Omar A. Al-Deeb

Synthesis, analgesic and anti-inflammatory evaluation of some novel quinazoline derivatives

Two series of some new 2,4,6-trisubstituted-quinazoline derivatives were prepared and screened for their analgesic, anti-inflammatory activity and acute toxicity. Four compounds were more potent analgesic agents than the reference drug Indomethacin and thirteen compounds showed significant anti-inflammatory activity. Seven compounds showed combined ability to inhibit both pain and inflammation. Compounds tested for acute toxicity showed no toxic symptoms or mortality rates 24 h post-administration implying their good safety margin.

Synthesis of 4-alkyl (aryl)-6-aryl-3-cyano-2(1H)-pyridinones and their 2-imino isosteres as nonsteroidal cardiotonic agents

Thirty new 1,2-dihydropyridine derivatives of the general formula 4-alkyl (aryl)-6-aryl-3-cyano-2(1H)-pyridinones (1-15) and 4-alkyl (aryl)-6-aryl-3-cyano-2(1H)-iminopyridines (16-30) were synthesized using one-pot multicomponent reactions of the properly substituted acetophenone, appropriate aldehyde, ammonium acetate and ethyl cyanoacetate (1-15) or malononitrile (16-30) in ethanol. These target compounds (1-30) were evaluated for their cardiotonic activity using the spontaneously beating atria model, from reserpine-treated guinea pigs. The best pharmacological profile was obtained with 3-cyano-6-(3,4-dimethoxyphenyl)-4-(4-hydroxyphenyl)-2(1H)-pyridinone (9) which displaced selectivity for increasing the force of contraction (108.7 +/- 6.7,% change over control) rather than the frequency rate (40.8 +/- 5.3,% change over control) at a 5 x 10(-4) M concentration. The effects of structural changes upon activity are reported.

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.

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.

Voltammetric determination of N-nitrosoderivatives of atenolol and propranolol in simulated gastric juice.

A highly sensitive and simple voltammetric method is proposed for the determination of N-nitrosoatenolol (NA) and N-nitrosopropranolol (NP) in simulated gastric juice. The method is based on measuring the differential-pulse polarographic peak produced by NA and NP in Britton-Robinson buffers of pH 3 and 4 for NA and NP, respectively. Both compounds yielded diffusion-controlled current with diffusion-current constants of 7.23 +/- 0.03 and 9.46 +/- 0.06 for NA and NP, respectively. The current-concentration plots were rectilinear over the range 0.16-9.6 micrograms ml-1 with minimum detectability (S/N = 2) of 0.015 microgram ml-1 (5 x 10(-8) M) for NA; for NP the range was 0.08-8.0 micrograms ml-1 with minimum detectability (S/N = 2) of 0.009 microgram ml-1 (3 x 10(-8) M). The proposed method was successfully applied to study the possible in vivo production of the nitroso-derivatives under the standard nitrosation reaction conditions recommended by WHO. The method is characterized by simplicity and higher sensitivity as compared with the reported HPLC method.

Experimental FT-IR, Laser-Raman and DFT spectroscopic analysis of a potential chemotherapeutic agent 6-(2-methylpropyl)-4-oxo-2-sulfanylidene-1,2,3,4-tetrahydropyrimidine-5-carbonitrile

In this study, the experimental and theoretical vibrational frequencies of a newly synthesized potential chemotherapeutic agent namely, 6-(2-methylpropyl)-4-oxo-2-sulfanylidene-1,2,3,4-tetrahydropyrimidine-5-carbonitrile have been investigated. The experimental FT-IR (4000-400 cm(-1)) and Laser-Raman spectra (4000-100 cm(-1)) of the molecule in solid phase have been recorded. The theoretical vibrational frequencies and optimized geometric parameters (bond lengths and bond angles) have been calculated by using density functional theory (DFT/B3LYP: Becke, 3-parameter, Lee-Yang-Parr) and M06-2X (the highly parametrized, empirical exchange correlation function) quantum chemical methods with 6-311++G(d,p) basis set by Gaussian 09 W software, for the first time. The assignments of the vibrational frequencies have been done by potential energy distribution (PED) analysis by using VEDA 4 software. The theoretical optimized geometric parameters and vibrational frequencies have been found to be in good agreement with the corresponding experimental data, and with the results in the literature. In addition, the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) energies and the other related molecular energy values have been calculated and depicted.

