Antipyretic and antioxidant activities of 5-trifluoromethyl-4,5-dihydro-1H-pyrazoles in rats

The objective of this study was to determine the effect of eight 5-hydroxy-5-trifluoromethyl-4,5-dihydro-1H-1-carboxyamidepyrazoles (TFDPs) on rat body temperature and baker’s yeast-induced fever. TFDPs or vehicle (5 percent Tween 80 in 0.9 percent NaCl, 5 mL/kg) were injected subcutaneously and rectal temperature was measured as a function of time in 28-day-old male Wistar rats (N = 5-12 per group). Antipyretic activity was determined in feverish animals injected with baker’s yeast (Saccharomyces cerevisiae suspension, 0.135 mg/kg, 10 mL/kg, ip). 3-Ethyl- and 3-propyl-TFDP (140 and 200 μmol/kg, respectively, 4 h after yeast injection) attenuated baker’s yeast-induced fever by 61 and 82 percent, respectively. These two effective antipyretics were selected for subsequent analysis of putative mechanisms of action. We then determined the effects on cyclooxygenase-1 and -2 (COX-1 and COX-2) activities on 1,1-diphenyl-2-picrylhydrazyl (DPPH) oxidation in vitro, on tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels and on leukocyte counts in the washes of peritoneal cavities of rats injected with baker’s yeast. While 3-ethyl- and 3-propyl-TFDP did not reduce baker’s yeast-induced increases of IL-1β or TNF-α levels, 3-ethyl-TFDP caused a 42 percent reduction in peritoneal leukocyte count. 3-Ethyl- and 3-propyl-TFDP did not alter COX-1 or COX-2 activities in vitro, but presented antioxidant activity in the DPPH assay with an IC50 of 39 mM (25-62) and 163 mM (136-196), respectively. The data indicate that mechanisms of action of these two novel antipyretic pyrazole derivatives do not involve the classic inhibition of the COX pathway or pyrogenic cytokine release.

Synthesis of some new 3-[3-[4'-methoxy benzenesulfonamido] phenyl]-5-[substituted phenyl]-2-pyrazolines, its derivatives and anthelmintic activity

The compounds containing heterocyclic moiety played an important role in the field of medicine and agriculture. It makes possible research upgrading the synthesis, modification and changes in structure of heterocyclic compounds. The pyrazolines have their own importance in heterocyclic compounds due to valuable biological activities. The chemistry of chalcones has generated a lot of scientific studies with special reference to biological applications such as anti-ulcer, antitumour, antitubercular, antidepressant and fungicidal activities. Literature survey indicates that pyrazolines have not been prepared from sulfamino and ethereal linkaging containing chalcones. In the present work para-methoxy benzenesulphonil chloride reacts with metaminoacetophenone to form 3[4'-methoxybenzenesulfonamido] acetophenone [I]. In second step acetophenone [I] reacts with different aromatic aldehyde to form chalcones [II a-c]. In third step chalcones are cyclized with hydrazine hydrate, phenylhydrazine and 2,4-dinitrophenyl hydrazine to form new substituted-2-pyrazolinesI[1-16]. The structures of newly synthesized compounds are confirmed by elemental analysis, IR and p-NMR spectral studies. The synthesized compounds are screened for their anthelmintic activity

Rational design, synthesis and computational structure-activity relationship of novel 3-[4-chlorophenyl]-5-[3-hydroxy-4-ethoxyphenyl]-4,5-dihydro-1H-pyrazole-1-carboxamide

Densely functionalized 3-[4-chlorophenyl]-5-[3-hydroxy-4-etoxyphenyl]-4, 5-dihydro-1H- pyrazole-1- carboxamide was synthesized in an expedient manner through specification and transamidation respectively, of ester-functionalized pyrazoles. This synthetic protocol allowed for three diversifying steps in which appendages on the pyrazole scaffold were adjusted to optimize inhibition of protein kinases. Computational design and study of novel 3-[4- chlorophenyl]-5-[3hydroxy-4-etoxyphenyl]-4, 5-dihydro-1H-pyrazole-1-carboxamide is reported. This computational prediction analysis will improve the understanding of candidate drugs and help in identifying its properties and effects on the human body. Simulation analysis of candidate drugs is necessary for providing clues about regulatory mechanisms, biochemical pathways and broader drug functions

Pharmacological activities of pyrazole and its derivatives

Since a very long time the usefulness and great therapeutic value of pyrazole nucleus has been recognized and the wide range of activities of this nucleus evaluated. However antipyrine was the first synthetic organic compound having pyrazolin-5-one nucleus, to find use as an important drug. Phenylbutazone a prototype of pyrazolidinedione is very potent anti-inflammatory agent but its use is now banned in some countries. Later on many modifications of pyrazole nucleus were attempted and several compounds have been synthesized which serve as basis for treatment of different diseases, like-inflammation, pain, cancer, tuberculosis and disease caused by bacteria. COX-2 inhibitory activities of pyrazoles are well proved and many compounds containing pyrazole nucleus like Celecoxib, Sulphenazole, Sulphinpyrazole and Analgin are well established in the market. The discovery of natural 4-Hydroxy Pyrazole C-glycoside antibiotic pyrazofurin; 4-hydroxy-3beta-D-ribofuronasyl-IH-pyrazole-5-carboxamide; has provided a basis for more rational design and synthesis of new pyrazoles as potential antimicrobial, antiviral, anticancer agents

