A. Said

Analgesic, anticonvulsant and anti-inflammatory activities of some synthesized benzodiazipine, triazolopyrimidine and bis-imide derivatives

A series of diazipine, pyrimidine, fused triazolopyrimidine and imide derivatives were newly synthesized using 4-phenyl-but-3-en-2-one 1 as a starting material and compounds 2 and 9 are intermediates. Initially the acute toxicity of the compounds was assayed via the determination of their LD(50). All the compounds were interestingly less toxic than the reference drug. The pharmacological screening showed that many of these obtained compounds have good analgesic, anticonvulsant and anti-inflammatory activities comparable to Valdecoxib, Carbamazepine and Predensilone as reference drugs. Regarding the protection against Carrageenan induced edema, five compounds were found more potent than Prednisolone. On the other hand, in searching for COX-2 inhibitor, the inhibition of plasma PGE2 for the compounds were determined and four compounds were found more potent than Prednisolone. The detailed synthesis, spectroscopic data, pharmacological screening and acute toxicity LD(50) for the synthesized compounds were reported.

Synthesis of some fused heterocyclic systems and their nucleoside candidates

A series of pyridofuro compounds were synthesized from 4-(4-chlorophenyl)-1,2-dihydro-2-oxo-6-(thiophen-2-yl)pyridine-3-carbonitrile (1) as starting material. Alkylation of 1 with ethyl bromoacetate gave the corresponding ester 2, which was condensed with hydrazine hydrate to afford the corresponding acid hydrazide derivative 3. Thrope-Ziegler cyclization of 2 with sodium methoxide gave furo[2,3-b]pyridine derivative 4, which was reacted with thiosemicarbazide, allyl isothiocyanate, formamide or hydrazine hydrate to give furopyridine derivatives 5–8, respectively. The latter compound 8 was cyclized with acetylacetone or formic acid to give the corresponding compounds 9 and 10, respectively. Furthermore, sulfurization of 1 with P2S5 gave the corresponding thioxopyridine 11, which was reacted with glycosyl (or galactosyl) bromide, morpholine or piperidine to give the corresponding thioglycoside 12a,b and Mannich base 14a,b derivatives. The deacetylation of 12a,b gave the corresponding deacetylated thioglycosides 13a,b, respectively. All the newly synthesized compounds were characterized by the elemental analyses and spectroscopic evidences (IR, 1H- and 13C NMR).

Synthesis and antimicrobial activities of some newly 2,4,6-tri-substituted pyridine derivatives

A series of novel 2-(2-(substituted benzylidene)hydrazinyl)-N′-(substituted benzylidene)-6-chloropyridine-4-carbohydrazide (5a–e), 2-(2-cycloalkylidenehydrazinyl)-6-chloro-N’-cyclo-alkylidenepyridine-4-carbohydrazide (6a,b), 2-(2-(1-(4-substituted phenyl)ethylidene)hydrazinyl)-6-chloro-N′-(1-(4-substituted phenyl)ethylidene)pyridine-4-carbohydrazide (7a,b) and 2-(2-(1-(pyridinyl)ethylidene)hydrazinyl)-6-chloro-N′-(1-(pyridinyl) ethylidene)pyridine-4-carbo-hydrazide (8a–c) derivatives have been synthesized by treating treating 2-chloro-6-hydrazinoisonicotinic acid hydrazide 4 with selected active reagents. Their structures were confirmed by spectral and analytical data. The synthesized compounds were investigated for antimicrobial activities. The antimicrobial screening showed that many of these obtained compounds have good activities comparable to Streptomycin and Fusidic acid as reference drugs.

Synthesis and Biological Activity of Some Nucleoside Analogs of Hydroquinoline-3-Carbonitrile

Hydroquinoline acyclonucleosides 2, 4, 6a,b, 8a,b, 9a,b, and their corresponding N-alkyl derivatives (10–12) were obtained by the reaction of 1a,b with acetoxybutylbromide, (2-acetoxyethoxy)methyl bromide, 3-chloropropanol, 1,3-dichloro-2-propanol, epichlorohydrin, propargyl/allyl bromides in the presence of K2CO3 in dry dimethylformamide (DMF). In a similar manner, reaction of 1a,b with glycosyl/galactosyl and lactosyl bromide afforded the corresponding N-nucloside derivatives 13a,b, 15a,b, and 17, respectively. Deacetylation of the N-nucleosides derivatives in the presence of Et3N/MeOH and few drops of water gave the deprotected derivatives 3, 5, 7a,b, 14a,b, 16a,b, and 18 in good yields, respectively. All the newly synthesized compounds are elucidated by infrared, 1H, 13C NMR and elemental analyses. Some of these compounds were screened for antimicrobial activities.

Synthesis of a novel series of pyrimido- and triazino[4,5- b ] quinolines

New tetrahydropyrimido[4,5-b]quinolines, hexahydropyrimido[4,5-b]quinolines, a thioxohexahydropyrimido[4,5-b] quinoline, an octahydropyrimido[4,5-b]quinoline and a tetrahydro[1,2,3]triazino[4,5-b]quinoline have been synthesised. A series of S-alkyltetrahydroprimido[4,5-b]quinolines was obtained by the reaction of the thioxohexahydropy-rimido[4,5-b]quinoline with allyl bromide, propargyl bromide or with epichlorohydrin. All newly synthesised compounds were characterised by IR, 1H, 13C NMR and elemental analysis.

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.

Chemistry of 4,6-diaryl(heteroaryl)-2-oxonicotinonitriles and their fused heterocyclic systems

Abstract This review describes and analyzes the different reported synthetic methods of 4,6-diaryl-2-oxonicotinonitriles, in addition to their importance as building blocks for the synthesis of bi-, tri-, tetra-, and pentacyclic pyridine derivatives with pharmaceutical interest. Graphical Abstract