Synthesis of new salicylamide derivatives with evaluation of their antiinflammatory, analgesic and antipyretic activities

A new series of pyridazine, pyrazoles, pyrazolidine-3,5-dione, Semicarbazide, thiosemicarbazides, hydantoin, thiohydantoins, 1,2,4-triazoles, S-triazolo[3,4-b]-1,3,4-thiadiazoles incorporated indirectly into salicylamide moiety at position 2 were synthesized. Also the synthesis of novel series of 3-salicylamido-2-hydroxypropyl-amine derivatives were prepared. Several of these compounds were screened for antiinflammatory, analgesic, antipyretic and ulcerogenic activities.     

Synthesis of some 2-benzoxazolinone derivatives and their analgesic properties

In this study, eight new 1-(2-benzoxazolinone-6-yl)-2-(4-arylpiperazine-1-yl)ethanol and -propanol derivatives have been prepared. Their structures have been elucidated by IR- and 1H-NMR-spectra and by elementary analysis. The analgesic activities of these compounds, using modified Koster's test have been investigated. 1-(5-Chloro-3-methyl-2-benzoxazolone-6-yl)-2-[4-(2-methoxyphenyl)p iperazine-1- yl]ethanol has been found more active than O-acetyl-salicylic acid, respectively.     

Synthesis, analgesic and antipyretic activity of 2-(antipyrin-4-yl)hydrazones of 1,2,3-triketones and their derivatives

1,2,3-Triketone 2-(antipyrin-4-yl)hydrazones were synthesized via the azo-coupling reactions of 1,3-diketones with 2-(antipyrin-4-yl)diazonium chloride. The fluoroalkyl-containing hetarylhydrazone enters into cyclocondensation with hydrazines at the 1,3-dicarbonyl fragment to yield 3-tetrafluoroethyl derivatives of pyrazole. It was found that 1,2,3-triketone 2-(antipyrin-4-yl)hydrazones and N-(2-hydroxyethyl)-substituted pyrazole exhibit analgesic activity comparable with that of their structural analog analgin (metamizole sodium), but do not possess antipyretic properties. In contrast, N-phenyl-substituted pyrazole did not exhibit analgesic properties but produced a certain antipyretic effect four hours after pyrogenic administration. Fluoroalkyl-containing compounds are less toxic substances than nonfluorinated 2-(antipyrin-4-yl)hydrazone and analgin. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 40, No. 7, pp. 27 ‣ 29, July, 2006.     

Synthesis and properties of 1,4-benzodiketo- and 1,4-benzomono-ketodicarboxylic acids and their derivatives

Translated from Khimiko-farmatsevitcheskii Zhurnal, Vol. 25, No. 7, pp. 56–59, July, 1991.     

Synthesis and analgesic and antiinflammatory properties of new benzodiazepine derivatives

Several new N-(2,3-dihydro-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3-yl)-2-carboxamides have been synthesized and characterized with respect to acute toxicity (LD₅₀), analgesic and antiinflammatory properties (formalin-and carrageenan-induced foot edema models), and interaction with morphine-induced antinociception in mice. The new compounds were prepared by acyl coupling of 2-aminobenzophenones with α-(benzotriazol-1-yl)-N-acylglycines followed by displacement of the benzotriazole ring with ammonia and cyclization of the resulting monoacyl aminals. The LD₅₀ of the synthesized compounds exceeds 1000 mg/kg. Three compounds produced significant analgesic action in doses 100–150 μg/kg in the early (painful) phase of the formalin test and potentiated the morphine-induced antinociception in this test. The synthesized drugs neither showed antinociception in the second (inflammatory) phase of the formalin test nor decreased the carrageenan-induced foot edema growth. Thus, the synthesized compounds produce analgesic action but do not possess antiinflammatory properties. The analgesic activity is probably due to the interaction with μ-and δ-opioid receptors. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 39, No. 12, pp. 21–23, December, 2005.     

Preliminary studies on antipyretic and analgesic properties of Taverniera abyssinica

In an attempt to ascertain the pharmacological basis of the use of the marketed traditional drug Taverniera abyssinica A. Rich. (Amharic name Dingetegna), crude extracts as well as purified substances of this plant were tested for their antipyretic and analgesic properties. Antipyretic activity was determined on rats made hyperthermic by yeast injection and analgesic activity was determined by the hot plate, as well as the acetic acid induced writhing, methods. The study showed that the plant possesses significant antipyretic and analgesic activities.     

Synthesis and analgesic properties of N-phosphorylated derivatives of Phe-Ala and Phe-Gly

N-Phosphoryl dipeptides derived from Phe-Ala, Phe-Ala-NH₂ and Phe-Gly-NH₂ were synthesized and their analgesic activity was evaluated in mice. Intracere-broventricular administration of P-Phe-Ala-NH₂ produced a 100-fold increase in the analgesic potency of Phe-Ala and led to a potentiation and prolongation of the analgesic effect of the exogenously administered Met-enkephalin.     

Anti-inflammatory, analgesic and antipyretic activity of pyrimidant

In experiments on rats with different models of pathology it was demonstrated that a new non-steroidal anti-inflammatory drug pyrimidant exerts pronounced anti-inflammatory, analgesic and antipyretic effects. In some cases its activity exceeds that of indomethacin, brufen, butadione, mefenamic acid, sodium salicylate.     

赖氨匹林的解热、镇痛和抗炎作用

目的：应用大鼠及小鼠研究赖氨匹林的抗炎、镇痛及解热作用。方法：用大鼠足跖肿胀研究抗炎作用，用小鼠醋酸扭体法及热板法测定镇痛作用，用鲜酵母法测定解热作用。结果：赖氨匹林对大鼠足跖肿胀有明显抑制作用，最大抑制率为８０％（Ｐ＜０．０１）。小鼠醋酸扭体法测得镇痛ＥＤ５０＝７２±２３ｍｇ／ｋｇ，对鲜酵母致大鼠体温升高有明显抑制作用。小鼠半数致胃溃疡剂量ＵＤ５０＝０．１８±０．０６ｍｍｏｌ／ｋｇ，是阿司匹林的２．４倍。结论：赖氨匹林具有和阿司匹林相当的解热、镇痛和抗炎作用，而对胃肠道的毒副作用比阿司匹林小。