Reactions with hydrazidoyl halides VIII: Synthesis of thiazolo [3,2-a] benzimidazoles,imidazo[2,1-b] thiazoles and imidazo[2,1-b] benzthiazoles

Hydrazidoyl halides were condensed with 2-mercaptobenzimidazole2 yielding4a-c which were cyclized to the corresponding 3-substituted 2-arylazothiazolo-[3,2-a] benzimidazole6a-c, respectively. Imidazo-[2,1-b] thiazoles9, 12, 15, and16 were obtained by the reaction of hydrazidoyl halides1 with 2-mercapto 4,5-dihydroimidazole3 and 2-aminothiazoles10. The structures of the products were established on the basis of their elemental analysis and spectral data studies.     

Synthesis and biological evaluation of some pyrimidine, pyrimido[2,1-b][1,3]thiazine and thiazolo[3,2-a]pyrimidine derivatives

4,6-Diamino-1H-pyrimidine-2-thione (1) was used for the preparation of pyrimidine derivatives 2-5. Compound 5 was cyclized to produce pyrimido[2,1-b][1,3]thiazine derivative 6 which was condensed with p-chlorobenzaldehyde to give compound 7. The latter compound was reacted with hydroxylamine to give isoxazolo[4,5-d]thiazino[2,3-a]pyrimidine 8. Compound 8b was treated with 2-chloroethyl methyl ether to afford compound 9. Similarly, compound 3 reacted with chloroacetic acid to give thiazolo[3,2-a]pyrimidine 10, which was condensed with p-chlorobenzaldehyde to give compound 11. Compound 11 was condensed with hydroxylamine to give isoxazolo[4,5-d]thiazolo[2,3-a]pyrimidine 12. Compound 12b was treated with 2-chloroethyl methyl ether to afford compound 13. Biological evaluation of some prepared products showed that many of them revealed promising antimicrobial activity.     

Imidazo[2,1-b]-1,3,4-thiadiazolo[3,2-a]pyrimidone-(6) aus 2-Acetoacetylamino-imidazo[2,1-b]-1,3,4-thiadiazolen

Imidazo[2,1-b]-1,3,4-thiadiazolo[3,2-α]pyrimidin-6-ones by Cyclisation of 2-(Acetoacetylamino)-imidazo[2,1-b]-1,3,4-thiadiazoles The 2-acetoacetylamino-6-methyl- (or -aryl) imidazo[2,1-b]-1,3,4-thiadiazoles 1, 2a–f cyclise on heating in polyphosphoric acid (PPA) to yield the tricyclic 2,8-dimethyl- or 2-aryl-8-methyl-imidazo[2,1-b]-1,3,4-thiadiazolo[3,2-α]pyrimidin-6-ones 3, 4a–f . Only 4c inhibits the growth of vaccinia viruses. The other compounds have no antiviral activity.     

Synthesis of some new thiazolo[3,2-a]pyridines and related heterocyclic systems

New 2,7-disubstituted 5-amino-6,8-dicyano-2,3-dihydro-3-oxo thiazolo[3,2-a]pyridines have been prepared. Their cyclization with formamide, nitrous acid and triethylorthoformate afforded a series of polycyclic heterocycles containing condensed pyrimidine and triazine rings. Antifungal tests were also performed.     

Synthesis and Structural Evaluations of Thiazolo[3,2-a]pyrimidine Derivatives

2-Thioxo-1,2,3,4-tetrahydropyrimidine derivatives 1 were reacted with phenacyl bromide in glacial acetic acid to obtain thiazolo[3,2-a]pyrimidine derivatives. UV-, IR-, and ¹H-NMR spectra and elementary analysis data confirm structures 3. ¹H-{¹H}-NOE techniques showed that the isolated products are H-5 isomers.     

Antitrichomonal activity of mesoionic thiazolo[3,2-a]pyridines

Screening of mesoionic compounds as potential electron acceptors by analogy with metronidazole led to the finding of in vitro antitrichomonal activity for anhydro-2-phenyl-3-hydroxythiazolo [3,2-a]pyridinium hydroxide (1). In a series of analogues, potent in vitro activity was found to be associated with amino substitution; however, such activity was dependent on specific structural features and not on the reduction potential. The most active compounds showed only poor in vivo activity.     

Bisbenzofuro[3,2-b: 2',3'-e]pyridines

Heating the potassium 3-enaminobenzo[b]furan-2-carboxylate 3 in acetic acid on 110 degrees C yielded the pentacyclic acetate 6. The acetic acid 7, formed by hydrolysis of the ester 6, decarboxylated easily giving 6-methyl-bis[1]benzofuro[3,2-b: 2',3'-e]pyridine (8).     

