Synthesis and antimicrobial study of fluoroquinolone-based 4-thiazolidinones

The title compounds 2-substituted phenyl-3-{1-cyclopropyl-6-fluoro-7-[4-(4-methoxyphenylpiperazin-1-yl]-4-oxo-1,4-dihydroquinoline} carboxamido-1,3-thiazolidin-4-ones 6a–j have been synthesized from lead molecule 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 1; this reacted with thionyl chloride to give acid chloride 2 and with hydrazine hydrate to afford hydrazide 3. The hydrazide 3 on condensation with substituted aromatic aldehydes a–j gave Schiff base; these on reaction with N-(4-methoxyphenyl) piperazine and thioglycolic acid furnished title compounds 6a–j. All of the synthesized compounds have been established by elemental analysis. IR and NMR spectral data and have been screened for antifungal and antibacterial activities.     

Synthesis of 6,7-dialkoxy-2-arylmethylidene-2,3- dihydrobenzo[4,5]imidazo[2,1-b][1,3]thiazol-3-ones exhibiting anti-inflammatory activity

New 6,7-dialkoxy-2-arylmethylidene-2,3- dihydrobenzo[4,5]imidazo[2,1-b][1,3]thiazol-3-ones (3a-h, 4b, c, e, g) were synthesized from 2-(5,6-dialkoxy-1H-benzo[d]imidazol-2-ylsulfanyl)acetic acids (1, 2) and corresponding aromatic aldehydes in acetic anhydride. The compounds 3e, f and 4b, g were also synthesized from corresponding aromatic aldehydes and 6,7-dialkoxy-2,3-dihydrobenzo[4,5]imidazo[2,1-b][1,3]thiazol -3-ones (5, 6) obtained by the cyclization of the acids 1 and 2 in acetic anhydride. The synthesized compounds 3a-h and 4b, c, e, g exhibit anti-inflammatory activity.     

Synthesis, anti-HIV and anticancer activities of new 4-(2-mercaptobenzenesulfonyl)perhydro-1,2,4-triazin-3-ones

Syntheses of N-(6-chloro-1,1-dioxo-7-R1-1,4,2-benzodithiazyn-3-yl)-N'-(2- hydroxyethyl)hydrazines (IIa-d], N-(6-chloro-1,1-dioxo-7-methyl-1,4,2-benzodithiazyn-3-yl)-N'-(2- chloroethyl)hydrazine [IV], 4-(4-chloro-5-R1-2-mercaptobenzenesulfonyl)perhydro-1,2,4-triaz in-3-ones [IIIa-d] and 5-chloro-4-methyl-2-(3-oxoperhydro-1,2,4-triazin-4- ylsulfonyl)phenylthioacetic acid [V] have been described. Preliminary screening data have indicated that compounds [IIIa-d] exhibit either a moderate or a high anti-HIV activity and a moderate anticancer activity in some human tumor cell lines.     

Synthesis and Antimicrobial Activities of Some New Azetidin-2-ones and Thiazolidin-4-ones

Various (4-substituted) phenyl-3-β-[(N-benzenesulphonyl/tosyl)-4-(un)substituted anilino]propionylamido-1,3-thiazolidine-4-ones (3a-x) and 1-β-[(N-benzenesulphonyl/tosyl)-4-(un)substituted anilino]-propionylamido-3-chloro-4-(4-substituted)phenyl-azetidin-2-ones (4a-x) have been synthesised by the cyclocondensation of Schiff bases (2a-x) with thioglycolic acid and chloroacetyl chloride, respectively. The structures of the newly synthesised compounds have been established on the basis of their spectral data and elemental analysis. All compounds were evaluated for antimicrobial activities against Escherichia coli, Bacillus cirroflagellosus, Aspergillus niger and Colletotrichum capsici. Most compounds investigated exhibited significant antifungal activity against Colletotrichum capsici, comparable to that of fluconazole, the standard used.     

