• YAKHAK HOEJI
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• v.35 no.4
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• pp.314-318
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• 1991

A convenient method for the synthesis of indoprofen, which is a potent antiinflammatory agent, w described. Ethyl $\alpha$-(4-aminophenyl)propionate was prepared by nitration of ethyl $\alpha$-phenylpropionate, followed by reduction. Ethyl $\alpha$-[4-(1, 3-dioxo-2-iso-indolinyl)phenyl]propionate was obtained from condensation reaction of phthatic anhydride and ethyl $\alpha$-(4-aminophenyl)propionate. Indoprofen was prepared by reduction of ethyl $\alpha$-[3-(1, 3-dioxo-2-iso-indolinyl)phenyl]propionate with zinc dust-acetic acid, followed by hydrolysis of the resultant ethyl $\alpha$-[4-(1-oxo-2-iso-indolinyl)pheriyl]propionate.

• YAKHAK HOEJI
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• v.36 no.1
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• pp.12-16
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• 1992

A new method for the synthesis of alminoprofen, which is a non-steroidal antiinflammatory agent, was described. Ethyl 2-phenyl-propionate(4) was prepared by Friedel-Crafts reaction of benzene with ethyl ${\alpha}-chloro-{\alpha}(methylthio)acetate(1)$, followed by methylation and desulfurization of the resultant ethyl 2-(methylthio)phenylacetate(2). Ethyl 2-(p-aminophenyl)propionate(6) was obtained by nitration of (4) and successive reduction of ethyl 2-(p-nitrophenyl)propionate(5). Alminoprofen was synthesized by reaction of (6) with methallyl chloride, followed by hydrolysis of the resultant ethyl 2-(p-methylallylaminophenyl)propionate (7).

• Biomolecules & Therapeutics
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• v.4 no.1
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• pp.32-35
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• 1996

SKI306X is a herbal extract prepared from three herbs Clematis mandshurica, Trichosanthes kirilowii and Prunella vulgaris. It showed strong antiinflammatory actions on carrageenan-induced edema, acetic acid-induced pain, adjuvant-induced arthritis, and oxygen radical-generated reactions. In this study, the acute toxicity of SKI306X was evaluated in rats by a single oral administration. Thirty male and thirty female rats were divided into 6 groups according to the dose levels, respectively. After oral administration of SKI306X with several doses (5.0 g/kg, 3.3 g/kg, 2.2 g/kg, 1.5 g/kg, 1.0 g/kg), mortality, clinical signs, body weight, and gross findings in organs were examined. No toxic effect was shown in terms of mortality, clinical signs, body weight changes and gross findings. It is suggested the LD$_{50}$ of SKI306X would be more than 5.0 g/kg in rats.s.

• Biomolecules & Therapeutics
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• v.6 no.4
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• pp.417-422
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• 1998

Loxoprofen sodium (sodium 2-[4-(2-oxocyclopentylmethyl)phenyl] propionate dehydrate) is a nonsteroidal antiinflammatory drug of $\alpha$-phenyl propionic acid derivative. To test the bioequivalence of loxoprofen, the pharmacokinetic parameters of new preparation of loxoprofen, LENOX was compared with LOXONIN as a reference drug. Fourteen healthy volunteers were entered to the stydy (Yonsei University College of Medicine, Severance Hospital IRB approval No. 9608). They were administered 60 mg of loxoprofen in 2$\times$2 cross-over design. There was one week of drug-free interval between doses. The blood sample was taken on schedule up to 8 hours, and the plasma concentration loxoprofen was measured by reverse phase high-performance liquid chromatography (HPLC) with UV-detector. There were no significant difference between two preparations when AUC, Cmax, and Tmax were compared by ANOVA. The mean differences of AUC, Cmax, and Tmax were within 20% of the reference drug: the values were 2.22,5.61, and 12.50%, respectively. The confidence limits of AUC and Cmax but not Tmax satisfied the bioequivalence criteria. These results suggest that the tested LENOX is bioequivalent to the reference drug.

• Natural Product Sciences
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• v.5 no.4
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• pp.155-158
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• 1999

Several biological activities of extracts from roots of Cichorium intybus Linne (Compositae) were studied in this paper. The antiinflammatory activity of the methanol extract of this root was investigated against carrageenin induced edema in rat‘s hind paw. Significant inhibitory effects were observed at the dose of 1,000 mg/kg and were compared with aspirin as a control. The hepatoprotective activities of the methanol extract, ethylacetate and butanol fraction were studied on mice whose livers are damaged by $CCl_4$. The serum transaminase activities (ALT, AST) were reduced at the dose of 1,000 mg/kg of the methanol extract, 500 mg/kg of ethylacetate and butanol fraction, respectively. The bile juice secretion was also increased significantly from each fraction. The antidiabetic activity was examined on strepto-zotocin-induced diabetic rats with methanol extract. Methanol extract gave a significant reduction of blood glucose levels in 1 week and 3 weeks.

