Ali A. El-Emam

Synthesis, Antimicrobial, and Anti-inflammatory Activities of Novel 5-(1-Adamantyl)-4-arylideneamino-3-mercapto-1,2,4- triazoles and Related Derivatives

The reaction of 5-(1-adamantyl)-4-amino-3-mercapto-1,2,4-triazole (5) with various aromatic aldehydes in ethanol or acetic acid yielded the corresponding 4-arylideneamino derivatives 6a–v. Treatment of the 4-(2,6-difluoro- and dichlorobenzylideneamino) derivatives 6o and 6q with 1-substituted piperazines, and formaldehyde solution in ethanol afforded good yields of the corresponding 5-(1-adamantyl)-4-(2,6-dihalobenzylideneamino-2-(4-substituted-1-piperazinylmethyl)-1,2,4-triazoline-3-thiones 7a–p. 5-(1-Adamantyl)-4-arylideneamino-2-(4-ethoxycarbonyl-1-piperidylmethyl)-1,2,4-triazoline-3-thiones 8a–n, were similarly prepared via the reaction of the corresponding arylideneamino derivative with ethyl 4-piperidinecarboxylate and formaldehyde solution in ethanol. Compounds 6a–v, 7a–p and 8a–n were tested for in vitro activities against a panel of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. Several derivatives showed good or moderate activities, particularly against the tested Gram-positive bacteria. In addition, the in vivo anti-inflammatory activity of 21 compounds was determined using the carrageenan-induced paw oedema method in rats. Compounds 7d, 7g, 7i, 7j, 7l, 8c, 8e and 8l showed good or moderate dose-dependent activity in this area.

Synthesis, antimicrobial and antiviral evaluation of certain thienopyrimidine derivatives

Summary A series of 2-substituted amino-3-aminocyclopenteno or cyclohexeno[ b ]thieno[2,3- d ]-3,4-dihydropyrimidin-4-ones has been synthesized by reacting the corresponding thioureido derivatives with hydrazine hydrate. The thienoprimidine analogues obtained were further used to prepare their arylideneamino, thienotriazolopyrimidine or 2-methylthienotriazolopyrimidine derivatives. The prepared compounds were screened for antimicrobial, antiviral and cytotoxic activity. Some of the tested compounds showed promising activity. Detailed syntheses and spectroscopic and biological data are reported.

Spectrophotometric determination of propranolol in formulations via oxidative coupling with 3-methylbenzothiazoline-2-one hydrazone

A simple spectrophotometric method has been developed for the determination of propranolol hydrochloride in pure as well as in dosage forms. The method is based on the oxidative coupling reaction with 3-methylbenzothiazoline-2-one hydrazone. A mixture of an acidic solution of the chromogenic agent and the drug upon treatment with ceric ammonium sulfate produces an orange color peaking at 496 nm. The absorbance-calibration plot was linear over the range 1-10 microg/ml with minimum detectability (S/N=2) of 0.1 microg/ml (3.38x10(-7) M). The molar absorbitivity was 3.195x10(3) l/M/cm with correlation coefficient (n=10) of 0.9999. The different experimental parameters affecting the development and stability of the color were carefully studied and optimized. The proposed method was applied successfully to the determination of propranolol in its dosage forms. A proposal of the reaction pathway was presented.

Synthesis of novel 6-phenyl-2,4-disubstituted pyrimidine-5-carbonitriles as potential antimicrobial agents

New series of 6-phenyl-2,4-disubstituted pyrimidine-5-carbonitriles namely, 2-substitued thio-6-phenyl-3,4-dihydro-4-oxopyrimidine-5-carbonitriles (5a-d, 6, 7a-d, 8), 2-(4-chlorobenzylthio)-4-chloro-6-phenylpyrimidine-5-carbonitrile (9), 2-(4-chlorobenzylthio)-4-arylthio-6-phenylpyrimidine-5-carbonitriles (10a-d) and 2-(4-chlorobenzylthio)-4-arylamino-6-phenylpyrimidine-5-carbonitriles (11a-d) was synthesized and tested for in vitro activities against a panel of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. Compounds 5b, 5c, 6, 7a, 7b, 7c, 9 and 11a displayed marked antibacterial activity particularly against the tested Gram-positive bacteria, while compounds 6, 7c, 7d and 9 were moderately or weakly active against C. albicans.

FT-IR, FT-Raman, molecular structure, first order hyperpolarizability, HOMO and LUMO analysis, MEP and NBO analysis of 3-(adamantan-1-yl)-4-(prop-2-en-1-yl)-1H-1,2,4-triazole-5(4H)-thione, a potential bioactive agent

The optimized molecular structure, vibrational frequencies, corresponding vibrational assignments of 3-(adamantan-1-yl)-4-(prop-2-en-1-yl)-1H-1,2,4-triazole-5(4H)-thione have been investigated experimentally and theoretically using Gaussian09 software package. Potential energy distribution of normal modes vibrations was done using GAR2PED program. The HOMO and LUMO analysis are used to determine the charge transfer within the molecule. The stability of the molecule arising from hyperconjugative interaction and charge delocalization has been analyzed using NBO analysis. The calculated geometrical parameters are in agreement with the XRD data. The calculated first hyperpolarizability is high and the title compound is an attractive candidate for further studies in nonlinear optical applications. To estimate the chemical reactivity of the molecule, the molecular electrostatic potential is calculated for the optimized geometry of the molecule.

