• 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.

• 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.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.11a
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• pp.47-50
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• 1997

Drug development began with the finding of biologically active compounds which are obtained by chemical synthesis or from natural sources. The advent of Combinatorial Chemistry is recognized as a strategy which has a potential to change the methodology of research and development(R&D) of new drugs. Drug development has been carried out with diverse strategies. In the past several decades a variety of new methodology have been introduced in R&D. Random screening of accumulated synthetic samples which had been synthesized for development of other drugs led to the discovery of new drugs. The typical examples are anti-asthma drug trimethoquinol and calcium antagonist diltiazem. (herbesser). In particular the latter drug has been used as a calcium antagonist worldwide, however it was first synthesized to find new tranquilizer and this is the reason why diltiazem has benzodiazepam skeleton. The random screening contributed in the finding of new drugs were carried out with whole animal test and it is a standard methodology in R&D of new drugs. Aspirin is the first synthetic non-steroidal antiinflammatory drug(NSAID) and has been used for more than one hundred years. It is the first example of drug developed from natural product. Salicin is the main constituent of willow bark which had been used in Europe for a long time to treat arthritis and aspirin was developed from salicin. Most of NSAID used clinically were developed from the structure of aspirin, however it took 70 years to clarify why aspirin exhibits its antiinflammatory, analgesic and antipyretic activities. The target of aspirin is cyclooxygenase(COX)which is the first enzyme involved in arachidonate cascade leading to the production of prostaglandins(PG) and thromboxan(TX). Side effect of aspirin causing ulcer in stomach is rather serious problem, since aspirin is so popular drug easily obtained in drug store(OTP). This problem is now going to be solved by a new finding on COX, which have two different types, one is constitutionally expressed COX 1 in almost all organs and the other is inducible COX 2. COX 2 is the responsible enzyme in inflammation etc and now the search of COX 2 specific inhibitors is the target of R&D of next generation NSAID.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.396.3-397
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• 2002

Because of the differences in biological and pharmacological properties between enantiomers of chiral acidic non-steroidal antiinflammatory drugs (NSAIDs) in human body. accurate determinations of their optical purities have been in great need. Racemic ibuprofen. tiaprofen. suprofen. flubiprofen and napoxen were reacted with (1R. 28. 5R)-(－)-menthol to convert them to corresponding diastereomeric (1R. 2S. 5R)-(－ )-menthyl esters. (omitted)

• Journal of Acupuncture & Meridian Studies
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• v.11 no.6
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• pp.341-342
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• 2018

• Journal of the Korean Society of Food Science and Nutrition
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• v.38 no.10
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• pp.1289-1294
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• 2009

Inflammation is a pivotal component of a variety of diseases, such as atherosclerosis and tumour progression. Various naturally occurring phytochemicals exhibit antiinflammatory activity and are considered to be potential drug candidates against inflammation-related pathological processes. Red pepper is the most consumed species in Korea. However, the antiinflammatory effects of red pepper have not been characterized. Thus, the present study was designed to evaluate the effects of the aqueous extract from red pepper (RPAE) on lipopolysaccharide (LPS)-induced inflammatory responses in murine macrophages. RPAE demonstrated strong antiinflammatory activity through its ability to reduce nitric oxide and prostaglandin $E_2$ production in the LPS-stimulated mouse macrophage cell, RAW264.7. It also inhibited the production of interleukin-6 (IL-6) on the LPS-stimulated RAW264.7 cells. Further study indicated that LPS-stimulated induction of inducible nitric oxide synthase and cyclooxygenase-2 was significantly inhibited by RPAE exposure (1,000 mg/mL) in RAW264.7 cells. Collectively, these data suggest that the use of RPAE may be a useful therapeutic approach to various inflammatory diseases.

• Korean Journal of Pharmacognosy
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• v.8 no.2
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• pp.61-68
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• 1977

The content of micro inorganic compounds in the 145 kinds of crude drugs on market was determined with Model 207 Atomic Absorption Spectrophotometer and Model 306 Flameless A.A. Content of Fe, Cu, Ni, Mn, Cd, Cr, Sn, and Pb was examined and the results revealed that the crude drugs which are using as a hematics and emmenagogues contained high content of iron, and those which are using as a antiinflammatory and emmenagogues contained high content of copper. Aromatic stomachics contain manganese and zinc, and diuretics and antiinaflammatory agents do tin. High content of Ni was found in tonics, but chronium and cadmium were not detected in crude drugs. There were no differences of content of trace metals in the various site of plants used.

• Archives of Pharmacal Research
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• v.20 no.5
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• pp.414-419
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• 1997

Gastrointestinal irritation is the most frequent adverse effect in patients chronically taking nonsteroidal antiinflammatory drugs (NSAIDs) for the treatment of arthritic conditions. Gastroprotective effect of DA-9601, a new antiulcer agent from Artemisiae Herba extract, against NSAID was evaluated in a rat model of arthritis that is similar in many aspects to human rheumatoid arthritis. Daily oral dosing of naproxen (30 mg/kg), one of the most commonly used NSAID, induced apparent gastric lesions as well as a significant decrease in mucosal prostagiandin $E_2;(PGE_2)$ and prostagiandin F_${1{\alpha}}$$(PGF_{1{\alpha}})$ levels. Coadministration of DA-9601 prevents naproxen-induced mucosal injury and depletion of prostaglandins, in a dose-related manner. DA-9601 did not alter the antiinflammatory or analgesic effect of naproxen. The present results suggest that DA-9601 may be useful as a mucoprotectant against NSAIDs in clinical practice.

• Biomolecules & Therapeutics
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• v.9 no.2
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• pp.69-78
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• 2001

Cyclooxygenase (COX) is an enzyme, which catalyzes the production of prostaglandins from arachi-donic acid and exists in two isoforms (COX-1 and COX-2). COX-1 is involved in the maintenance of physiological functions such as platelet aggregation, cytoprotection in the stomach and maintenance of normal kidney function. COX-2 is induced significantly in vivo under inflammatory conditions. COX-1 and COX-2 serve different physiological and pathological functions. All commercially available nonsteroidal antiinflammatory drugs (NSAIDS) are inhibitors of both COX-1 and COX-2. Therefore, selective inhibitors of COX-2 may be effective antiinflammatory agents without the ulcerogenic effects associated with current NSAms. Since the mid 1990s, a number of reports have been appeared on the preparation and biological activity of selective COX-2 inhibitors. Recently celecoxib, and rofecoxib, the representative COX-2 inhibitors, are introduced in the drug market. In this paper the relationship of structure-activity for selective COX-2 inhibitors is reviewed.

• YAKHAK HOEJI
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• v.44 no.6
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• pp.494-498
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• 2000

Noble 7,7'-substituted (or unsubstituted) 4-oxo-1,1',2,2'-dibenzothiazine-3,3'-dicarboxylic acid methyl ester 1,1,1',1'-tetraoxide 3,4'-yl ethers 2a-h were synthesized through the dehydration of 7-substituted (or unsubstituted) 4-hydroxy-1,2-benzothiazine-3-carboxylic acid methyl ester 1,1-dioxides 1a-h using silver(I) oxide for the development of new nonsteroidal antiinflammatory drugs (NSAIDs). Optimal reaction was proceeded through stirring of distilled acetone using 100 mol% of silver(I) oxide at room temperature for 24-68 hrs.