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.     

Synthesis and anti-inflammatory activities of some thiazolo[3,2-a]pyrimidine derivatives.

Sixteen new 2-benzylidene-7-methyl-3-oxo-5-(substituted phenyl)-2, 3-dihydro-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid methyl esters (1a-4d) have been synthesized by reacting 1,2,3,4-tetrahydropyrimidine-2-thiones (1-4) with chloroacetic acid and appropriate benzaldehydes in a single step. Their structures have been proved by IR, 1H NMR, mass spectra and elemental analysis. The compounds were tested for their anti-inflammatory activities. Test results revealed that compounds 1b, 1c, 4a and 4c exerted moderate anti-inflammatory activity at the 100 mg/kg dose level compared with indomethacin.     

Synthesis and antitumor activity of certain new thiazolo[2,3-b]quinazoline and thiazolo[3,2-a]pyrimidine analogs

A novel series of thiazolo[2,3-b]quinazoline (16–19, 25–28, and 34–37) and cyclohepta[d]thiazolo[3,2-a]pyrimidine (20–23, 29–32, and 38–41) analogs was designed and synthesized. Structure elucidation of the synthesized compounds was attained by the use of H¹ NMR, C¹³ NMR, and mass spectrometry. The obtained compounds were evaluated for their in vitro antitumor activity using the National Cancer Institute’s 60 cell lines’ panel assay that included nine tumor subpanels, namely, leukemia, non-small cell lung, colon, CNS, melanoma, ovarian, renal, prostate, and breast cancer cells. Most of the investigated compounds showed a remarkable broad-spectrum antitumor activity. Compounds 19, 28, 32, and 34 proved to be 10-, 15-, 2-, and 7-fold more active than 5-FU, with GI₅₀ MG-MID values of 2.4, 1.5, 11.2, and 3.1 μM, respectively.     

Synthesis and antioxidant properties of 3-methyl-substituted thiazolo[3,2-a]benzimidazole

3-Aminomethyl-substituted thiazolo[3,2-a]benzimidazoles were synthesized by reacting 3-(chloromethyl) thiazolo[3,2-a]benzimidazole with primary and secondary amines. The resulting 3-amino-derivatives of thiazolobenzimidazole were tested in vitro for antioxidant properties in relation to the autooxidation of adrenaline to adrenochrome. All the compounds studied inhibited, to different extents, the oxidation of adrenaline to adrenochrome, thus preventing formation of the superoxide radical. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 41, No. 6, pp. 20–21, June, 2007.     

Antihypertensive Effect of some Oxazolo[3,2-a]pyridines,Thiazolo[3,2-a]pyridines and Pyrido[2,1-b]oxazines in Conscious Spontaneously Hypertensive Rats

The antihypertensive activity of eighteen oxazolo[3,2-a]pyridine, fhiazolo[3,2-a]pyridine and pyrido[2,1-b]oxazine derivatives has been evaluated in conscious spontaneously hypertensive rats (SHRs), and compared with that of nifedipine, used as reference. At a dose of 50 mg kg^?1 (i.p.) eleven compounds resulted in a significant reduction in mean arterial blood pressure; four of the eleven were particularly effective, resulting in significant hypotension more than 6 h after administration and an effect that was still apparent after 24 h. The hypotension induced by nifedipine gradually decreased, disappearing 6–8 h after administration. The long-lasting activity shown by these compounds is, in general, not accompanied by reflex tachycardia. Intraperitoneal administration of two oxazolo[3,2-a]pyridine derivatives and two pyrido[2,1-b]oxazine derivatives resulted in potent and long-lasting antihypertensive action in SHRs. Further studies on the mechanism of action of these derivatives might help the determination of better structure–activity correlations and the design, synthesis and evaluation of better antihypertensive agents.     

Synthesis, reactions and antimicrobial activity of new cyclopenta[e]thieno[2,3-b]pyridines and related heterocyclic systems

Reaction of the arylidene cyanothioacetamides 1a, b with cyclopentanone was proved to give a mixture of 4-aryl-3-cyanocyclopenta[b]pyridine-2(1H)-thiones 2a, b and the corresponding 7-arylidene derivatives 3a, b. Compounds 2a, b were reacted with ethyl chloroacetate or chloroacetamide to give the promising S-substituted thiopyridines 6a-d. On treatment of the latter compounds with sodium ethoxide in boiling ethanol, they underwent intramolecular Thorpe-Ziegler cyclization to yield the corresponding 3-amino-4-aryl-2-functionalized-cyclopenta[e]thieno[2,3-b]pyridines (7a-d). Most of these thienopyridines were reacted with a variety of reagents to produce other new cyclopentathienopyridines as well as numerous of their condensed heterocyclic derivatives. Some of the compounds synthesized were tested in vitro for their antibacterial and antifungal activity.     

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.     

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.     

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.     