Synthesis, antimicrobial and anti-inflammatory activities of some new N-substituted sulphonyl indole-3-heterocyclic derivatives

A series of I-substituted sulfonyl indole -3-pyrazolines [4a-j and 5-a-j] and isoxazolines [6a-j] were prepared and tested for their antimicrobial and anti-inflammatory activities. The preparation of compounds 4-6a-j was achieved by treatment of the corresponding chalcones 3a-j with hydrazine hydrate in absolute ethanol, hydrazine hydrate in the presence of glacial acetic acid, and with hydroxylamine hydrochloride in absolute ethanol. The purified products were screened for their antimicrobial activity towards Gram positive, Gram negative bacteria and fungi and also for their anti-inflammatory activity using the carrageenan-induced rat paw oedema. Evaluation of the compounds revealed remarkable antibacterial activity reflected by their ability to inhibit Gram positive and Gram negative bacteria, and also revealed remarkable anti-inflammatory activity reflected by their ability to reduce the carrageenan-induced inflammation in rats

Synthesis of some new 2-[[E]-2-furan-2-yl-vinyl]- 3H- quinazolin-4-one derivatives of expected biological activity

A new series of 2-[[E]-2-furan-2-yl-vinyl]-3H-quinazolin-4-ones incorporated into diverse N, O and S heterocyclic moieties of bioavailability as.5-oxo-4,5-dihydropyrazole 4, 3,5-dimethylpyrazole 5, 5-mercapto-1,2,4-triazole 6, substituted thiazolidinones 8 and 1,3,4-thiadiazole 10, were synthesized by cyclization of the starting quinazolinone acid hydrazide 3 or the acid hydrazide Schiff bases 7 using ethyl acetoacetate, acety I acetone, ammoniumthiocyanate, thioglycolic acid and/or phosphorus pentasulphide, respectively. Other related derivatives such as quinazoline thiosemi - carbazides II and 1,3,4-oxadiazoles 12 were also synthesized. The acid hydrazide 3 showed moderate antimicrobial activity While the starting benzoic acid ethyl ester 2 showed promising anti-inflammatory activity but has no effect on liver carcinoma [HePG2] or brain carcinoma [U251] cell lines

Photochemical synthesis and antimicrobial activities of 1 -phenyl-3-[2-thienyl]-pyrazoline derivatives

Irradiation of 2-phenyl-5-[2-thienyi]-tetrazole 1 with acrylate derivatives 2A-E [molar ratio 1:1] in anhydrous benzene gave the corresponding title compounds 1-phenyl-3-[2-thienyl]-pyrazoline derivatives 4A-E as end products. The mechanism and the regiochemistry of the studied reactions are discussed

A pyrazolyl-thiazole derivative causes antinociception in mice

The present study investigates the antinociceptive effect of the pyrazolyl-thiazole derivative 2-(5-trichloromethyl-5-hydroxy-3-phenyl-4,5-dihydro-1 H-pyrazol-1-yl)-4-(4-bromophenyl)-5-methylthiazole (B50) in mice. Male albino Swiss mice (30-40 g) were used in the acetic acid-induced abdominal writhes and tail-immersion tests. B50 caused dose-dependent antinociception (8, 23 and 80 µmol/kg, sc) in the acetic acid writhing assay (number of writhes: vehicle: 27.69 ± 6.15; B50 (8 µmol/kg): 16.92 ± 3.84; B50 (23 µmol/kg): 13.85 ± 3.84; B50 (80 µmol/kg): 9.54 ± 3.08; data are reported as means ± SEM for 9 animals per group). On the other hand, B50 did not cause antinociception in the tail immersion assay. Naloxone (2.75 µmol/kg, sc) prevented B50-induced antinociception (number of writhes: vehicle-saline: 31.11 ± 3.15; vehicle-naloxone: 27.41 ± 3.70; B50 (80 µmol/kg)-saline: 8.70 ± 3.33; B50 (80 µmol/kg)-naloxone: 31.84 ± 4.26; morphine-saline: 2.04 ± 3.52; morphine-naloxone: 21.11 ± 4.26; 8-9 animals per group). The removal of the methyl group of the thiazole ring of B50 or substitution of the bromo substituent with the methyl at position 4 of the phenyl group, which is attached to the thiazole ring of B50, resulted in loss of activity, suggesting that these substituents are important for antinociceptive activity. B50 had no effect on spontaneous locomotion or rotarod performance, indicating that the antinociceptive effect of B50 is not related to nonspecific motor effects. The antinociceptive profile of B50 seems to be closer to nonsteroidal anti-inflammatory drugs than to classic opioid agents, since it had no analgesic effect in a thermally motivated test.