Synthesis and biological activity of pyrimido[2,1-b][1,3]thiazine, [1,3]thiazino[3,2-a]purine and [1,2,3]triazolo[4,5-d][1,3]thiazino[3,2-a]pyrimidine derivatives and thiazole analogues.

Some series of thiazolo[3,2-a]pyrimidine, pyrimido[2,1-b] [1,3]thiazine, thiazolo[3,2-a]purine, [1,3]thiazino[3,2-a]purine, thiazolo[3,2-a][1,2,3]triazolo[4,5-d]pyrimidine and [1,2,3]triazolo[4,5-d][1,3]thiazino[3,2-a]pyrimidine derivatives, variously functionalized, were prepared. The compounds were tested for antimicrobial and antimycotic activity on a number of strains, namely: E. coli, Proteus vulgaris, P. mirabilis, Pseudomonas aeruginosa, Salmonella sp., Staphylococcus aureus, S. faecalis, Bacillus subtilis, Sarcina lutea, Candida albicans, C. tropicalis, Aspergillus sp., and for antiviral activity on Herpes simplex virus Type 1, Vesicular stomatitis virus and Coxsackievirus B5. The compounds proved to be devoid of activity against viruses and gram-negative bacteria, while some of them exhibited modest activity against gram-positive bacterial strains.     

Synthesis of potential anticancer agents. Pyrido[4,3-b][1,4]oxazines and pyrido[4,3-b][1,4]thiazines

Hydrolysis of the chloro group of ethyl (6-amino-4-chloro-5-nitropyridin-2-yl)carbamate (3) with formic acid gave the corresponding 4-hydroxypyridine 4. Catalytic hydrogenation of the nitro group of 4 gave the 5-amino-4-hydroxypyridine 5, which was reacted with alpha-halo ketones in acetic acid at room temperature to give a series of 3- and 2,3-substituted ethyl (5-amino-2H-pyrido[4,3-b][1,4]oxazin-7-yl)carbamates 8. Treatment of 8 with hot concentrated hydrochloric acid regenerated the pyridine synthon 5. In the reaction of 3 with thioacetate, the product underwent hydrolysis and air-oxidation to give the corresponding disulfide 6. Simultaneous reduction of both the nitro group and disulfide linkage of 6 gave the 5-amino-4-mercaptopyridine 7, which was reacted with alpha-halo ketones either in acetic acid at room temperature or in a mixture of ethanol and water at reflux to give a series of 3-, 2,3-, and 2,2,3-substituted ethyl (5-amino-2H-pyridol[4,3-b][1,4]thiazin-7-yl)carbamates 9. The effects of these pyridooxazines and pyridothiazines upon the proliferation and the mitotic index of cultured L1210 cells and upon the survival of mice bearing P388 leukemia were determined.     

Pyrido [3,2-b]indol-4-yl-amines--synthesis and investigation of activity against malaria

Pyrido[3,2-b]indol-4-yl-amines--synthesis and investigation of activity against malaria Starting with 3-aminoindole-2-carboxylic acid ester 1 the annulated pyrido[3,2-b]indoles 6 and 8 were synthesized as key substances. The 4-chloropyridine derivative 8 reacted with the phenol Mannich bases 11 and the novaldiamine base 13, respectively, to yield the amodiaquine and cycloquine analogues 12 as well as the chloroquine analogue 14. The stability of the compounds 12 and 14 were proven by the half wave potentials measured by differential pulse voltammetry. Compounds 12 and 14 were tested for in vitro antimalarial activity using a chloroquine sensitive and a chloroquine resistant Plasmodium falciparum strain. The highest activity was shown by 12g with IC50 values of 50 nM and 38 nM, respectively. The in vivo activity of 12g was tested in Plasmodium vinckei infected mice resulting in ED50 values of 22 mg/kg and 26 mg/kg after intraperitoneal and oral administration, respectively.     

Synthesis of Some New Derivatives of Thiazolo[4,3-b]- and Thiazolo[2,3-b] quinazolone

The new 5H-thiazolo[4,3-b]quinazoline-3,5(1H)-diones 3, 4a–c, 5a–c and 5H-thiazolo[2,3-b]quinazoline-3,5(2H)-diones 9a–c, 11a–c were prepared by reaction of anthranilic acid with the 2-thiazolidinone-4-thione derivatives 1b, 6a–c, 7a–c and the 5-substituted 2-(alkylmercapto)-2-thiazolin-4-ones 8a-c, 10a-c , respectively.     

