Shaban M. Radwan

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 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 of Novel Thieno[2,3-c]pyridazinesand Related Heterocycles

Summary. The reaction of ethyl 2,3-dihydro-5,6-diphenyl-3-thioxopyridazine-4-carboxylate with ω-bromoacetophenones, chloro-N-arylacetamides, chloroacetonitrile, ethyl chloroacetate, or chloroacetone furnished the corresponding 4,5-diphenyl-3-hydroxy thieno [2,3-c]pyridazines. 2-Cyano-, 2-ethoxycabonyl-, and 2-acetyl-4,5-diphenyl-3-hydroxythieno[2,3-c]pyridazines were employed asprecursors in the synthesis of some novel furo [2′,3′:4,5]thieno[2,3-c]pyridazines, pyrano- [2′,3′:4,5]thieno[2,3-c]pyridazines, and thieno[2,3-c]pyridazines. The antibacterial and antifungal activities of some of the compounds are reported.Zusammenfassung. Die Reaktion von Ethyl-2,3-dihydro-5,6-diphenyl-3-thioxo-pyridazin-4- carboxylat mit ω-Bromacetophenon, Chlor-N-arylacetamiden, Chloracetonitril, Ethylchloracetat oder Chloraceton ergab die entsprechenden 4,5-Diphenyl-3-hydroxythieno[2,3-c]pyridazine. 2-Cyano-, 2-Ethoxycabonyl- und 2-Acetyl-4,5-diphenyl-3-hydroxythieno[2,3-c]pyridazine wurden als Vorläufer neuer Furo[2′,3′:4,5]thieno[2,3-c]pyridazine, Pyrano[2′,3′:4,5]thieno[2,3-c]pyridazine und Thieno[2,3-c]pyridazine eingesetzt. Die antibakteriellen und fungistatischen Eigenschaften einiger Verbindungen werden mitgeteilt.

SYNTHESIS AND SOME REACTIONS OF NEW BENZO[b]PYRAN DERIVATIVES

Abstract Reaction of cinnamonitriles 1a,b with 3-aminophenol (2a) or resorcinol (2b) gave the corresponding benzo[b] pyran derivatives (3a-d). Compound (3a) reacted with benzaldehyde to yield monobenzyli-dencamino derivative 4. Also, reaction of (3a) with benzenesulsulphonyl chloride gave 2-amino-3-cyano-4-phenyl-7-phenylsulphonylamido-4H-benzo[b]pyran (6) which, in turn, underwent some reactions to produce new benzo[b]pyrano[6,5-d]pyrimidine derivatives (7, 9) and (10).

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.

SYNTHESIS AND REACTIONS OF 2-CHLOROMETHYL-13-(2-FURYL)-3,4,11,12-TETRAHYDRO-4-OXOPYRIMIDO[4′,5′:4,5]THIENO[2,3-b]-BENZO[h]QUINOLINE

Abstract 3-Amino-2-carbamoyl-5,6-dihydro-4-(2-furyl)-thieno[2,3-b]-benzo[h]quinoline (3) was synthesized and allowed to react with chloroacetyl chloride to give N-chloroacetyl derivative 4. Cyclization of 4 into the title compound 5 was achieved in boiling acetic anhydride. Reactions of 5 with thiophenol, mor-pholine and/or thiourea afforded pyrimidinones 6, 7 and 8 respectively. Chlorination of 5 and 6 with phosphorus oxychloride gave the promising di- and monochloro derivatives (9 and 10) which were subjected for further reactions to produce other new pryrimido[4′,5′:4,5]thieno[2,3-b]-benzo[h]quinolincs 11–18.

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

Synthesis of some new imidazo[3 ,4 :1'2'] pyrimido[4',5':4,5]thieno[2,3-c] pyridazines and other fused thieno[2,3-c]pyridazines

5-Amino-3,4-diphenylthieno[2,3-c]pyridazine-6-carboxamide was prepared and used as starting material to form the novel 6-chloromethyl-3,4-diphenylpyrimido[4′,5′:4,5]thieno[2,3-c]pyridazin-8(7H)-one (3), the 6-(arylaminomethyl) compounds (4a–c), 7-aryl-7,8-dihydro-3,4-diphenylimidazo[3″,4″:1′,2′]pyrimido[4′,5′:4,5]thieno[2,3-c]pyridazin-10(6H)-ones (5a–c), ethyl 7,8-dihydro-8-oxopyrimido[4′,5′:4,5]thieno[2,3-c]pyridazine-6-acetate (6) and its carbohydrazide (7). The pyridazinothienopyrimidotriazepinedione 8, pyridothienopyridazine 12 and pyridazinothienooxazepine 13 were also prepared.

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.