Synthesis, characterization and analgesic activity of new 4-arylhydrazono-3-methoxymethyl-2-pyrazolin-5-ones.

New 4-arylhydrazono-3-methoxymethyl-2-pyrazolin-5-ones (5a-j) and 4-arylhydrazono-3-methoxymethyl-1-phenyl-2-pyrazolin-5-ones (6a-j) were synthesized by the reaction of ten novel methyl 2-arylhydrazono-4-methoxy-3-oxobutanoates (4a-j) with hydrazine hydrate and phenylhydrazine, respectively. Treatment of 5a with acetic anhydride yielded 1-acetyl-4-arylhydrazono-3-methoxymethyl-2-pyrazolin-5-one (7). The structures of the tautomerically dynamic compounds were established by spectral data (IR, 1H-NMR, 13C-NMR, EIMS and CIMS) and elemental analysis. The analgesic activity of the title compounds was determined by the modified Koster's test. The most active compound was 4-[(4-chlorophenyl)hydrazono]-3-methoxymethyl-1-phenyl-2-pyrazolin-5-one (6c) demonstrating twice the activity (60%) exerted by the reference drug acetylsalicylic acid (ASA, 27%). The majority of the tested compounds were found to be more effective than ASA.

Synthesis and antimicrobial activity of new 6-phenylimidazo[2,1-b]thiazole derivatives.

A series of new N2-substituted-6-phenylimidazo[2,1-b]thiazole-3-acetic acid hydrazides (2a-j) were synthesized and evaluated for in vitro antimicrobial activity against various bacteria and fungi. Some of the compounds showed antimicrobial activity against Staphylococcus aureus ATCC 6538, Staphylococcus epidermidis ATCC 12228, Trichophyton mentagrophytes var. Erinacei NCPF-375, Trichophyton rubrum and Microsporum audounii (MIC 25-0.24 micrograms/ml). The in vitro antimycobacterial activity of the new compounds was also investigated. The compounds exhibited different degrees of inhibition (17.98%) against Mycobacterium tuberculosis H37Rv in the primary screen that was conducted at 12.5 micrograms/ml using the BACTEC 460 radiometric system.

Synthesis and preliminary evaluation of new 5-pyrazolinone derivatives as analgesic agents.

New 4-(aroyloxyalkanoyl)-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one s (5) were cyclized to 4-(2-aryl-5-unsubstituted/substituted oxazol-4-yl)-2,3-dimethyl-1-phenyl-3-pyrazolin-5-ones (6) employing the Davidson procedure. Preliminary evaluation of analgesic activity revealed that the effect of 4-(2-phenyl-5-ethyloxazol-4-yl)-2, 3-dimethyl-1-phenyl-3-pyrazolin-5-one and 4-[2-(4-chlorophenyl)-5-ethyloxazol-4-yl]-2, 3-dimethyl-1-phenyl-3-pyrazoline-5-one on acetic acid induced writhing was superior to that of antypyrine and aminopyrine. 4-[2-(4-Chlorophenyl)-5-methyloxazol-4-yl]-2, 3-dimethyl-1-phenyl-3-pyrazolin-5-one and 4-[2-(4-methoxyphenyl)-5-ethyloxazol-4-yl]-2, 3-dimethyl-1-phenyl-3-pyrazolin-5-one were more potent than aminopyrine, whereas 4-(2-phenyl-5-methyloxazol-4-yl)-2, 3-dimethyl-1-phenyl-3-pyrazolin-5-one and 4-[2-(4-methoxyphenyl)-5-methyl-oxazol-4-yl]-2, 3-dimethyl-1-phenyl-3-pyrazolin-5-one were not as active (modified Koster's Test; 0.19-0.21 mmol.kg(-1)). None of the selected entries showed inhibition of formaldehyde-induced paw oedema.

Synthesis and hypnotic activity of new 4-thiazolidinone and 2-thioxo-4,5-imidazolidinedione derivatives.

Conveniently accessible 4-[(2-(3,4-dimethoxyphenyl)ethyl]-3-thiosemicarbazide (2) was converted to new 1-substituted benzylidene/furfurylidene-4- [2-(3,4-dimethoxyphenyl)ethyl]-3-thiosemicarbazides (3) which furnished 2-(substituted benzylidene/furfurylidene) hydrazono-3-[2-(3,4-dimethoxyphenyl)ethyl]thiazolidin-4-ones (4) and 1-(substituted benzylidene/furfurylidene)-amino -3-[2-(3,4-dimethoxyphenyl)ethyl]-2-thioxo-4,5-imidazolidinedio nes (5) on reaction with chloroacetic acid and oxalyl chloride, respectively. The structure of 5 was confirmed by X-ray diffraction studies performed on 5a. 4 and 5 were evaluated for their potentiating effects on pentobarbital induced hypnosis. Most of the compounds caused remarkable increases in pentobarbital sleeping time.

