Synthesis and evaluation of some new 1,3,4-oxadiazoles bearing thiophene, thiazole, coumarin, pyridine and pyridazine derivatives as antiviral agents

In an attempt to produce heterocyclic compounds based on 1,3,4-oxadiazole derivatives with potential antiviral activity, the synthesis of compound 1 [2-(5-thioxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)acetonitrile] was performed through the reaction of cyanoacetic acid hydrazide with carbon disulfide in alcoholic potassium hydroxide. Compound 1 has an activating methylene group, so it was directed toward some specific reactions. Thus, aryldiazonium chlorides reacted with compound 1 affording hydrazono derivatives 2a,b,c. Also, aromatic aldehydes reacted with compound 1 to produce compounds 3a,b. Furthermore, cyclic ketones were subjected to synthesis of fused thiophene derivatives 4a,b via the reaction with compound 1 in the presence of elemental sulfur. In addition, 1,3,4-oxadiazole derivative 1 when reacted with isothiocyanates, salicylaldehyde or 1,3-dicarbonyl compounds formed thiazole derivatives 5a,b, coumarin derivative 6 and alkenyl derivatives 7a,b resp. Compound 7b underwent cyclization to afford pyridine derivative 8. Arylhydrazono derivatives 9a,b were produced through the reaction of compound 7a with aryldiazonium chlorides. The latter products 9a,b underwent cyclization to produce pyridazine derivatives 10a,b. Finally 1,3,4-oxadiazole derivative 1 was directed toward the reaction with hydrazine derivatives, bromoacetophenone and ethylchloroacetate affording compounds 11a,b, 12 and 13, resp. The fused thiophene derivatives 14a,b were produced via the reaction of compounds 4a,b with a mixture of malononitrile and ethylorthoformate. Antiviral activity of the synthesized products showed that 5-(4-amino-3-ethyl-2-thioxo-2,3-dihydrothiazol-5-yl)-1,3,4-oxadiazole-2(3H)-thione (5a) and 5-(4-amino-3-phenyl-2-thioxo-2,3-dihydrothiazol-5-yl)-1,3,4-oxadiazole-2(3H)-thione (5b) act as the most active agents against Feline herpes virus, Feline corona virus, Herpes simplex virus-1 and Herpes simplex virus-2, whereas compound 2-(5-(2-phenyl- hydrazono)-4,5-dihydro-1,3,4-oxadiazol-2-yl)acetonitrile (11b) was the most effective against Vaccinia virus, Herpes simplex virus (TK-KOS-ACVr ), Coxsackie virus B4 and Vesicular stomatitis virus

Synthesis of some novel pyrimidine, thiophene, coumarin, pyridine and pyrrole derivatives and their biological evaluation as analgesic, antipyretic and anti-inflammatory agents

Pyrimidine derivative 3 was afforded through the reaction of compound (1) with 5-ureidohydantion (2). Product 3 underwent a cyclization to produce fused pyrimidine derivative 7, although the latter product 7 was synthesized through one step via the reaction of compound (1) with 5-ureidohydantion (2) using another catalyst. Compound 3 was oriented to react with cyclic ketones 8a,b in the presence of elemental sulfur, salicylaldehyde (10), aryldiazonium chlorides 12a,b and ω-bromo-4-methoxy- acetophenone (14), which afforded, fused thiophene derivatives 9a,b, coumarin derivative 11, arylhdrazono derivatives 13a,b and 4-methoxyphenyl butenyl derivative 15, respectively. The latter product 15 was reacted with either potassium cyanide (16a) or potassium thiocyanide (16b) to form cyano and thiocyano derivatives 17a,b, respectively. Compound 17a underwent further cyclization to afford pyridopyrimidine derivative 19. Compound 15 was reacted with either hydrazine (20a) or phenylhydrazine (20b) to produce hydrazo derivatives 21a,b and these products were cyclize to produce pyrrole derivatives 23a,b. Finally, 5-ureidohydantion (2) was reacted with compounds 24a,b,c to afford pyrimidine derivatives 25a,b,c. The structures of the synthesized compounds were confirmed using IR, 1 H NMR, 13C NMR and mass spectrometry techniques. Compounds 11 and 19 have promising as analgesic and antipyretic activities