Synthesis and evaluation of some novel quinazolinone derivatives as diuretic agents

A new series of quinazolin-4(3H)-one derivatives containing either a thiazole or a 1, 3, 4-thiadiazole moiety were prepared in order to study the effect of such a heterocyclic combination on the expected diuretic activity. Synthesis of the target compounds (2, 4, and 6) has been achieved through an interaction of the starting 7-chloro-2-methyl-4H-3, 1-benzoxazin-4-one 1 with different heterocyclic amines. Alkylation of 3-(2-mercapto-1, 3, 4-thiadiazol-5-yl)quinazolin-4(3H)-one derivative 4 with different alkyl halides or chloroacetic acid afforded the corresponding thioethers 5 while interaction of 2-methyl-3-(1, 3, 4-thiadiazol-5-yl or thiazol-5-yl)quinazolin-4(3H)-ones (2 and 6) with various aromatic aldehydes resulted in the formation of the arylvinyl analogs 3 and 7, respectively. On the other hand, 2-morpholinomethyl-3-(2-sulfamoyl or mercapto-1, 3, 4-thiadiazol-5-yl)quinazolin-4(3H)-one derivatives 10 have also been synthesized through an interaction of the sulfonamide or thiol analog 9 with the appropriate amine. Biological evaluation of some of the target compounds as diuretic agents was carried out. The results showed that 2-[2-(4-chlorophenyl)vinyl]-7-chloro-3-(2-sulfamoyl-1, 3, 4-thiadiazol-5-yl)quinazolin-4(3H)-one 7b exhibited significant diuretic activity. The detailed synthesis, spectroscopic and biological data are reported.     

A new series of benzodiazepines. 1-Hydroxyalkyl derivatives of 1,3-dihydro-2H-1,4-benzodiazepin-2-ones.

A series of new 1-hydroxyalkyl derivatives of 1,3-dihydro-2H-1,4-benzodiazepin-2-ones bearing a 3-hydroxyl or a 4-N-oxide function together with some related compounds have been synthesized. Compound (22) [1-(2-hydroxyethyl)-3-hydroxy-7-chloro-1,3-dihydro-5-(o-fluorophenyl)-2H-1,4-benzodiazepin-2-one] has been selected for further studies both in animals and in humans as an antianxiety-sedative agent.     

Synthesis and antituberculosis activity of cycloalkylidenehydrazide and 4-aza-1-thiaspiro[4.5]decan-3-one derivatives of imidazo[2,1-b]thiazole

New N2-cycloalkylidene-(6-phenyl/4-chlorophenylimidazo[2,1-b]thiazol-3-yl) acetic acid hydrazides (2a-h and 3a-b) were synthesized by reacting (6-phenyl/4-chlorophenylimidazo[2,1-b]thiazol-3-yl)acetic acid hydrazides with cyclohexanones or cyclopentanone. Furthermore, 2a-h were refluxed with thioglycolic or thiolactic acid to give 4-[[(6-phenyl/4-chlorophenylimidazo[2,1-b]thiazol-3-yl) acetyl]amino]-4-aza-1-thiaspiro[4.5]decan-3-ones (4a-h and 5a-h). The structures of the title compounds were established by spectral data (IR, 1H-NMR, 13C-NMR and EIMS (Electron Impact Mass Spectrometry)) and elemental analysis. The synthesized compounds were evaluated for antituberculosis activity against Mycobacterium tuberculosis H37Rv (ATCC 27294). The compounds exhibited varying degrees of inhibition in the in vitro primary screening that was conducted at a concentration of 6.25 micrograms/ml against M. tuberculosis H37Rv (ATCC 27294) in Bactec 12B medium using the Bactec 460 radiometric system or a broth microdilution assay, the Microplate Alamar Blue Assay (MABA). Compounds 2f, 2h, 3b, 4a, 4c, 4d, 5a-e and 5h demonstrating at 1-east 90% inhibition in the primary screen were re-tested at lower concentrations against M. tuberculosis H37Rv (ATCC 27294) to determine the actual minimum inhibitory concentration (MIC) using MABA. The most active compounds were found to be 4d and 5c. The structure-activity relationships of the derivatives were investigated.     