New 5H-[1,3]thiazolo[3,2-a]pyrido[3,2-e]pyrimidine derivatives as diuretics

New 5H-[1,3]thiazolo[3,2-a]pyrido[3,2-e]pyrimidines 1 and 6,10-dihydro-5H-pyrido[3',2':5,6]pyrimido[2,1-c] [1,2,4]triazines 4 with 5-one, 5-thione or 5-hydrazono substituents and in some cases 1,2,3,4 or 8,9 hydrogenated are synthetized. The diuretic, natriuretic and kaliuretic activities of these compounds in Wistar rats at a dose of 24 mg/kg were estimated. A series of 24 possible derivatives of 1 and 4 possessing diuretic and saliuretic activities are investigated for structure-activity relationships in light of Fujita-Ban model. The Fujita-Ban group contributions have been calculated for different structural variations on the parent ring 1a. It is observed that the hydrogenation of pyridine, [1,3]thiazole or [1,2,4]triazine rings on 1 or 4 decrease the diuretic and saliuretic activities.     

Synthesis and pharmacological evaluation of newer thiazolo [3,2-a] pyrimidines for anti-inflammatory and antinociceptive activity

A new series of thiazolo [3,2-a] pyrimidine derivatives was designed and synthesized using 4-fluoroaniline and ethylacetoacetate as starting material. Anti-inflammatory activity was assessed by the rat paw edema method and antinociceptive activity was evaluated by thermal stimulus technique. The compounds 5-(4-chlorophenyl)-2-(4-fluorobenzylidene)-7-methyl-3-oxo-2,3-dihydro-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid (4-fluorophenyl)amide (3l) and 2-(4-chlorobenzylidene)-5-(4-fluorophenyl)-7-methyl-3-oxo-2,3-dihydro-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid (4-fluorophenyl)amide (3q) were found to possess significant anti-inflammatory and antinociceptive activities. These compounds also showed lower ulcerogenic activity and higher ALD₅₀ values. Compounds with an aryl ring substituted with a smaller electron withdrawing group at the fourth position displayed better activity than the other derivatives.     

Synthesis of imidazo[4,5-d]oxazolo[3,4-a]pyridines. New heterocyclic analogues of lignans.

The preparation of new analogues of lignans carrying an imidazole ring has been achieved. Starting from L-histidinol, cis and trans stereoisomers have been obtained. The synthesized products lack the cytotoxicity displayed by related podophyllotoxins and azatoxin.     

Synthesis and hypoglycemic activity of some substituted 2-arylthiazolo[3,2-a]pyridinium salts

A series of substituted 2-arylthiazolo[3,2-a]pyridinium salts (1a-q) was prepared by known methods and tested for hypoglycemic activity in 48-h fasted rats. Two compounds, 2-phenylthiazolo- and 8-methyl-2-phenythiazolo[3,2-a]pyridinium perchlorate (1a and 1q), showed consistent hypoglycemic activity in this screen, demonstrating that a high degree of structural specificity was required for hypoglycemic activity. At higher doses the hypoglycemic activity of 1a and 1q was associated with elevated levels of hepatic triglycerides.     

Synthese und Bioaktivität einiger 4-Oxo-naphtho[1,2-d]thiazolo[3,2-a]pyrimidin-Derivate

Synthesis and Bioactivities of Some Derivatives of Naphtho[1,2-d]thiazolo[3,2-a]pyrimidin-4-one In continuing the study of the structure-activity relationships of compounds of the naphtho[1,2-d]thiazolo[3,2-a]pyrimidine series, the 4-oxo derivatives 5a–d were synthesized in addition to the 2-oxo compounds reported previously. The synthesis was accomplished by nucleophilic attack of 2-aminonaphtho[1,2-d]thiazole (2) on the corresponding β-keto esters 3a–d . Unlike the 2-oxo derivatives, the products showed no hypotensive effect on normotensive rats. However, all compounds exhibited a pronounced diuretic activity in the same animals after oral administration of 10–30 mg/kg. The activity persisted in most cases for more than five hours.     

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 immunotropic activity of derivatives of thiazolo[3,4-a]benzimidazole

Translated from Khimiko-farmatsevticheskii Zhurnal, Vol. 25, No. 1, pp. 40–42, January, 1991.     

Synthesis and antimicrobial evaluation of some new thiazolo[4,5-d] pyrimidines.

In this study, by starting from ethyl 4-amino-2,3-dihydro-3-methyl-2-thioxothiazole-5-carboxylate (1), the compounds having 2,3-dihydro-3-methyl-5-mercapto-6-methyl/ethyl-2- thioxothiazolo[4,5-d]pyrimidin-7(6H)-one (2a, 2b) structure and their 5-(4'-nonsubstituted/-substituted benzoylmethyl)thio derivatives (3a-h) were synthesized. The chemical structures of the compounds were proved by IR, 1H-NMR and elemental analysis data. In vitro antimicrobial activities of the synthesized compounds were investigated against some bacteria and yeasts using the microdilution method. In view of the antimicrobial activity results, a significant inhibitory effect was observed only for compound 2a against Gram-positive bacteria and yeasts, whereas the other compounds had no remarkable activity against the tested microorganisms.