Some reactions of 3-methyl- 1- phenyl-4- [phenylamino-thiocarbonyl] -2- pyrazolin-5-one

The title compound 1 was prepared via reaction of 3-methyl-1-phenyl-2-pyrazolin-5-one with phenylisothiocyanate. Then, it was converted to pyrazolopyrazole, pyrazolopyrimidine, pyrazolopyridine, and the amino derivatives through reaction with hydrazines, urea, thiourea, malononitrile and aromatic amines. Compound [1] prepared via addition of activated nucleophilic carbon of 3-methyl-1-phenyl-2-pyrazolin-5-one to the electrophilic carbon of phenylisothiocyanate seemed to be suitable to annulation through its reactive center. The reaction of [1] with hydrazine hydrate and phenyl-hydrazine in boiling ethanol gave the pyrazolopyrazole derivatives [2a] and [2b], respectively. The mass spectrum of [2a] showed the parent ion peak at m/z 289 and the following abundant peaks 185, 105, 91, 77, and 51. Structure of [2a] was further established by its reaction with ethyl bromoacetate to give [3]. The latter afforded the hydrazide derivative [4] on reaction with hydrazine hydrate

New synthesis of some 1,8 naphthyridines of possible antimicrobial activity

Some new 2,7-dimethyl-4-[p-[5-aryl-2-pyrazolin-3-yl] anilino] 1, 8-naphthyridines [4a-d] and other related products of the isoxazolines [5a-d] and the pyrimidines [6a-d] were synthesized for the purpose of antimicrobial evaluation. Some representative examples of 4b,c, 5a and 6a showed moderate activity against the growth of Bacillus subtilis, Staphylococcus aureus and Aspergillus niger

Synthesis of some novel benzimidazole derivatives as antimicrobial agents

Synthesis of 2-[p-[5-aryl-1-[H or phenyl]-delta2 pyrazolin-3-yl] anilino] benzimidazoles [4a, b], 2-[p-aryl-2-isoxazolin-3-yl] anilino] benzimidazole [5], 2-[p-[6-aryl-2-[oxo or thioxo]-1,2,5,6- tetrahydropyrimidin-4-yl] anilino] benzimidazoles [6a,b] and 2-[p- sulfamoylanilino] benzimidazoles [7a-g] were synthesized. The new compounds showed inhibitory effect against the growth of Gram +ve, Gram -ve bacteria, yeast and fungi

Synthesis and spectral studies of some new pyrazolines and pyrazoles

A number of 3' -[3-aryl-2-methyl] pyrrol-5-yll-l' - aryl-2 propen-l'-ones 4-13 have been prepared and transformed into the corresponding arylhydrazones 14-28. These hydrazones were cyclized to the pyrazolines 29-43, which were oxidized to the corresponding pyrazoles 49-53. In addition, heating of the pyrazoline 42 with hydrazine hydrate afforded the hydrazide 46 while pyrazolines 41 and 42 gave the acids 47 and 48 upon hydrolysis. Spectral properties of the prepared compounds were discussed

Synthesis and reactions of 3-substituted-2-methyl-5-furfural-acetone and ethyl-2,4-dioxo-6- [3'-Ethoxy carbonyl-2'methyl-furan-5'-yl] hex-5-enoate

3-Ethoxycarbonyl-2-methyl-5-furfuralacetone and the 3-acetyl analogue have been prepared. Their reactions with acyl and arylhydrazines and isomerisation of the prepared hydrazones to pyrazolines was carried out, which were converted to the corresponding brominated pyrazole derivatives by the action of bromine-water. In addition, ethyl-2, 4-dioxo-6-[3-ethoxycarbonyl-2-methylfuran-5-yl]hex-5-enoate was prepared and reacted with hydrazines to afford the corresponding pyrazole 3-esters. The structure of the newly prepared compounds was confirmed by, elemental analysis, Hnmr, uv and ir spectra

Antinociceptive property of new 4-acyl-arylhydrazone pyrazole compounds

A series of new 4-acyl-arylhydrazone pyrazole compunds were tested for antinociceptive activity using the inhibition of abdominal contortions induced by acetylcholine (4 mg/Kg, ip) in the mouse. Dipyrone was used for comparison of the antinociceptive potency of the compounds being tested. All drugs wee administered po in saline (dipyrone) or in propylene flycol 94-acyl-arylhydrazones). The maximum response induced by dipyrone (86% inhibition) was assigned an efficacy index of 1.0. Although none of the compounds had an efficacy index greater than 1.0, all three reached 1.0. The two most potent compounds, Wd1 and W1g, which also had an efficacy similar to that of dipyrone, contain a p-N(CH3)2 and m-OH,p-OCH3 group in the aromatic ring of the acyl-hydrazone, respectively. W1d presented the lowest antinociceptive ED50 in the series (1.41 mg/Kg) and was eleven times more potent than dypyrone (ED50 = 15.80 mg/Kg). Other substitutions at the para position had lower potency than W1d. The present results indicate that the introduction of a group at the para postion of the acyl-arylhydrazone ring increases the antinociceptive activity of these compounds to provide compounds of the same efficacy but greater potency than dipyrone to which these new compounds ara structurally related. Other assays of nociceptive activity are veing used to characterize the mechanism of action of the potential new drugs