Synthesis of some novel quinoline-3-carboxylic acids and pyrimidoquinoline derivatives as potential antimicrobial agents

The synthesis and in vitro antimicrobial evaluation of several quinoline and pyrimidoquinoline derivatives are described. Treatment of 7-substituted quinolin-2(1H)-one-3-carboxylic acids 2a-c with phosphoryl chloride or thionyl chloride gave rise to the 7-substituted 2-chloroquinoline-3-carboxylic acids 3a-c and 7-substituted 2-chloro-3-chlorocarbonylquinolines 5a-c respectively. The 2-chloro function in compounds 3a-c was replaced by 2-aminothiazole or 2-aminopyridine to give 2-(thiazol-2-yl)aminoquinoline-3-carboxylic acids 4a-c or 2-(pyrid-2-yl)aminoquinoline-3-carboxylic acids 4d-f. Treatment of 5a-c with the same heterocyclic amines at room temperature furnished the corresponding 7-substituted 2-chloro-3-heteryl-aminocarbonylquinolines 6a-f. The tetracyclic 9-substituted thiazolo[3', 2':1, 2]-pyrimido[4, 5-b]quinolin-5-ones 7a-c and 10-substituted pyrido[1', 2':1, 2]-pyrimido[4, 5-b]quinolin-6-ones 7d-f were synthesized by heating 5a-c with the heterocyclic amines in toluene or by heating 6a-f under reflux in dimethylformamide. The products were evaluated in vitro for potential antimicrobial activity.     

Facile diversity-oriented synthesis and antitubercular evaluation of novel aryl and heteroaryl tethered pyridines and dihydro-6H-quinolin-5-ones derived via variants of the Bohlmann-Rahtz Reaction

The diversity oriented synthesis of substituted pyridines and dihydro-6H-quinolin-5-ones tethered with aryls and heteroaryls was achieved in very good yields through CeCl(3)·7H(2)O-NaI catalyst via variants of the Bohlmann-Rahtz reaction. β-Enaminones derived from various aryl and heteroaryl methyl ketones were regioselectively reacted with ethyl acetoacetate or 5,5-dimethylcyclohexane-1,3-dione or 4,4-dimethylcyclohexane-1,3-dione and ammonium acetate refluxing in 2-propanol. Applicability of nontoxic cerium catalyst, high reactivity with wide range of aryl and heteroaryl β-enaminones leading to diverse analogues, operational simplicity, and shorter reaction time at comparatively low temperatures are prominent features of the developed protocol. These synthesized substituted pyridines and dihydro-6H-quinolin-5-one analogues have been evaluated for their in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv (MTB) by agar dilution method. Among the 48 compounds screened, six compounds 2-(5-chlorothiophen-2-yl)-7,7-dimethyl-7,8-dihydro-6H-quinolin-5-one 4{13,2}, 2-(5-bromothiophen-2-yl)-7,7-dimethyl-7,8-dihydro-6H-quinolin-5-one 4{14,2}, 2-(5-chloro thiophen-2-yl)-6,6-dimethyl-7,8-dihydroquinolin-5(6H)-one 4{13,3}, and 2-(5-bromothiophen-2-yl)-6,6-dimethyl-7,8-dihydroquinolin-5(6H)-one 4{14,3}, 7,7-dimethyl-2-(naphthalen-2-yl)-7,8-dihydroquinoline-5(6H)-one 4{6,2}, 6,6-dimethyl-2-(naphthalen-2-yl)-7,8-di hydroquinolin-5(6H)-one 4{6,3} resulted as the most promising antitubercular agents.     