Reakcija β-amino-α,γ-dicianokrotononitrila s acetofenonom: sinteza derivata piridina, piridazina i tiofena s antimikrobnim djelovanjem

Condensation of β-amino-α,γ-dicyanocrotononitrile (1) with acetophenone gave the 2-amino-4-phenylpenta-1,3-diene-1,1,3-tricarbonitrile (2). The latter product was used in a series of heterocyclization reactions when react with different reagents like diazonium salts, hydrazines, hydroxylamine and elemental sulfur to give pyridazine, pyrazole, isoxazole and thiophene derivatives, respectively. On the other hand, it gave pyridine derivatives with aromatic aldehydes followed by reaction with cyanomethylene reagents. The MIC values for the newly synthesized product were measured against E. coli, B. cereus, B. subtilis and C. albicansKondenzacijom β-amino-α,γ-dicijanokrotononitrila 1 s acetofenonom dobiven je 2-amino-4-fenilpenta-1,3-dien-1,1,3-trikarbonitril (2) koji je upotrebljen u reakcijama heterociklizacije s različitim reagensima poput diazonijevih soli, hidrazina, hidroksilamina i elementarnog sumpora pri čemu su nastali derivati piridazina, pirazola, izoksazola, odnosno tiofena. Spoj 2 je u reakciji s aromatskim aldehidima te naknadno sa cijanometilenima dao derivate piridina. Određene su MIC vrijednosti za novosintetizirane spojeve protiv E. coli, B. cereus, B. subtilis i C. albicans

The Reaction of Cyanoacetic Acid Hydrazide with 2-Acetylfuran: Synthesis of Coumarin, Pyridine, Thiophene and Thiazole Derivatives with Potential Antimicrobial Activities

The hydrazide-hydrazone derivative 1 was formed through the reaction of cyanoacetic acid hydrazide with 2-acetylfuran. Compound 1 underwent a series of hetrocyclization reactions through its reaction with different chemical reagents to produce arylidene, coumarin, aryl hydrazone, pyridine, thiophene and thiazole derivatives 2–10. The MIC values for the newly synthesized products were tested against E. coli, B. cereus, B. subtilis and C. albicans compared with ampicilline and cycloheximide as reference drugs

Synthesis and antitumor activity of some novel thiophene, pyrimidine, coumarin, pyrazole and pyridine derivatives

2-Cyano-N-(thiazol-2-yl) acetamide (2a) and 2-cyano-N-(oxazol- 2-yl) acetamide (2b) were obtained via the reaction of ethyl cyanoacetate with either 2-aminothiazole (1a) or 2-aminooxazole (1b). The formed products were directed toward the reaction with cyclopentanone and elemental sulfur in the presence of triethylamine to give cyclopenta[b]thiophene derivatives (3a,b). The latter products were reacted with either ethyl cyanoacetate or malononitrile to form compounds 4a,b and 5a,b, respectively. Compounds 4a,b were aimed at synthesizing some heterocyclic compounds; thus internal cyclization reactions were introduced to form compounds 6a,b. Also, compounds 4a,b reacted with salicylaldehyde, hydrazine derivatives and either urea or thiourea to produce coumarin derivatives (7a,b), pyrazole derivatives (8a-d) and pyrimidine derivatives (9a-d), respectively. Reaction of either benzaldehyde or benzene diazonium chloride (11) with compounds 4a,b afforded compounds 10a,b and 12a,b, respectively. On the other hand, compounds 5a,b underwent internal cyclization to form pyrimidine derivatives 13a,b. Also, when compounds 5a,b reacted with either ethyl cyanoacetate or malononitrile, they gave pyridine derivatives (15a-d) through the formation of intermediates (14a-d). Finally, formation of fused pyrimidine derivatives (17a,b) was achieved through the reaction of compounds 5a,b and salicylaldehyde applying two different pathways. The first pathway used a catalytic amount of piperidine to form compounds 16a,b; the latter products underwent cyclization to give compounds 17a,b. The second pathway, using a catalytic amount of sodium ethoxide solution directly in one step, afforded compounds 17a,b. Structures of the newly synthesized compounds were established using IR, 1H NMR, 13C NMR and mass spectrometry and their antitumor activity was investigated. Some of these compounds showed promising inhibitory effects on three different cell lines. However, fused pyrimidine acetonitrile derivatives 6a and 6b exerted the highest inhibitory effect, comparable to that of doxorubicin

