Remon M. Zaki

Synthesis and biological activity of pyrazolothienotetrahydroisoquinoline and [1,2,4]triazolo[3,4-a]thienotetrahydroisoquinoline derivatives

1-hydrazino-3-thioxo-5,6,7,8-tetrahydroisoquinoline-4-carbonitrile (3) was subjected to react with bifunctional compounds namely: acetylacetone, ethyl cyanoacetate, ethyl benzoylactate, diethylmalonate and ethyl acetoacetate to produce pyrazololthienotetrahydroisoquinoline derivatives 6-11. Also, heating of compound (3) with formic acid afforded triazolothienotetrahydroisoquinoline compound 5 which reacted with α-halogenated compounds to afford compounds 13a-e. Compound 13c when heated with triethylorthoformate afforded triazolo derivative 14. Also, compound 6 was used for synthesizing compounds 18-20. Representative compounds of the synthesized triazolo and pyrazolothienotetrahydroisoquinoline products were tested and evaluated as antimicrobial agents.

Synthesis and biological study of some new naphtho[2,1-b]furan and related heterocyclic systems

In the reaction of 1-cyano-2-naphthol (4) or its sodium salt with different alkylating agent, the O-alkylated derivatives (5a–d) were produced which underwent ring closure reactions using sodium ethoxide solution to give aminonaphtho [2,1-b]furan derivatives (6a–d). Ethyl 3-aminonaphtho[2,1-b]furan-2-carboxylate (8) was reacted with formamide to afford naphtho[1′,2′: 4,5]furo[3,2-d]pyrimidine (11) derivatives. The produced pyrimidino compound underwent various reactions to synthesise other heterocyclic compounds.

The biological activity of new thieno(2,3-c)pyrazole compounds as anti-oxidants against toxicity of 4-nonylphenol in Clarias gariepinus

Graphical abstract

Synthesis and antimicrobial activity of new heterocyclic compounds containing thieno[3,2-c]coumarin and pyrazolo[4,3-c]coumarin frameworks

Reaction of 4-chlorocoumarin-3-carbonitrile with ethyl thioglycolate and ethyl glycinate hydrochloride leads to a series of title products. Hydrazinolysis of amino thienocoumarin carboxylate afforded the hydrazino derivative which underwent various reactions to build new heterocyclic rings containing thienocoumarin moiety. Chloro acetylation of aminoester compound afforded the chloro acetyl amino which underwent nucleophilic substitution reactions with various amines. The following treatment with formaldehyde under Mannich conditions afforded the corresponding imidazo derivatives. Reaction of chloroacetylamino with potassium thiocyanate yielded ethylpyrimidothieno coumarin sulfanylacetate which was used as a versatile precursor for synthesis of other heterocycles. On the other hand, reaction of chloro coumarin carbonitrile with hydrazine gave the aminopyrazolocoumaine which reacted with bifunctionally compounds to give the substituted pyrimido derivatives. Diazotization and coupling of aminopyrazole with ethylcyanoacetate yielded ethylaminotriazinopyrazolocoumarine carboxylate. Several of the compounds obtained demonstrated considerable antifungal and antibacterial activity in the in vitro test systems.

Synthesis and antimicrobial activity of novel benzo[f]coumarin compounds

The acetyl benzo[f]coumarin condensed with phenyl hydrazine to afford the corresponding phenyl hydrazone which cyclized into the pyrazolyl benzocoumarin under Vilsmeier reaction conditions. The pyrazolylaldehyde was used as starting material for synthesis of other heterocyclic compounds containing pyrazolylbenzocoumarin moiety. The ethyl benzo[f]coumarin carboxylate were subjected to react with other reagents to synthesize thiazolidinyl and oxadiazolyl derivatives attached to benzocoumarin system. Some of novel synthesized compounds showed highly antibacterial and antifungal activities.

A convenient synthesis, reactions and biological studies of some novel selenolo[2,3-c]pyrazole compounds as antimicrobial and anti-inflammatory agents

Abstract5-Chloro-3-methyl-1-phenylpyrazole-4-carbonitrile 3 was reacted with selenium in the presence of sodium borohydride and chloroacetamide to afford selanyl acetamide 5, which underwent Thorpe–Ziegler cyclization upon heating with sodium ethoxide to give the novel synthesized 4-amino-3-methyl-1-phenyl-1H-selenolo[2,3-c]pyrazole-5-carboxamide compound (6). The latter compound was used as a versatile precursor for synthesis of other heterocyclic rings, namely pyrimidine, imidazopyrimidine and thiadiazinopyrimidine fused to selenolo[2,3-c]pyrazole moiety. The newly synthesized compounds and their derivatives were characterized by elemental and spectral analysis (IR, 1H NMR, 13C NMR and mass spectrometric analyses). Furthermore, some of these synthesized compounds were screened against various pathogenic bacterial and fungal strains. The results demonstrate that most of the synthesized compounds possess a significant antibacterial activity against gram-positive and gram-negative bacteria. Also, some of these compounds showed a remarkable antifungal activity, especially Candida albicans. On the other hand, some of the synthesized compounds possess high anti-inflammatory activity using carrageenan-induced rat paw edema assay compared with indomethacin.Graphical AbstractThe present work discussed synthesis of new selenolo[2,3-c]pyrazoles fused to other heterocyclic rings, namely pyrimidine, imidazopyrimidine and thiadiazinopyrimidine. Some of the synthesized compounds showed remarkable antibacterial, antifungal and anti-inflammatory activities.