Search for new pharmacophore as antimalarial agent: synthesis and antimalarial activity of some 2(3H)-furanones bearing quinoline moiety

A series of substituted 3-[(substituted-2-chloroquinolin-3-yl)methylene]-5-(substituted-phenyl)-furan-2(3H)-ones (4a-p) have been synthesized and evaluated for their in vitro antimalarial activity against P. falciparum. The title compounds were synthesized by condensing 3-(substituted-benzoyl)propionic acids (3a-d) with substituted 2-chloroquinoline-3-carbaldehydes (2a-d) following modified Perkin's reaction. Compounds 3-[2-chloro-6-methylquinolin-3-yl)methylene]-5-(2,4-dimethyl-phenyl)-furan-2(3H)-one (4n) and 3-[2-chloro-6-methoxyquinolin-3-yl)methylene]-5-(2,4-dimethyl-phenyl)-furan-2(3H)-one (4p) showed promising antimalarial activity with MIC of 10 microg/mL.     

Synthesis, characterization, anticancer, and antioxidant activity of some new thiazolidin-4-ones in MCF-7 cells

There are limited studies centring on the potential of thiazolidin-4-ones as anticancer agents. In this study, a new series of 2-(3-substituted-1H-pyrazol-4-yl)-3-(3-substituted-5-sulfanyl-1,2,4-triazol-4-yl)-1,3-thiazolidin-4-one (4a–o) have been synthesized by cyclo-condensation reaction of 5-substituted-4-[(3-substituted-1H-pyrazol-4-ylmethylidene)amino]-2H-1,2,4-triazole-3-thione (3a–o) and thioglycolic acid. The structures of all the synthesized compounds were confirmed by elemental analysis, spectral techniques like IR, ¹H NMR, and mass spectroscopy. Few compounds exhibited dose-dependent cytotoxic effect in MTT assay in human breast cancer (MCF-7) cells. Apoptotic degradation of DNA due to action of potent thiazolidin-4-ones was analysed by agarose gel electrophoresis and visualized by ethidium bromide staining (comet assay). A concentration-dependent increase in tail length and olive tail moment was observed when treated with thiazolidin-4-ones. In vitro antioxidant studies like DPPH and ABTS-free radical scavenging assays-indicated moderate activity of thiazolidin-4-ones.     

Synthesis and antibacterial activity of thiosemicarbazones of 3-acylquinolones]

Oxidation of 3-acetyl derivatives of 3-acetyl-1-ethyl-1,4-dihydro-6,7-methylenedioxyquinoline-4-one (VIc) and 3-acetyl-7-chloro-1-ethyl-6-fluoro-1,4-dihydroquinoline-4-one (VId) with selenium dioxide provided the corresponding acids, [1-ethyl-1,4-dihydro-6,7-methylenedioxy-4-oxoquinoline-3-yl]glyoxylic acid (VIe) and [7-chloro-1-ethyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-yl]glyoxylic acid (VIf), respectively. Reactions of compounds VIc--VIf with thiosemicarbazide yielded the respective thiosemicarbazones of 3-acetyl-1-ethyl-1,4-dihydro-6,7-methylenedioxyquinoline-4-one (VIIa), 3-acetyl-7-chloro-1-ethyl-6-fluoro-1,4-dihydroquinoline-4-one (VIIb), [1-ethyl-1,4-dihydro-6,7-methylenedioxy-4-oxoquinoline-3-yl]glyoxylic acids (VIId). The compounds showed no significant in vitro antibacterial activity.     

Synthesis, Antiviral and Cytotoxic Activities of 2-(2-Phenyl carboxylic acid)-3-Phenylquinazolin -4(3H)-one Derivatives

A series of novel 2,3-disubstitutedquinazolin-4(3H)-ones have been synthesized by condensation of 2-substituted benzo[1,3]oxazine-4-ones and anthranilic acid. Synthesized compounds were evaluated for in vitro antiviral activity against HIV, HSV and vaccinia viruses. 5-Bromo-2-(6-bromo-4-oxo-2-phenyl-4H-quinazolin-3-yl)-benzoic acid (MBR2) exhibited distinct antiviral activity against Herpes simplex and vaccinia viruses.     

