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ABSTRACT: Twenty 3,5-disubstituted isoxazoles have been synthesized and tested against fourth instar Aedes aegypti larvae. In the synthesis of title compounds, modifications have been made in the C-5 side-chain with a view to test their larvicidal activity. These isoxazoles have been obtained by 1,3-dipolar cycloaddition of arylnitrile oxides to terminal alkynes which furnished the desired products in 20% to 79% yields. A comparative study of the larvicidal activity between 3-(3-aryl-isoxazol-5-yl)-propan-1-ols and 3-(3-aryl-isoxazol-5-yl)-propionic acids clearly demonstrated that the latter compounds possess much better larvicidal activity than the former. We also tested two esters, viz., methyl 3-[3-(phenyl)-isoxazole-5-yl] propionate and methyl 3-[3-(4-chlorophenyl)-isoxazole-5-yl] propionate, where the latter presented an excellent larvicidal profile.
Bioorganic & medicinal chemistry 12/2012; · 2.82 Impact Factor
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ABSTRACT: AbstractA simple and easy synthesis of ten arylamidoximes from arylnitriles and hydroxylamine is described. The formation of the arylamides
has been observed to a much lesser extent in the present work. A new mechanism for the formation of arylamidoximes, as well
as arylamides, from arylnitriles and hydroxylamine is suggested. Quantum mechanical calculations have been carried out to
support this mechanism. The enthalpy of formation in conjunction with atomic charges of the reactants and intermediates helped
to understand more about the generation of the products.
Graphical Abstract
Monatshefte fuer Chemie/Chemical Monthly 05/2012; 140(11):1319-1324. · 1.53 Impact Factor
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ABSTRACT: In this study, the antinociceptive properties of 3,4-dihydro-2,6-diaryl-4-oxo-pyrimidine-5-carbonitrile derivatives 5a-i at doses of 25 and 50 mg/kg were evaluated in mice, using the abdominal constriction test. Molecular modeling studies were also performed using density functional theory calculations. These data provided information about the electrostatic and ionization potentials and were used to compare the antinociceptive activity of the title compounds. The most active compounds were 3,4-dihydro-2-(4-chlorophenyl)-6-(4-methoxyphenyl)-4-oxo-pyrimidine-5-carbonitrile (5b) and 3,4-dihydro-2,6-diphenyl-4-oxo-pyrimidine-5-carbonitrile (5i), which inhibited the number of abdominal constrictions, at 50 mg/kg dose, in 88.6% and 88% of the sample, respectively. A preliminary SAR study demonstrated that halogen replacement in the phenyl rings of the compounds under study reduces the antinociceptive activity. DFT calculations showed that there is a high correlation between the ionization potentials and the analgesic properties of the compounds. It was found that compounds with a positive ionization potential (compounds 5b and 5i) were found to be the best analgesic drugs in this series.
Molecules 01/2012; 17(1):809-19. · 2.39 Impact Factor
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ABSTRACT: 1,2,3-Triazoles have been extensively studied as compounds possessing important biological activities. In this work, we describe the synthesis of ten 2-(1-aryl-1H-1,2,3-triazol-4-yl)propan-2-ols via copper catalyzed azide alkyne cycloaddition (CuAAc or click chemistry). Next the in vitro antifungal activity of these ten compounds was evaluated using the microdilution broth method against 42 isolates of four different Candida species. Among all tested compounds, the halogen substituted triazole 2-[1-(4-chlorophenyl)-1H-(1,2,3)triazol-4-yl]propan-2-ol, revealed the best antifungal profile, showing that further modifications could be done in the structure to obtain a better drug candidate in the future.
Molecules 01/2012; 17(5):5882-92. · 2.39 Impact Factor
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ABSTRACT: The convergent synthesis of an unusual (but simple) class of compounds 5a-g has been achieved by the copper-catalyzed [3+2] cycloaddition reaction of 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl azide 4 with propynyl 3-[3-(aryl)-1,2,4-oxadiazol-5-yl] propionates 3a-g. The formerly known azide 4 has been prepared according to the literature procedure; however, the synthesis of esters 3a-g is being reported for the first time. The infrared as well as (1)H NMR spectra of all new products are in agreement with their proposed structures. By carrying out the nOe experiment of one of the final compounds 5a, we have been able to establish that only the 1,4-regioisomers have been formed in the cycloaddition reaction. All final products presented weak cytotoxic activity, but 5e and 5g had somewhat better behaviour showing 22-25% cell growth inhibition against two cell strains: NCI-H(292) (lung carcinoma) and HEp-2 (larynx carcinoma).
European journal of medicinal chemistry 04/2009; 44(9):3571-6. · 3.27 Impact Factor
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ABSTRACT: The synthesis of four different types of oxadiazoles containing a terminal acetylenic group is described. Reaction of these oxadiazoles with various azidoglycosides via a copper-catalyzed [3+2] cycloaddition ('click chemistry') afforded the corresponding glycosyl-triazole linked 1,2,4-oxadiazoles in good yields.
Carbohydrate Research 12/2007; 342(16):2440-9. · 2.33 Impact Factor