Synthesis of Novel Uracil Non‐Nucleoside Derivatives as Potential Reverse Transcriptase Inhibitors of HIV‐1

Novel emivirine and TNK‐651 analogues 5a–d were synthesized by reaction of chloromethyl ethyl ether and / or benzyl chloromethyl ether, respectively, with uracils having 5‐ethyl and 6‐(4‐methylbenzyl) or 6‐(3,4‐dimethoxybenzyl) substituents. A series of new uracil non‐nucleosides substituted at N‐1 with cyclopropylmethyloxymethyl 9a–d, 2‐phenylethyloxymethyl 9e–h, and 3‐phenylprop‐1‐yloxymethyl 9i–l were prepared on treatment of the corresponding uracils with the appropriate acetals 8a–c. Some of the tested compounds showed good activity against HIV‐1 wild type. Among them, 1‐cyclopropylmethyloxymethyl‐5‐ethyl‐6‐(3,5‐dimethylbenzyl)uracil 9c and 5‐ethyl‐6‐(3,5‐dimethylbenzyl)‐1‐(2‐phenylethyloxymethyl)uracil 9g showed inhibitory potency equally to emivirine against HIV‐1 wild type. Furthermore, compounds 9c and 9g showed marginal better activity against NNRTI resistant mutants than emivirine.

3-(1-Adamant­yl)-1-{[4-(2-meth­oxy­phen­yl)piperazin-1-yl]meth­yl}-4-methyl-1H-1,2,4-triazole-5(4H)-thione

The title compound, C25H35N5OS, is a functionalized triazoline-3-thione with substituted piperazine and adamantyl substituents attached at the 2- and 5-positions, respectively, of a triazole spacer with an approximately C-shaped conformation of the molecule. The piperazine ring adopts a chair conformation.

Spectroscopic investigation (FT-IR and FT-Raman), vibrational assignments, HOMO-LUMO analysis and molecular docking study of 2-(Adamantan-1-yl)-5-(4-nitrophenyl)-1,3,4-oxadiazole.

FT-IR and FT-Raman spectra of 2-(Adamantan-1-yl)-5-(4-nitrophenyl)-1,3,4-oxadiazole were recorded and analyzed. The vibrational wavenumbers were computed using DFT quantum chemical calculations. The data obtained from wavenumber calculations are used to assign vibrational bands obtained experimentally. The energy barriers of the internal rotations about the C-C bonds connecting the oxadiazole to the adamantane and benzene rings are reported. The geometrical parameters (DFT) of the title compound are in agreement with the XRD results. The calculated HOMO and LUMO energies allow the calculations of atomic and molecular properties and they also showed that charge transfer occurs in the molecule. A detailed molecular picture of the title compound and its interactions were obtained from NBO analysis. As can be seen from the MEP map of the title compound, which regions having the negative potential are over the electro negative atoms, the region having the positive potential are over the phenyl and adamantine rings and the remaining species are surrounded by zero potential. The molecular docking studies reveal that the adamantyl derivative may exhibit C-South African HIV-proteas inhibitory activity.

Synthesis, antimicrobial, and anti-inflammatory activity, of novel S -substituted and N -substituted 5-(1-adamantyl)-1,2,4-triazole-3-thiols

The reaction of 5-(1-adamantyl)-4-phenyl-1,2,4-triazoline-3-thione (compound 5) with formaldehyde and 1-substituted piperazines yielded the corresponding N-Mannich bases 6a–f. The reaction of 5-(1-adamantyl)-4-methyl-1,2,4-triazoline-3-thione 8 with various 2-aminoethyl chloride yielded separable mixtures of the S-(2-aminoethyl) 9a–d and the N-(2-aminoethyl) 10a–d derivatives. The reaction of compound 5 with 1-bromo-2-methoxyethane, various aryl methyl halides, and ethyl bromoacetate solely yielded the S-substituted products 11, 12a–d, and 13. The new compounds were tested for activity against a panel of Gram-positive and Gram-negative bacteria and the pathogenic fungus Candida albicans. Compounds 6b, 6c, 6d, 6e, 6f, 10b, 10c, 10d, 12c, 12d, 12e, 13, and 14 displayed potent antibacterial activity. Meanwhile, compounds 13 and 14 produced good dose-dependent anti-inflammatory activity against carrageenan-induced paw edema in rats.

Triazoles and fused triazoles, III: Facile and efficient synthesis of 2,5-disubstituted-s-triazolo[3,4-b]-1,3,4-thiadiazoles

SummaryThe development of a facile and efficient method for the synthesis of 2,5-diaryl-s-triazolo[3,4-b]-1,3,4-thiadiazoles4 a–e from the corresponding 3-aryl-4-amino-5-mercapto-s-triazole (2), is described. 3-Aryl-4-arylideneamino-5-mercapto-s-triazoles (3 a–e) were cyclized to compounds4 a–e by heating in nitrobenzene for a few minutes.ZusammenfassungEs wird eine einfache und effiziente Synthese von 2,5-Diaryl-1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazolen (4 a–e) aus den entsprechenden 3-Aryl-4-amino-5-mercapto-1,2,4-triazolen (2) beschrieben. Die 3-Aryl-4-arylidenamino-5-mercapto-1,2,4-triazole (3 a–e) wurden mittels Erhitzen in Nitrobenzol zu den Verbindungen4 a–e cyclisiert.