A study of anti-inflammatory activity of some novel alpha-amino naphthalene and beta-amino naphthalene derivatives

In the present study, some naphthalene derivatives have been synthesized by incorporating azetidinyl and thiazolidinyl moieties at its alpha- or beta-positions such as alpha-(3-chloro-2-oxo-4-substituted)aryl-1-azetidinyl)naphthalenes 6-10, alpha-((substituted)aryl-4-oxo-1,3-thiazolidin-3-yl)naphthalenes 11-15, beta-(3-chloro-2-oxo-4-substituted aryl-1-azetidinyl)naphthalenes 21-25, and beta-(substituted aryl-4-oxo-1,3-thiazolidin-3-yl)naphthalenes 26-30. These compounds have also been screened for acute toxicity and anti-inflammatory and analgesic activities. Compounds which showed better anti-inflammatory and analgesic activities were also examined for their ulcerogenic liability and underwent a cyclooxygenase assay. Two compounds, 12 and 28, were found to exhibit potent anti-inflammatory activity as compared to the standard drugs phenylbutazone and naproxen.     

Synthesis of some 1,2,4-triazolo[3,2-b]-1,3-thiazine-7-ones with potential analgesic and antiinflammatory activities

Starting from 3-substituted-1,2,4-triazole-5-thiones (la-h), eight new 5-carbomethoxy-2-substituted-7H-1,2,4-triazolo[3,2-b]-1,3-thiazine-7-ones (2a-h) were synthesized and characterized by spectral and elementary analysis. The obtained compounds were submitted to preliminary pharmacological assay to evaluate their antiinflammatory and analgesic activities as well as gastrointestinal irritation liability and acute toxicity. Among the compounds studied, compounds 2c, 2d, 2e and 2h showed most remarkable antiinflammatory activity in the carrageenan and serotonin induced edema and in the inhibition of castor oil-induced diarrhea tests. The analgesic activity of these active compounds correlated with their antiinflammatory activities in the inhibition of acetic acid-induced writhing test. In gastric ulceration studies, the compounds were found safety at low dose levels (10 and 20 mg/kg).     

Novel benzimidazole derivatives as expected anticancer agents

A series of 1-(1H-benzimidazol-2-yl)-3-(substituted)-2-propen-1-one and its 1-methyl analogues 2c-h were synthesized and cyclized with different reagents such as ethyl cyanoacetate, thiourea, hydroxylamine hydrochloride, guanidinium sulfate, methylhydrazine, phenylhydrazine and/or hydrogen peroxide in different reactions to produce pyridones 3a,b, pyrimidinethione 4a,b, isoxazole 5a,b, aminopyrimidine 6a,b, pyrazoline 7i-k and epoxy derivative 8, respectively. Acetohydrazide 10 reacted with formic acid, acetic anhydride, carbon disulfide and/or thiosemicarbazide to yield compounds 11-19. Also compound 21a,b was condensed with different monosaccharides to yield the corresponding N-glycoside Schiff's bases derivatives 22a-h, which upon treatment with acetic anhydride afforded 23a-h derivatives. The anticancer activity of some of the newly synthesized compounds was evaluated against HEPG2 (human liver carcinoma cell line) and PC12 (pheochromocytoma of the rat adrenal medulla) cells. Benzimidazole-2-isoxazole 5a derivative exhibited high potency against HEPG2 and PC12 cells. Benzimidazole chalcones 2c,e, benzimidazole mercaptoacetohydrazide 14 and benzimidazole thiosemicarbazide 15a,b derivatives gave high potency against PC12 cells.     

Synthesis and anti-inflammatory activity of certain piperazinylthienylpyridazine derivatives