A convenient synthesis and biological activity of novel thieno[2,3-c]pyrazole compounds as antimicrobial and anti-inflammatory agents.

A new method for synthesizing 4-amino-3-methyl-1-phenyl-1H-5-substituted thieno[2,3-c]pyrazole was reported. The substituted groups at position 5 include carbonitrile, carboxamide, N-phenyl carboxamide, and benzoyl groups. The newly synthesized compounds and their derivatives were characterized by elemental analysis and spectroscopy (IR, 1H NMR, and mass spectra). Furthermore, some of these synthesized compounds were screened against various pathogenic bacterial and fungal strains. The results demonstrate that most of the synthesized compounds possess a significant antibacterial activity against grampositive and gram-negative bacteria. In addition, most of these compounds showed a remarkable anti-fungal activity. On the other hand, some of the synthesized compounds possess high anti-inflammatory activity, which was demonstrated using the carrageenan-induced rat paw edema assay.

Reactions of 1-amino-5-morpholino-6,7,8,9-tetrahydrothieno[2,3-c] isoquinoline- 2-carbonitrile

1-Amino-5-morpholino-6,7,8,9-tetrahydrothieno[2,3-c]isoquinoline-2-carbonitrile has been converted to the chloro-acetylamino derivative which was subjected to nucleophilic substitution reactions with different amines. Reaction of 1-amino-5-morpholino-6,7,8,9-tetrahydrothieno[2,3-c]isoquinoline- 2-carbonitrile with triethyl orthoformate followed by cyclisation with hydrazine yielded an aminoiminopyrimidine derivative. The latter was used as a starting material for the synthesis of a variety of fused heterocyclic compounds which include triazolopyrimidothienotetrahydroiso-quinolines.

Efficient synthesis of some novel furo[3,2-e]pyrazolo[3,4-b]pyrazines and related heterocycles

ABSTRACT A series of novel 6-functionalized-5-amino-3-methyl-1-phenyl-1H-furo[3,2-e]pyrazolo[3,4-b]pyrazines (4a–c) was synthesized by the reaction of 3-methyl-6-oxo-1-phenyl-6,7-dihydro-1H-pyrazolo[3,4-b]pyrazine-5-carbonitrile (2) with α-halocarbonyl compounds such as: diethyl 2-bromomalonate, phenacyl bromide and chloroacetone. Cyclocondensation of the amino benzoyl 4b with diethyl malonate yielded the oxopyridine carboxylate derivative 5. Also, the starting intermediate amino ester compound 4a was allowed to react with ethanol amine to afford the hydroxyethyl caboxamide derivative 6. Furthermore, hydrazinolysis of the amino ester 4a afforded the corresponding amino carbohydrazide 7 which was used as a versatile precursor for synthesis of other heterocyclic compounds attached or fused to the furopyrazolopyrazine moiety. The chemical structures of the newly synthesized compounds were confirmed on the basis of elemental and spectral analyses containing FT-IR, 1H NMR, 13C NMR, and mass spectrometry hoping these molecules should allow us to investigate their pharmacological activities in the future study. GRAPHICAL ABSTRACT

A Convenient Synthesis, Reactions and Biological Activity of Some New 6H-Pyrazolo[4’,3’:4,5]thieno[3,2-d][1,2,3]triazine Compounds as Antibacterial, Anti-Fungal and Anti-Inflammatory Agents

We describe here the design and synthesis of novel pyrazolothienotriazine compounds based on diazotization followed by cycloaddition reactions of 4-amino-3-methyl-1-phenyl1H-thieno[2,3-c]pyrazol-5-carbonitrile with sodium nitrite in the presence of concentrated HCl in acetic acid. The produced chloropyrazolothienotriazine underwent nucleophilic substitution reactions with various primary and secondary amines including sulfa drugs to afford the N-substituted aminopyrazolothienotriazines. Hydrazinolysis of the chlorotriazine with hydrazine hydrate afforded the hydrazinotriazine, which was used as a versatile precursor for synthesis of other compounds. The chemical structures of the newly synthesized compounds were confirmed on the basis of elemental and spectral analyses containing Fourier transform infrared spectroscopy (FTIR), H and C nuclear magnetic resonance (NMR) and mass spectrometry. Some of the synthesized compounds showed high antibacterial and anti-fungal activities. Also, most of the tested compounds exhibited high anti-inflammatory activity compared with indomethacin using carrageenan induced rat paw edema assay.