Synthesis and Antituberculosis Activity of New Hydrazide Derivatives (original) (raw)
Related papers
Open Journal of Medicinal Chemistry, 2016
A series of substituted 2,7-dimethylimidazo[1,2-a]pyridine-3-carboxamides derivatives 5a-5m were synthesized through multi-step reactions. To achieve the synthesis of the desired compounds monobromo and dibromo substituted 2-amino-γ-picoline was reacted with ethyl 2-chloroacetoacetate. The crude ethyl ester subjected to hydrolysis in presence of lithium hydroxide to get 2a and 2b, with imidazo[1,2-a]pyridine-3-carboxylic acid to get 3a-3b, on treatment with substituted amines 4a-4g to get desired product 5a-5m in presence of EDCI and HOBt. The substituted imidazo[1,2-a]pyridine-3-carboxamides are characterized by FTIR, 1 H-NMR, 13 C-NMR and mass spectra. These newly synthesized compounds were tested in vitro for their antimycobacterial activity. The preliminary results of antituberculosis study showed that most of the synthesized compounds 5a-5m demonstrated moderate to good antituberculosis activity. Among the tested compounds 5b, 5d and 5e were found to be the most active with minimum inhibitory concentration (MIC) of 12.5 μg/mL against Mycobacterium tuberculosis (H37 RV strain) ATCC No-27294.
A series of imidazo[1,2-a]pyridine carboxamides (IPAs) bearing an N-(2-phenoxyethyl) moiety was designed and synthesized as new antitubercular agents. Seven 2,6-dimethyl IPAs demonstrated excellent in vitro activity (MIC: 0.025−0.054 μg/mL) against the drug susceptive H37Rv strain and two clinically isolated multidrug-resistant Mycobacterium tuberculosisstrains. Compound 10j displayed acceptable safety and pharmacokinetic properties, opening a new direction for further development. Figure 1. Design of the new molecules.
Synthesis and anti-mycobacterial evaluation of some pyrazine-2-carboxylic acid hydrazide derivatives
European Journal of Medicinal Chemistry, 2010
A series of pyrazine-2-carboxylic acid hydrazide derivatives were synthesized and screened for their activity against Mycobacterium tuberculosis. The results show that pyrazine-2-carboxylic acid hydrazide–hydrazone derivatives 3a–l were less active than pyrazinamide. In contrast, the N4-ethyl-N1-pyrazinoyl-thiosemicarbazide 4 showed the highest activity against M. tuberculosis H37Rv (IC90 = 16.87 μg/mL). Details of the structure–activity and structure–cytotoxicity relationships are discussed.
Turk. J. …, 2011
The difficulty in managing tuberculosis includes the prolonged duration of the treatment, the emergence of drug resistance, and coinfection with HIV/AIDS. Tuberculosis control requires new drugs that act on novel drug targets to help in combating resistant forms of Mycobacterium tuberculosis and reduce the treatment duration. For this purpose, 6-substituted-3(2 H) -pyridazinone-2-acetyl-2-(substituted/nonsubstituted acetophenone) hydrazone derivatives were synthesized and their structures were elucidated by elemental analyses, IR, and 1 H-NMR. The in vitro antimycobacterial activities of synthesized compounds 5a-l were determined by the agar proportion method against Mycobacterium tuberculosis H37Rv. Among the target compounds, 5b and 5f exhibited the best antimycobacterial activity, with a MIC value of 5 μ g/mL.
European journal of …, 2009
In the present investigation, a series of 1-isonicotinoyl-3-methyl-4-(2-(substitutedphenyl)hydrazono)-1H-pyrazol-5(H)-ones were synthesized by the reaction between isonicotinohydrazide with substituted ethylacetoacetate derivatives using acetic acid as solvent which yielded substituted pyrazol-5(H)-one derivatives. Newly synthesized compounds were tested for their in vitro anti-tubercular activity against Mycobacterium tuberculosis H37Rv using the BACTEC 460 radiometric system. Among the synthesized compounds, 4-(2-(2,6-dichlorophenyl)hydrazono)-1-isonicotinoyl-3-methyl-1H-pyrazol-5(4H)-one and 4-(2-(1-isonicotinoyl-3-methyl-5-oxo-1H-pyrazol-4(5H)-ylidene)hydrazinyl) benzene-sulfonamide were found to be more active agent against M. tuberculosis H37Rv with minimum inhibitory concentration of 0.0034, 0.0032 µM at actual MIC 1.66 and 1.64 µg/mL, respectively. Isonicotinohydrazide Pyrazol-5(H)-ones Anti-tubercular activity Anti-mycobacterial activity Mycobacterium tuberculosis M. tuberculosis H37Rv
Synthesis and Antimycobacterial Activity of a Novel Series of Isonicotinylhydrazide Derivatives
Archiv der Pharmazie, 2009
A series of eight N'-[(E)-(disubstituted-phenyl)methylidene]isonicotino-hydrazide derivatives were synthesized and evaluated for their in vitro antibacterial activity against Mycobacterium tuberculosis, and the activity expressed as the minimum inhibitory concentration (MIC) in µg/mL. Four compounds 2b-d and 2f exhibited a significant activity (0.6 µg/mL), when compared with first line drugs such as isoniazid (INH) and rifampin (RIP) and could be a good starting point to develop new lead compounds in the fight against multidrug resistant tuberculosis.
Antituberculosis: Synthesis and Antimycobacterial Activity of Novel Benzimidazole Derivatives
BioMed Research International, 2013
A total of seven novel benzimidazoles were synthesized by a 4-step reaction starting from 4-fluoro-3-nitrobenzoic acid under relatively mild reaction conditions. The synthesized compounds were screened for their antimycobacterial activity against M. tuberculosis H 37 Rv (MTB-H 37 Rv) and INH-resistant M. tuberculosis (INHR-MTB) strains using agar dilution method. Three of them displayed good activity with MIC of less than 0.2 M. Compound ethyl 1-(2-(4-(4-(ethoxycarbonyl)-2-aminophenyl)piperazin-1yl)ethyl)-2-(4-(5-(4-fluorophenyl)pyridin-3-ylphenyl-1H-benzo[d]imidazole-5-carboxylate (5g) was found to be the most active with MIC of 0.112 M against MTB-H 37 Rv and 6.12 M against INHR-MTB, respectively.