M. S. A. El-Gaby

Synthesis and biological evaluation of some novel thiazole compounds as potential anti-inflammatory agents

In the present investigation, furo[2,3-d]thiazol-5(2H)-one 5 was obtained from reaction of thiosemicarbazone derivative 2 with diethyl acetylene dicarboxylate. A series of newly synthesized 2-(hydrazinyl)thiazol-4(5H)-one 6, 7 &8 and 2-(4-(substituted)-thiazol-2-yl)hydrazono derivatives 9a, b &10 were synthesized from treatment of thiosemicarbazone derivative 2 with appropriate α-halogenated compounds. Also, a one pot synthesis of thiazole derivatives 13 &15 was achieved from three components reaction of hydrazone derivative 11 with phenyl isothiocyanate and α-halogenated compounds catalyzed by DMF/KOH. 4-(4-Morpholino phenyl) thiazol-2-amino 17 was obtained via the reaction of acetophenone derivative 1 with thiourea in presence of iodine. The reactivity of 2-aminothiazole 17 toward some electrophilic reagents was investigated. The structure of the newly compounds was confirmed on the basis of elemental analysis and spectral data. The antibacterial activity towards two Gram negative (Proteus mirabilis &Serratia marcesens) and two Gram positive (Staphylococcus aureus &Bacillus cereus) bacteria was investigated. The anti-inflammatory activity was also investigated and the inhibition of the carrageenin-induced oedema by these compounds was established.

Synthesis and Biological Activity of Some Novel Thieno[2,3-b]quinoline, Quinolino[3′,2′:4,5] thieno[3,2-d]pyrimidine and Pyrido[2′,3′:4,5] thieno[2,3-b]quinoline Derivatives

Thieno [2,3-b] quinoline derivative 5 was synthesized by the cycloalkylation of compound bi 3a with chloro acetonitrile. Interaction of compound 5 with formic acid, formamide, and thioacetamide furnished the corresponding quinolino[3′,2′:4,5]thieno[3,2- d]pyrimidine derivatives 7 , 8 , and 9 , respectively. Also, quinolinothienopyrimidine 11 was obtained in good yield by cyclization of compound 5 with phenyl isothiocyanate under reflux in pyridine. Triethyl orthoformate reacted with compound 5 to form the ethoxymethylene derivative 12 . Refluxing of 5 with acetic anhydride for a short time afforded acetamide derivative 16 , whereas when refluxed for a long time furnished the diacetyl derivative 17 . Fusion of compound 5 with urea and thiourea yielded the corresponding quinolinothienopyrimidines 19 and 20 , respectively. When compound 5 was reacted with urea in the presence of sodium ethoxide, the corresponding ureado derivative 18 was obtained. Treatment of 5 with sulfuric acid at r.t. furnished the novel thienoquinoline 6 , while on heating gave the acid derivative 21 . Pyrido [2′,3′: 4,5]thieno [2,3- d] quinoline 23–25 were synthesized by the interaction of 5 with ethyl cyanoacetate, benzylidenemalononitrile, and acetaldehyde/malononitrile, respectively. On preliminary screening, compounds 22 and 25 exhibited in vitro growth that was inhibitory activity against Saccharomyces Cerevisiae when compared with the standard fungicide Mycostatine. The structure of the biologically active compounds 22 and 25 remain unchanged when exposed to gamma irradiation up to 40 KGy.

“NOVEL SYNTHESIS AND CYCLIZATION REACTIONS OF 3-AMINO-2-MERCAPTOPYRROLE DERIVATIVES”

Abstract Interaction of cyanothioformamides with chalcones gave 3-amino-2-mercaptopyrroles, which have the tautomeric structures (3-aminopyrroline-2-thiones and 3-iminopyrrolidine-2-thiones). The latter was reacted with chloroacetic acid, ethyl chloroacetate, chloroacetamide and 2,3-dichloro-l,4-naphthoquinone to give the corresponding pyrrolothiazines derivatives. On using phenylisocyanate or p-chlorobenzoyl chloride, the corresponding pyrrolothiazole derivatives could be isolated. Replacement of chalcones by maleimides furnished pyrrolopyrrolinediones.

SOME RING CLOSURE REACTIONS WITH CYANOTHIOFORMAMIDES: NEW ROUTE FOR THE SYNTHESIS OF (IMIDAZOLIDINE, OXAZOLIDINE & PYRROLINE)-IMINOTHIONES, BENZOTHIAZOLOQUINAZOLINONES AND IMIDAZOQUINOXALINES

Abstract Cyanothioformarnides were reacted with isocyanates, isothiocyanates, aldehydes, acetylenedicarboxylic acid and anthranilic acids to produce imidazolidines, oxazolidines pyrroline, quinazolinones and benzothiazoloquinazolinones, respectively. Interaction of imidazolidineimino(thiones and dithiones) with o-phenylenediamines gave rise to imidazoquinoxalines and imidazoquinoxalinethiones, respectively.