Synthesis and evaluation of some new 1,3,4-oxadiazoles bearing thiophene, thiazole, coumarin, pyridine and pyridazine derivatives as antiviral agents

In an attempt to produce heterocyclic compounds based on 1,3,4-oxadiazole derivatives with potential antiviral activity, synthesis of compound 1 [2-(5-thioxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)acetonitrile] was performed through the reaction of cyanoacetic acid hydrazide with carbon disulfide in alcoholic potassium hydroxide. Compound 1 has an activating methylene group, so it was directed toward some specific reactions. Thus, aryldiazonium chlorides reacted with compound 1 affording hydrazono derivatives 2a-c. Also, aromatic aldehydes reacted with compound 1 to produce compounds 3a,b. Furthermore, cyclic ketones were subjected to the synthesis of fused thiophene derivatives 4a,bvia reaction with compound 1 in the presence of elemental sulfur. In addition, 1,3,4-oxadiazole derivative 1, when reacted with isothiocyanates, salicylaldehyde or 1,3-dicarbonyl compounds, formed thiazole derivatives 5a,b, coumarin derivative 6 and alkenyl derivatives 7a,b resp. Compound 7b underwent cyclization to afford pyridine derivative 8. Arylhydrazono derivatives 9a,b were produced through the reaction of compound 7a with aryldiazonium chlorides. Products 9a,b underwent cyclization to produce pyridazine derivatives 10a,b. Finally, 1,3,4-oxadiazole derivative 1 was directed toward reaction with hydrazine derivatives, bromoacetophenone and ethylchloroacetate affording compounds 11a,b, 12 and 13, resp. Fused thiophene derivatives 14a,b were produced via reaction of compounds 4a,b with a mixture of malononitrile and ethylorthoformate. Antiviral activity of the synthesized products showed that 5-(4-amino-3-ethyl-2-thioxo-2,3-dihydrothiazol-5-yl)-1,3,4-oxadiazole-2(3H)-thione (5a) and 5-(4-amino-3-phenyl-2-thioxo-2,3-dihydrothiazol-5-yl)-1,3,4-oxadiazole-2(3H)-thione (5b) acted as the most active agents against Feline herpes virus, Feline corona virus, Herpes simplex virus-1 and Herpes simplex virus-2, whereas compound 2-(5-(2-phenylhydrazono)-4,5-dihydro-1,3,4-oxadiazol-2-yl)acetonitrile (11b) was the most effective against Vaccinia virus, Herpes simplex virus (TK-KOS-ACVr), Coxsackie virus B4 and Vesicular stomatitis virus

Synthesis of some novel pyrimidine, thiophene, coumarin, pyridine and pyrrole derivatives and their biological evaluation as analgesic, antipyretic and anti-inflammatory agents

Pyrimidine derivative 3 was afforded through the reaction of compound (1) with 5-ureidohydantion (2). Product 3 underwent a cyclization to produce fused pyrimidine derivative 7, although the latter product 7 was synthesized through one step via the reaction of compound (1) with 5-ureidohydantion (2) using another catalyst. Compound 3 was oriented to react with cyclic ketones 8a,b in the presence of elemental sulfur, salicylaldehyde (10), aryldiazonium chlorides 12a,b and ω-bromo-4-methoxy- acetophenone (14), which afforded, fused thiophene derivatives 9a,b, coumarin derivative 11, arylhdrazono derivatives 13a,b and 4-methoxyphenyl butenyl derivative 15, respectively. The latter product 15 was reacted with either potassium cyanide (16a) or potassium thiocyanide (16b) to form cyano and thiocyano derivatives 17a,b, respectively. Compound 17a underwent further cyclization to afford pyridopyrimidine derivative 19. Compound 15 was reacted with either hydrazine (20a) or phenylhydrazine (20b) to produce hydrazo derivatives 21a,b and these products were cyclize to produce pyrrole derivatives 23a,b. Finally, 5-ureidohydantion (2) was reacted with compounds 24a,b,c to afford pyrimidine derivatives 25a,b,c. The structures of the synthesized compounds were confirmed using IR, 1H NMR, 13C NMR and mass spectrometry techniques. Compounds 11 and 19 have promising as analgesic and antipyretic activities