Amit R. Trivedi

Novel dihydropyrimidines as a potential new class of antitubercular agents

A small library of 30 dihydropyrimidines was synthesized and evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H(37)Rv. Two compounds, ethyl 4-[3-(4-fluorophenyl)-1-phenyl-1H-pyrazol-4-yl]-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5 carboxylate 4a and ethyl 4-[3-(4-nitrophenyl)-1-phenyl-1H-pyrazol-4-yl]-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate 4d were found to be the most active compounds in vitro with MIC of 0.02 μg/mL against MTB and were more potent than isoniazid.

Facile one-pot synthesis and antimycobacterial evaluation of pyrazolo[3,4-d]pyrimidines.

The present article describes a facile one‐pot synthesis of a series of eight pyrazolo[3,4‐d]pyrimidines 4a–h which were evaluated for their in‐vitro antibacterial activity against Mycobacterium tuberculosis H37Rv using the Alamar‐Blue susceptibility test and the activity expressed as the minimum inhibitory concentration (MIC) in mg/mL. The compounds 4b, 4c, 4d, and 4g exhibited the best results (1.2 μg/mL) when compared with first‐line drugs such as isoniazid (INH) and rifampicin (RIP). Therefore, this class of compounds could be a good starting point to develop new lead compounds in the treatment of multidrug‐resistant tuberculosis.

Synthesis and biological evaluation of some novel 1,4-dihydropyridines as potential antitubercular agents.

Recent studies showed that 1,4‐dihydropyridine‐3,5‐dicarbamoyl derivatives with lipophilic groups have significant antitubercular activity. In this study, we have synthesized new derivatives of 1,4‐dihydropyridines bearing carbmethoxy and carbethoxy group at C‐3 and C‐5 of the 1,4‐dihydropyridine ring. In addition, 1H‐pyrazole ring is substituted at C‐4 position. These analogues were synthesized by multi‐component Hantzsch reaction. The in vitro antitubercular activity of compounds against Mycobacterium tuberculosis H37Rv was evaluated. The lowest minimum inhibitory concentration value, 0.02 μg/mL and SI > 500, was found for dimethyl 1,4‐dihydro‐4‐(3‐(4‐nitrophenyl)‐1‐phenyl‐1H‐pyrazol‐4‐yl)‐2,6‐dimethylpyridine‐3,5‐dicarboxylate 3f, diethyl 1,4‐dihydro‐4‐(3‐(4‐fluorophenyl)‐1‐phenyl‐1H‐pyrazol‐4‐yl)‐2,6‐dimethylpyridine‐3,5‐dicarbo‐xylate 4c and diethyl 1,4‐dihydro‐4‐(3‐(4‐bromophenyl)‐1‐phenyl‐1H‐pyrazol‐4‐yl)‐2,6‐dimethyl pyridine‐3,5‐dicarboxylate 4e, making them more potent than first‐line antitubercular drug isoniazid. In addition, these compounds exhibited relatively low cytotoxicity.

Synthesis and antimycobacterial evaluation of various 6-substituted pyrazolo[3,4-d]pyrimidine derivatives

Various pyrazolo[3,4-d]pyrimidines carrying a variety of substituents in the 6-position have been synthesised and their ability to inhibit growth of Mycobacterium tuberculosis in vitro has been determined. Compounds 5a, 5b, 6c, 7a, 7b, 8d, 8e and 8f demonstrated a minimum inhibitory concentration (MIC) of <6.25 µg/mL and were found to be active against Mycobacterium tuberculosis strain H37RV. Compound 8d was found to be the most active compound in vitro with a MIC of <6.25 µg/mL and inhibitory concentration IC90 of 1.53 µg/mL.

Synthesis and antimicrobial evaluation of novel substituted pyrimidine scaffold

Synthesis and biological evaluation of substituted pyrimidine derivatives containing 4-amino and 5-cyano substituted derivatives are described. Biginelli typed three component reactions between an aldehyde, malononitrile, and a urea constituent give a rapid facile pyrimidine ring. The constitution of the products has been delineated by elemental analysis and spectral analysis. The products were assayed for their in vitro biological assay antibacterial activity against S. pyogenes MTCC-442, S. aureus MTCC-96, E. coli MTCC-443, and B. subtilis MTCC-441 bacterial strain and antifungal activity against Aspergillus niger MTCC-282 and Candida albicans MTCC-227 at different concentrations, which compared with Ampicillin, Chloramphenicol, Ciprofloxacin, Norfloxacin, and Griseofulvin as standard drug which are presented.

Simple and efficient synthetic routes to bioactive s-triazinyl dithiocarbamate derivatives

Series of 2,4-diarylamino-6-[N-(3′-methylphenyl)dithiocarbamoyl]-s-triazines (4a–l) and 2,4-bis[N-(3′-methylphenyl)dithiocarbamoyl]-6-arylamino-s-triazines (7a–l) were synthesized by two different synthetic routes. In the first route (A), 2,4,6-tricholoro-s-triazine (1) was condensed with N-(3-methylphenyl)ammoniumdithiocarbamate to afford compounds 3 or 6, which on reaction with different aryl amines afforded compounds 4a–l or 7a–l. In the second route (B), condensation of 1 with different aryl amines yielded compounds 2a–l or 5a–l. On further treatment with N-(3-methylphenyl)ammoniumdithiocarbamate these afforded compounds 4a–l or 7a–l. The newly synthesized compounds 4a–l and 7a–l were characterized by elemental analyses, infrared (IR), and 1H nuclear magnetic resonance (NMR) spectroscopic investigation. All the products were evaluated for their antibacterial and antifungal activity.

Synthesis and antimicrobial evaluation of novel benzo[b]thiophenes comprising β-lactam nucleus

Synthesis, structural characterization, and biological activity studies of benzo[b]thiophene derivatives containing β-lactam nucleus are described. Cycloaddition of azomethines (4a–j) to in situ-generated ketenes from 2,4-dichlorophenoxyacetic acid, in the presence of triethylamine and benzenesulfonyl chloride afforded the title compounds (5a–j). The stereochemical course of reaction depends on both the substituents on the ketenes as well as on the imines. The mechanism for the formation of cis/trans derivative is presented.

A new synthetic approach and biological evaluation of novel phenothiazines bearing tert-butyl group

A new and facile synthetic route is proposed for the synthesis of some novel phenothiazines (5a–5g) based on the reaction of 2-amino substituted benzenethiols with p-tert-butyl phenol in good yield. The newly synthesized compounds were characterized by IR, 1H NMR and mass spectral studies. Their antimicrobial activities against three strains of bacteria: Bacillus subtilis, Bacillus megaterium, Escherichia coli, and two strains of fungi: Aspergillus niger and Aspergillus oryzae, were investigated.

Synthesis and evaluation of chalcone analogues and pyrimidines as cyclooxygenase (COX) inhibitors

A series of chalcone analogues was synthesized and used as precursor for the synthesis of novel series of pyrimidines. Both groups have been evaluated for their effects on the cyclooxygenases (COXs) that are imperative enzymes in the genesis of prostaglandin H2, which is an antecedent for the biosynthesis of prostaglandins, thromboxanes and prostacyclins. The results depicted that chalcones and pyrimidines are very active inhibitors according to the pattern of substitution. Compounds C4, C5, P4 and P5 with methoxylation and nitro substitutions showed best results to inhibit COX-2.