SOME CYCLIZATION REACTIONS WITH 4-THIOHYDANTOIN: SYNTHESIS OF SOME NOVEL THIOPYRANOIMIDAZOLES, THIENOIMIDAZOLES AND IMIDAZOQUINOLINES AND SOME METAL COMPLEXES WITH BIOLOGICAL INTEREST

Abstract 4-Thiohydantoin (II) with chloroacetic acid, chloroacetanilides and cyanothioformamides gave thieno[2,3-d)imidazoles (IV, V and IX), respectively. α,β-Unsaturated nitriles and anthranilic acids reacted with (II) to produce thiopyrano[2,3-d]imidazoles (III) and imidazo[4,5-b]quinolines (VII). Some metal complexes were prepared and the antimicrobial activity of some selected compounds was also reported.

A COMPARATIVE STUDY OF 4-THIOXO-(IMIDAZOLIDINES AND OXAZOLIDINES) AND SOME NUCLEOPHILIC REAGENTS

Abstract The imidazolidines (II) were reacted with amines, H2S and o-phenyhediamines to give 4-substituted imino derivatives (VI), thiohydantoin (VII) and 1-phenyl-3 -substituted-1H-imidazo[4,5-b]-quinoxaline-2-(3H)-ones(XIII), respectively. Interaction of the oxazolidines (V) with amines, o-phenylenediamines and o-aminophenol caused fission of the oxazole ring to produce (XIV, XVII & XIX) respectively.

Recent Trends in Chemistry of Thiazolopyridines

The aim of this review article is to present the syntheses, reactions, and applications of thiazolopyridines.

SYNTHESIS AND ANTIBACTERIAL ACTIVITY OF SOME NOVEL THIOUREA, NAPHTHO[2,3-d]THIAZOLE, QUINAZOLINE AND THIENO[2,3-d]PYRIMIDINE DERIVATIVES CONTAINING SULFONAMIDO MOIETIES

Abstract p-Substituted sulfamoylphenyl isothiocyanates 1a-d were prepared using reported procedures. The reactivity of 1a-d towards some nitrogen nucleophiles was investigated. Thus, interaction of 1 with aromatic amines and anthranilic acids furnished N1,N3-disubstituted thioureas 2a-c and 3-[4-N-substituted sulphonamido]phenyl-2-thioxo-4-(3H)-quinazolin-4-ones 4a-f, respectively. Alkylation of 4c with ethyl chloroacetate in acetone containing anhydrous potassium carbonate to yield quinazoline 5. Hydrazinolysis of 5 using ethanolic hydrazine hydrate afforded the corresponding acid hydrazide 6. Finally, treatment of 1a,b,d with 2-amind-3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophene yielded thieno[2,3-d]pyrimidines 10a-c bearing sulphonamido moieties. Structures of the new compounds were established by their elemental analyses and spectral data. Also, the most of these compounds were tested in vitro for their antimicrobial activity against some Gram positive and Gram negative bacteria.

Synthesis of Thiazolidine and Thiophene Derivatives for Evaluation as Anticancer Agents

The non-isolated adducts (3a,b) were used as key intermediates to synthesize some novel thiazolidine and thiophene derivatives. Compound (4) exhibited a remarkable antitumor activity against EAC cells compared with the Doxorubicin as a positive control.

STUDIES ON THIAZOLOPYRIDINES. PART 5: SYNTHESIS OF HITHERTO UNKNOWN THIAZOLINONE AND THIAZOLO[3,2-a]PYRIDINE DERIVATIVES HAVING IN THEIR STRUCTURE THE MORPHOLIN-4-YL MOIETY

Condensation of thiazolinone 1 with benzaldehydes 2a, b in ethanolic piperidine afforded the methylidene derivatives 3a, b. Cyclocondensation of compound 3b with malononitrile furnished the novel thiazolo[3,2-a]-pyridine 5. Also, compound 3b was condensed with dimethylformamide-dimethylacetal (DMF-DMA) and triethylortho-formate to yield N,N-dimethylamino 6 and ethoxymethylene 7 derivatives respectively. The novel thiazolo[3,2-a]pyridines 10a, b were obtained by cyclocondensation of compounds 3a, b with benzylidene-malononitriles 8a, b. Similarly, cyclocondensation of compound 3b with benzylidenemalononitrile 11 afforded the thiazolopyridines 12a–c. Ternary condensation of compound (12), 4-morpholinobenzaldehyde 2b and malononitrile (1:1:1 molar ratio) produced the thiazolopyridines 14a–c. When compound 10b was subjected to react with malononitrile in dioxane/piperidine under reflux the novel condensed heterocyclic system 18 was obtained. Treatment of ortho-aminocarbonitrile 10b with formic acid, aromatic aldehyde and triethylorthoformate furnished the thiazolo[2′,3′:1,6] pyrido[2,3-d] pyrimidine 20, azomethine 21a, b and ethoxymethylene 22 derivatives respectively. The structure of the synthesized compounds was established by analytical and spectral data.