• Journal of Pharmaceutical Investigation
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• v.26 no.3
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• pp.155-168
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• 1996

The active site of cyclooxygenase was modeled by complementary receptor-cavity mapping procedure using 3D structures of the non-steroidal antiinflammatory drugs (NSAIDs). A total of 50 NSAIDs were chosen as data ligands which compete the same site on the enzyme. Partial atomic charges were estimated, and the energetic differences for various conformations were calculated so as to meet the need for a most efficient overlapping of the probably-equivalent functional groups of the ligand molecules. The structure activity relationships of the NSAIDs, if available, were fully considered throughout the modeling. The overall shape of the model obtained is similar to a boot-without-bottom. Most of inner surface of the cavity appeared as hydrophobic; two polar counterparts except the carboxyl-binding position were found. By this model, some clear explanations could be given on the experimental observations which were not satisfiably understood yet.

• YAKHAK HOEJI
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• v.26 no.2
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• pp.97-103
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• 1982

This paper presents anti-inflammatory effects of nonsteroidal anti-inflammatory drugs and their copper complexes, and the change of content of copper in serum, liver, brain and edema foot induced by 1% carrageenan in rats, and also investigation of stomach hemorrhage. The results were as follows. 1. The content of copper decreased in liver and brain, however, the concentration of copper significantly increased in serum and edema site after carrageenan injection in rats. 2. The content of copper in serum and edema site was decreased after administration of anti-inflammatory drugs. 3. Edema inhibition rate of aspirin was, higher than that of copper (II) aspirinate, but edema inhibition rate of copper complex of naproxen was markedly higher than that of naproxen. 4. Hemorrhage of stomach of copper salicylate was higher than that of sodium salicylate, but hemorrhage of stomach of sodium naproxen was higher than that of copper naproxen.

• YAKHAK HOEJI
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• v.35 no.5
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• pp.389-393
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• 1991

A convenient method for the synthesis of indobufen, which is a potent antiinflammatory agent, was described. Ethyl 2-phenylbutyrate(4) was prepared by Friedel-Crafts reaction of benzene with ethyl $\alpha$-chloro-$\alpha$-(methylthio)acetate(l) followed by ethylation and desulfurization of the resultant ethyl 2-(methylthio)phenylacetate(2). Ethyl 2-(p-aminophenyl)butyrate(6) was prepared by nitration of (4) and successive reduction of ethyl 2-(p-nitrophenyl) butyrate(5). Indobufen was obtained by condensation reaction of (6) with phthalic anhydride followed by reduction and hydrolysis of the resultant ethyl 2-[p-(1, 3-dioxo-2-isoindolinyl)phenyl]butyrate(7).

• Archives of Pharmacal Research
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• v.17 no.3
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• pp.175-181
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• 1994

The solid-phase extraction (SPF) with subsequent tert-butyldimethylsilyl (TBDMS) derivatization was investigated for the rapid profiling and screening of various carboxylated non-steroidal antiinflammatory drugs (NSAIDs) simultaneously in biological fluid samples. Compared to the conventional SPF in adsorption mode using Chromosorb 102, Chromosorb 107, Carbopak B and Thermosorb, the SPF in partition mode using Chromosorb P as the adsorbent, and ethyl acetate/methylene chloride as the eluting solvents provided hightest overall recovenies of the NSAIDs from aqueous solutions with good precision. The solid-phase extracted NASIDs were silylated with N-methyl-N-(tert-butyldimethylsily)trifuoroacetamide to TBDMS derivatives and directly analyzed by capillary gas chromatography and gs chromatography-mass spectrometry. The usefulness of the present method was examined for the profilling and screening of saliva, serum and urine samples for various NSAIDs simultaneously.

• Archives of Pharmacal Research
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• v.19 no.2
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• pp.148-152
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• 1996

The efficient synthesis of 4-(2-thiazolyloxy)phenylalkanoic acids (10a-c), which are a potent antiinflammatory agent, was achieved in 5-6 steps starting from isopropoxybenzene and methyl $\alpha-chloro-\alpha-(methylthio)acetate (1)$. The key intermediate (4) was prepared by Friedel-Crafts reaction of isopropoxybenzene with (1) followed by desulfurization and the removal of isopropyl protector. Methyl 4-hydroxyphenylalkanoates (6, 8) were similarly obtained from alkylation of (3) and deprotection.