Synthesis of 1,3,4-thiadiazoles, imidazo[2,1-b]1,3,4-thiadiazoles and thiadiazolo[3,2-a]pyrimidines derived from benzimidazole as potential antimicrobial agents

Several new 1,3,4-thiadiazole, imidazo[2,1-b]1,3,4-thiadiazole and thiadiazole[3,2-al]pyrimidine derivatives of benzimidazole were synthesized. The compounds were obtained from 1-ethyl or benzyl 2-(2-amino-1,3,4-thiadiazol-5-yl)thiomethylbenzimidazole. The antimicrobial activity of the prepared compounds was studied.     

Enaminones in heterocyclic synthesis part 2: One-pot synthesis of some new indeno [3,2-b] pyridines

Six new indeno[3,2-b]pyridine derivatives were synthesized via reactions of 1-phenyla-mino-3-indenone with cyano olefins.     

Condensed Heterocyclic Compounds: Synthesis and Antiinflammatory Activity of Novel Thiazolo[3,2-a]pyrimidines

In this study, thirty six new 2-benzylidene-7-methyl-3-oxo-5-phenyl-2,3-dihydro-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid methyl esters were synthesized and characterized by spectral, crystallographic, and elemental analysis. The antiinflammatory activity of the compounds was tested by the carrageenan hind paw edema test. It was found that compound 6a having a 2-methoxyphenyl group at position 5 and a benzylidene group at position 2 was the most potent compound in this series. All the compounds that were tested for ulcer activity gave positive results.     

Synthesis and oral antiallergic activity of carboxylic acids derived from imidazo[2,1-c][1,4]benzoxazines, imidazo[1,2-a]quinolines, imidazo[1,2-a]quinoxalines, imidazo[1,2-a]quinoxalinones, pyrrolo[1,2-a]quinoxalinones, pyrrolo[2,3-a]quinoxalinones, and imidazo[2,1-b]benzothiazoles

4H-Imidazo[2,1-c][1,4]benzoxazine-2-carboxylic acid (3) was found to possess potent activity in the IgE-induced rat passive cutaneous anaphylaxis model which may be predictive of clinical antiallergic activity. Compared to disodium cromoglycate (DSCG, 1), 3 was less active following iv administration but unlike DSCG showed very significant oral activity. To explore the structural requirements for this activity, a range of tricyclic compounds was prepared and their activities were measured. Individual 2-carboxylic acids derived from imidazo[1,2-a]quinolines, imidazo[1,2-a]quinoxalines, imidazo[1,2-a]quinoxalinones, pyrrolo[1,2-a]quinoxalinones, pyrrolo[2,3-a]quinoxalinones, and imidazo[2,1-b]benzothiazoles showed iv activities up to 10(3) times as potent as DSCG and many of them showed significant oral activity. From these, imidazo[1,2-a]quinoxaline-2-carboxylic acid 114 has been chosen for further development.     

Synthesis and Biological Investigations of Some New Thiazolylbenzimidazoles and Benzimidazolylthiazolo[3,2-a]pyridines

2-[(4-Oxo-4,5-dihydrothiazol-2-yl)methyl]-1H-benzimidazole ( 2 ) was prepared through the reaction of 2-cyanomethyl-1H-benzimidazole ( 1 ) with thioglycolic acid. The syntheses of its arylidene 3 and diazo-coupled compounds 5 and the cyclization of the aforementioned thiazolylbenzimidazole to benzimidazolylthiazolo[3,2-a]pyridines 8 were also performed. The prepared compounds were screened for their in-vitro antibacterial, antifungal, anti-HIV, and anticancer activities: they show promising antifungal activity.     

Synthesis and anti-inflammatory evaluation of some pyrazolo[3,4-b]pyridines

Novel series of pyrazolo[3,4-b]pyridines with basic skeleton different from the known COX inhibitors were synthesized from 5-amino-1-[4-(aminosulfonyl)phenyl]-3-phenyl-1H-pyrazole, which in turn was prepared by the condensation of (4-sulfamoylphenyl)hydrazine with α-cyanoacetophenone. All the newly synthesized compounds were tested for their in vivo anti-inflammatory activity by carrageenan-induced rat paw edema assay. Some of the most potent compounds were evaluated in different COX and LOX assays. Some of the new compounds were found to possess moderate anti-inflammatory activity.