substituted 2-sulfanylnicotinamides and the corresponding carbothioamide derivatives were synthesized and evaluated for their antimicrobial activity against several strains of Gram+ and Gram−bacteria and fungi. Chemical syntheses were resumed into a comprehensive cyclic route that enables the reversible conversion for each derivative of the series considered. Among the tested compounds the N-(aralkyl)-2-sulfanylnicotinamides show the highest fungitoxicity (MIC=1.25–5 μg/ml). The best activity towards Gram-positive bacteria was in the range of 2.5–5 μg/ml. Activity against Gram-negative bacteria was generally very poor for all compounds.

The relationship between the RM values and the connectivity indices for pyrazine carbothioamide derivatives

An apparent correlation has been observed between the RM values obtained by reversed-phase TLC and the connectivity indices arithmetically computed for various substituents in a pyrazine carbothioamide system.