Synthesis of novel uracil non-nucleosides analogues of 3,4-dihydro-2-alkylthio-6-benzyl-4-oxopyrimidines and 6 -benzyl -1 -ethoxymethyl -5 -isopropyluracil

A series of new uracil non-nucleosides analogues of S-DABOs was synthesised by reaction of 5-alkyl-6-(p-chlorobenzyl)-2-thiouracils with chloroethyl dialkylamine hydrochloride, N-(2-chloroethyl)-pyrrolidine hydrochloride, N-(2-chloroethyl)-piperidine hydrochloride or appropriate haloethers. Novel emivirine analogues were synthesised by silylation of 5-alkyl-6-(p-chlorobenzyl)uracils and treatment with bromomethyl methyl ether, chloromethyl ethyl ether or benzyl chloromethyl ether. Compounds 6-(p-chlorobenzyl)-5-ethyl-1-ethyloxymethyluracil (9e) and 1-benzyloxymethyl-6-(4-chlorobenzyl)-5-ethyluracil (9f) showed activity against wild-type HIV-1 strain III B in MT-4 cells.

Synthesis and Antimicrobial Activity of Some Novel 5-Alkyl-6-Substituted Uracils and Related Derivatives

6-Chloro-5-ethyl-, n-propyl- and isopropyluracils 5a-c were efficiently prepared from the corresponding 5-alkybarbituric acids 3a-cvia treatment with phosphorus oxychloride and N,N-dimethylaniline to yield the corresponding 5-alkyl-2,4,6-trichloro-pyrimidines 4a-c, which were selectively hydrolyzed by heating in 10% aqueous sodium hydroxide for 30 minutes. The reaction of compounds 5a-c with 1-substituted piperazines yielded the corresponding 5-alkyl-6-(4-substituted-1-piperazinyl)uracils 6a-j. The target 8-alkyltetrazolo[1,5-f]pyrimidine-5,7(3H,6H)-diones 7a-c were prepared via the reaction of 5a-c with sodium azide. Compounds 6a-j and 7a-c were tested for in vitro activities against a panel of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. Compound 6h displayed potent broad-spectrum antibacterial activity, while compound 6b showed moderate activity against the Gram-positive bacteria. All the tested compounds were practically inactive against Candida albicans.

Stability-indicating liquid chromatographic determination of trifluoperazine hydrochloride in bulk form and tablets

Abstract A selective high-performance liquid chromatographic procedure for the stability-indicating determination of trifluoperazine hydrochloride in the presence of its photolytic degradation products is demonstrated. The liquid chromatographic separation was achieved isocratically on a MicroPak™ NH 2 -10 column (10 μm, 30 cm×4 mm φ) utilizing a mobile phase containing acetonitrile, tetrabutylammonium hydroxide (TBAH) and o -phosphoric acid (50.5:0.83:0.1, made up to 100 ml with water, v/w/w, pH 6.5) at a rate of 1 ml min -1 with UV-detection (254 nm) at ambient temperature. Complete resolution of the unchanged trifluoperazine from its photodegradates could be achieved. Satisfactory results were obtained for drug assay and recovery testing.

Vibrational spectra, NBO analysis, HOMO-LUMO and first hyperpolarizability of 2-{[(2-Methylprop-2-en-1-yl)oxy]methyl}-6-phenyl-2,3,4,5-tetrahydro-1,2,4-triazine-3,5-dione, a potential chemotherapeutic agent based on density functional theory calculations.

The experimental FT-IR and FT-Raman spectra of 2-{[(2-Methylprop-2-en-1-yl)oxy]methyl}-6-phenyl-2,3,4,5-tetrahydro-1,2,4-triazine-3,5-dione were recorded. The optimized geometric parameters, normal mode frequencies and corresponding vibrational assignments of the compound have been examined by means of density functional theory. Reliable vibrational assignments and molecular orbital have been investigated by the potential energy distribution and natural bonding orbital analyses, respectively. The calculated first hyperpolarizability of the title compound is 2.82×10(-30) esu which is 21.69 times that of the standard NLO material urea. MEP was performed by the B3LYP level and the predicted infrared intensities and Raman activities have also been reported. Quantum chemical parameters were arrived from the frontier molecular orbital theory. The calculated geometrical parameters are in agreement with experimental results. From the MEP it is evident that the negative charge covers the CO groups and the positive region is over the rings and NH group.