Mohamed A. Moustafa

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.

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.

Synthesis of certain uracil-6-yl or tetrazol-5-ylpyrazolin-5-one and pyrazole derivatives as potential anti-inflammatory agents

Certain pyrazolin-5-one and pyrazole derivatives bearing uracil-6-yl or tetrazol-5-yl moiety in position 1 have been synthesized. The anti-inflammatory activity of six representative compounds have been tested and the results are reported.

Synthesis of piperazino and morpholino derivatives of aryloxypropane with potential analgesic and possible antimigraine activities

Modeling studies demonstrate that aryl piperazines (I), aryloxyalkylamines (II), phenylalkykamines (III) and indolylalkylamines (VI) may interact at 5-HT receptors in a similar manner. Examination of these structures (I–VI) reveals that all possess an aromatic moiety and terminal amine binding sites (Glennon et al., J Med Chem 32(8):1921–1926, 1989). In the present investigation a new series of aryloxyalkylamines (4, 5, 8, and 9) was designed and synthesized, in which the aromatic moiety is a phenyl group substituted at the 2,3-, 2,4-, 2,5-, or 2,6-positions by halogens and the terminal amine is N-methylpiperazine, or morpholine. In addition, the alkyl side chain is ethyl, or substituted ethyl at the α- or β-carbon by a methyl group. The length of the alkyl chain that separates the terminal amine from the ether oxygen atom of the aryloxy group is of major importance, and two-carbon chain appears optimal. The structures of the new compounds were assessed by microanalyses, IR, and NMR. The analgesic activity of selected compounds was performed on experimental animals and proved to be in the range of 85–100% relative to aspirin.Graphical Abstract

Percentages of the deuterium retained afterpara-hydroxylation of (R) (+) 4-2H-phenytoin and (S) (−) 4-2H-phenytoin in rat

Abstract(R) (+) and (S) (−) 4-2H-phenytoin have been used as substrates for the determination of the percentage of deuterium retention (NIH shift) afterpara-hydroxylation of the substrates in rat. By using GC-MS analyses, the percentages of deuterium retention were found to be 69% and 70% for the (R) and (S) phenyl rings, respectively. The results add additional evidence for the involvement of arene oxide in the oxidation of thepro (R) andpro (S) phenyls of phenytoin. The oxidation process of each ring could be mediated by independent enzyme systems, a rapid oxidative enzyme for thepro (S) phenyl and a slow oxidative enzyme for thepro (R) phenyl.

Synthesis of aryloxyalkylamines as h5-HT1B agonists with potential analgesic activity

Most h5-HT1B serotonin subreceptors agonists bind with high affinity but low selectivity. Aryloxyalkylamines are a curious exception. In this investigation a new series of aryloxyalkylamines (4–7, 10, 11) was designed and synthesized in which the naphthyl moiety in propranolol (I) is replaced by substituted phenyl group; in addition the alkyl side-chain is ethyl or α-substituted ethyl, thus keeping the distance between O and N atoms unchanged from the case of II. For a number of the synthesized compounds the binding affinity at 5-HT1B and 5-HT1D was determined and some were found to bind with high affinity and selectivity compared with I, and with comparable affinity and selectivity to II. Analgesic activity of selected synthesized compounds was investigated on experimental animals and proved to be 66–100% that of aspirin.