In this study, a novel series of 2-(4-substituted piperazin-l-ylmethyl)-6-(thien-2-yl)-2H-pyridazin-3-ones (3a-f), 2-(4-substituted piperazin-l-yl carbonylmethyl)-6-(thien-2-yl)-2H-pyridazin-3-ones (4a-c) and 2-[2-(4-substituted piperazin-l-ylcarbonylethyl)]-6-(thien-2-yl)-2H-pyridazin-3-ones (5a,b) were prepared from 6-(thien-2-yl)-2H- pyridazin-3-one (1). In addition, 3-(4-substituted piperazin-l-ylcarbonyl methyl thio)-6-(thien-2-yl) pyridazines (6a-c) and 3-[2-(4-substitutedpiperazin-1-ylcarbonyl ethylthio]-6-(thien-2-yl) pyridazines (7a,b) were synthesized. Furthermore, 5-(4-substituted piperazin-l-ylmethyl)-6-(thien-2-yl)-2H-pyridazin-3-ones (12a,b) were prepared. The structures of the new compounds were confirmed by elemental analysis as well as by 1H-NMR, IR and MS data. Some of the newly prepared compounds were subjected to evaluation for their anti-inflammatory activity against carrageenan-induced paw edema at a dose of 10 mg/kg using indomethacin as the reference standard.     

Microwave-assisted solvent-free synthesis of 3-[(4-substituted piperazin-1-yl)alkyl] imidazo[2,1-b][1,3]benzothiazol-2(3H)-ones as serotonin3 (5-HT3) receptor antagonists

A series of novel 3-[(4-substituted piperazin-1-yl)alkyl]imidazo[2,1-b][1,3]benzothiazol-2(3H)-ones were prepared by microwave irradiation using alumina as solid support and also by a conventional method. The compounds were characterized by spectral data and the purity was ascertained by microanalysis. The synthesized compounds were evaluated for 5-hydroxytryptamine3 antagonisms in a longitudinal muscle-myenteric plexus preparation from guinea pig ileum against the 5-hydroxytryptamine3 agonist, 2-methyl-5-hydroxytryptamine. Among the test compounds, 3-[2-(4-methylpiperazin-1-yl)ethyl]imidazo[2,1-b][1,3]benzothiazol-2(3H)-one (3b) showed most favorable 5-hydroxytryptamine3 antagonism (pA2 6.7) in the isolated guinea pig ileum.     

Synthesis of biologically active 1'-(2-oxo-2H-benzopyran-6-yl)- 5'-hydroxy-2'-methylindole-3'-amido-2"-phenyl-thiazolidene-4"-ones

6-Aminocoumarins on refluxing with ethyl acetoacetate in 1,2-dichloroethane gave two products: 3'-(2-oxo-2H-benzopyran-6-yl-amino)-but-2'-enoic acid ethyl ester 2a-c and N-(-2-oxo-2H-benzopyran-6-yl)-3'-oxo-butyramide 3a-c. Compounds 2a-c on treatment with 1,4-benzoquinone in N2-atmosphere yielded 1'-( 2-oxo-2H-benzopyran-6-yl)-5'-hydroxy-2'-methyl-3'-carbethoxyindoles 4a-c, which on further treatment with hydrazine hydrate gave 1'-(2-oxo-2H-benzopyran-6-yl)-5'-hydroxy-2'-methylindole-3'-acid hydrazides 5a-c. These acid hydrazides were treated with benzaldehyde to give 1'-(2-oxo-2H-benzopyran-6-yl)-5'-hydroxy-2'-methylindole-3'-benzylidene hydrazides 6a-c, which on further treatment with mercaptoacetic acid in 1,4-dioxane yielded 1'-(2-oxo-2H-benzopyran-6-yl)-5'-hydroxy-2'-methylindole-3'-amido-2"-phenylthiazolidene-4"-ones 7a-c. The structures of the compounds have been established on the basis of spectral and analytical data. All compounds have been screened for their antimicrobial activity and have been found to exhibit significant antibacterial and antifungal activities.     

5-Aryl-1,5-dihydro-2H-1,4-benzodiazepin-2-one derivatives as antianxiety agents.

A new series of 7-chloro- and 7-nitro-5-methoxy-5-phenyl-1,5-dihydro-2H-1,4-benzodiazepin-2-ones (7a, c--e) was synthesized and found to have potent antipentylenetetrazole activity. These compounds were also employed as intermediates in the synthesis of 3-substituted 1,3-dihydro-1,4-benzodiazepin-2-ones (8f--v).