Mohamed M. Baraka

Synthesis and antiviral activity of new pyrazole and thiazole derivatives

New N-acetyl (5-8) and N-thiocarbamoyl (9-12) derivatives of 4,5-dihydropyrazole were synthesized starting from alpha,beta-unsaturated ketones under the effect of hydrazine hydrate and thiosemicarbazide, respectively. N-Thiocarbamoylpyrazole derivatives (9-12) were cyclized using either ethyl bromoacetate or phenacyl bromides to afford the novel pyrazolothiazol-4(5H)-ones (13-16) or pyrazolothiazoles (17-24). The antiviral activity for such novel compounds against a broad panel of viruses in different cell cultures revealed that N-acetyl 4,5-dihydropyrazole 7 was the only active one at subtoxic concentrations against vaccinia virus (Lederle strain) in HEL cell cultures with a 50% effective concentration (EC(50)) value of 7 microg/ml.

Spectrophotometric method for the determination of flufenamic and mefenamic acids

A spectrophotometric method was developed for the determination of flufenamic and mefenamic acids both in the pure form and in pharmaceutical dosage forms. The method depends on their complexation with copper(II) ammine sulphate. The complex is extracted with chloroform and treated with diethyldithiocarbamate solution, whereupon another copper(II) complex (λmax. 430 nm) is formed. Beers law is followed over the concentration ranges 6–60 µg ml–1 for flufenamic acid and 6–48 µg ml–1 for mefenamic acid.

Synthesis of new benzotriazepin-5(2H)-one derivatives of expected antipsychotic activity

A new series of 3,4-dihydro-1H-benzo[e][1,2,4]triazepin-5(2H)-one derivatives were synthesized by cyclocondensation of benzohydrazides (II, IX), derived from the reaction of N-methyl-isatoic anhydride with phenyl hydrazine and isonicotinic acid hydrazide, respectively, with formaldehyde, aromatic aldehydes in acidic medium or with carbon disulfide in alkaline medium, the last reaction was only carried out with benzohydrazide II. Benzotriazepinone derivatives IV,Va–h,VI, and XI were subjected to ptosis test using clozapine as a reference drug to evaluate their antipsychotic activity. It was found that 2-thioxobenzotriazepinone VI had the same antipsychotic activity as reference drug clozapine but with lesser side effects whereas it showed nonsignificant CNS depressant activity upon using forced swim pool test as well as no neurotoxicity when tested in mice using rotarod or horizontal screen tests.Graphical AbstractA new series of benzotriazepin-5(2H)-ones (IV,Va–h, VI, and XI) were prepared starting from isatoic anhydride and their antipsychotic activity revealed that 2-thioxobenzotriazepinone VI was superior to the reference drug clozapine.

Synthesis of New 2,3‐Dihydroquinazolin‐4(1H)‐one Derivatives for Analgesic and Anti‐inflammatory Evaluation

Starting from isatoic anhydrides, several new 2,3‐dihydroquinazolin‐4(1H)‐one derivatives bearing chalcone or pyrazole or thiazole moieties at the third position were synthesized. The analgesic and anti‐inflammatory activities for most compounds were studied at a dose level of 50 mg/kg via the acetic‐acid‐induced writhing‐response method and carrageenan‐induced edema method, respectively. The study showed that the chalcones bearing a 4‐chlorophenyl group 4c or 4‐nitrophenyl group 4b were the most active ones as analgesics. Both chalcone 4c and N‐phenyl pyrazole bearing 4‐methoxy phenyl group 5b showed a higher anti‐inflammatory activity than celecoxib but still lower than that of diclofenac sodium. Moreover, the chalcone 4c has nearly the same ulcerogenic index as the selective cyclooxygenase‐2 inhibitor celecoxib.

Design, synthesis and preliminary antiviral screening of new N-phenylpyrazole and dihydroisoxazole derivatives

A new series of N-phenylpyrazoles and dihydroisoxazles was synthesized starting from α,β-unsaturated ketones in basic media using phenyl hydrazine and hydroxylamine HCl, respectively. Antiviral evaluation of the target compounds revealed that the dihydroisoxazole derivatives have promising antiviral activity against hepatitis A virus and herpes simplex virus type 1.

Synthesis, Anticonvulsant Activity, and SAR Study of Novel 4-Quinazolinone Derivatives: Anticonvulsant Quinazolinones

Series of N‐(4‐substitutedphenyl)‐4‐(1‐methyl (or 1,2‐dimethyl)‐4‐oxo‐1,2‐dihydroquinazolin‐3(4H)‐yl)‐alkanamides (5a–j) and 4‐chloro‐N′‐((1‐methyl (or 1,2‐dimethyl)‐4‐oxo‐1,2‐dihydroquinazolin‐3(4H)‐yl)‐alkaloyl)benzohydrazides (6a–f) were designed based on the previously reported essential structural features for anticonvulsant activity. Several amino acids were incorporated within the synthesized quinazolin‐4(3H)‐ones to improve their bioavailability and the anticonvulsant activity. Synthesis of the target compounds was accomplished in four steps starting from the reaction between N‐methyl isatoic anhydride and the appropriate amino acid. Then, the carboxylic acid group was utilized to synthesize the required final structures. The new quinazolinone derivatives were evaluated for their anticonvulsant activity according to the Anticonvulsant Drug Development (ADD) Program protocol. All the 16 new quinazolinones exhibited good anticonvulsant activity; especially 5f, 5b, and 5c showed superior anticonvulsant activities in comparison to the reference drug, with ED50 values of 28.90, 47.38, and 56.40 mg/kg, respectively.

Synthesis and Biological Evaluation of 2-Oxo/Thioxoquinoxaline and 2-Oxo/Thioxoquinoxaline-Based Nucleoside Analogues

ABSTRACT Several O- and S-quinoxaline glycosides have been prepared by glycosidation of 3-methyl-2-oxo(thioxo)-1,2-dihydroquinoxalines 1a,b with α-D-glucopyranosyl, α-D-galactopyranosyl, and α-D-lactosyl bromide in the presence of K2CO3 followed by deacetylation with Et3N/H2O. Furthermore, alkylation of 1a,b with 4-bromobutyl acetate, 2-acetoxyethoxymethyl bromide, and 3-chloropropanol afforded the corresponding O- and S-acycloquinoxaline nucleosides. Reaction of 1b with chloroacetic acid followed by condensation with sulfacetamide and sulfadiazine in the presence of Et3N/THF and ethyl chloroformate gave the corresponding sulfonamide derivatives 14 and 15, respectively. The structures of new compounds were confirmed by using IR, 1H, 13C NMR spectra and microanalysis. Some of these compounds were screened in vitro for antitumor and antifungal activities.