5-Nitroimidazole derivatives as possible antibacterial and antifungal agents.

Some novel 1-[2-[[5-(2-furanyl)-4-substituted 4H-1,2,4-triazol-3-yl[thio[ethyl[-2-methyl-5-nitro-1H-imidazoles (3), 1-[3-[[5-(2-furanyl/2-thienyl)-4-substituted 4H-1,2,4-triazol-3-yl[-thio]-2-hydroxypropyl[-2-methyl-5-nitro-1H- imidazoles (5) and 1-[3-[(N,N-disubstituted thiocarbamoyl)-thio[-2-hydroxypropyl]-2-methyl-5-nitro-1H-imidazoles (7) were synthesized and evaluated for in vitro antibacterial and antifungal activity. Some of 5 were found to be effective against bacteria and fungi (minimum inhibitory concentration (MIC) 7.3-125 micrograms/ml), whereas 7 were found to be effective against fungi (MIC 3-25 micrograms/ml).

Synthesis and anticonvulsant activity of new 3-[(2-furyl)carbonyl]amino-4-thiazolidinone and 2-[(2-furyl)carbonyl]hydrazono-4-thiazoline derivatives.

A series of new 2-aryl-3-[(2-furyl)carbonyl]amino-5-nonsubstituted/methyl-4-thi azolidinones (3) and 2-[(2-furyl)carbonyl]hydrazono-3-alkyl-4-aryl-4-thiazolines (5) was synthesized and evaluated for anticonvulsant activity against pentylenetetrazole induced seizures. Preliminary results indicated that potency was sensitive to substituents at the 2 and 5 positions of the 4-thiazolidinone and 3 and 4 positions of the 4-thiazoline rings. Among 3,2-(phenyl)/ (4-fluorophenyl)-3-[(2-furyl)carbonyl]amino-5-methyl-4-thiazolidinone s (3e and 3f) and among 5, 2-[(2-furyl)carbonyl]hydrazono-3-allyl-4-(4-bromophenyl)-4-thiazol ine (5e), showed the highest protection (40%).

Synthesis and antimicrobial properties of new 4-(alkylidene/arylidene)- amino-5-(2-furanyl)-2,4-dihydro-3H-1,2,4-triazole-3-thiones and 6-aryl-3-(2-furanyl)-7H-1,2,4-triazolo[3,4-b][1,3,4]thiadiazines.

A series of 4-(alkylidene/arylidene)amino-5-(2-furanyl)-2,4-dihydro- 3H-1,2,4-triazole-3-thiones (2) and 6-aryl-3-(2-furanyl)-7H-1,2,4-triazolo[3,4-b][1,3,4]thiadiazines (3) were synthesized. The configuration of 2g was assigned on the basis of 1H-NMR data. Of the new derivatives tested, only 2b, 2g, and 4f were found to be active against Staphylococcus aureus and/or Staphylococcus epidermidis (MIC 125-1.95 micrograms/ml), whereas all exhibited varying degrees of antifungal activity (MIC 25-0.8 micrograms/ml).

Synthesis and antimicrobial activity of new tetrahydro-2H-1,3,5-thiadiazine-2-thione derivatives.

A series of 3,5-disubstituted tetrahydro-2H-1,3,5-thiadiazine-2-thiones was synthesized and evaluated for antibacterial and antifungal activity. All of the tested compounds were found active against Staphylococcus aureus and Staphylococcus epidermidis. The compounds were also active against yeast-like fungi and molds where the anticandidal activity of 3a against Candida albicans was superior to the standards miconazole and clotrimazole.

Synthesis and anticonvulsant activity of new 4-thiazolidone and 4-thiazoline derivatives.

A number of 2-(2-furoylhydrazono)-3-substituted 4-thiazolidone and 2-(2-furoylhydrazono)-3,4-disubstituted 4-thiazoline derivatives were synthesized and evaluated for anticonvulsant activity. Most of the tested compounds showed significant activity against MES induced seizures.

Synthesis and anticonvulsant activity of new 4- thiazolidone and 4-thiazoline derivatives.

A number of 2-(2-furoylhydrazono)-3-substituted 4-thiazolidone and 2-(2-furoylhydrazono)-3,4-disubstituted 4-thiazoline derivatives were synthesized and evaluated for anticonvulsant activity. Most of the tested compounds showed significant activity against MES induced seizures.