• YAKHAK HOEJI
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• v.44 no.3
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• pp.272-278
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• 2000

The antiinflammatory mechanism of NSAIDs is attributed to the reduction of prostaglandin synthesis by the direct inhibition of cyclooxygenase. Inhibition of prostaglandin production in organs such as stomach and kidney can result in gastric lesions, nephrotoxicity and increased bleeding. In this study, newly designed COX-2 inhibitors, synthesized 1,2-benzothiazine derivatives, were screened in vitro for selectivity of COX-1 and COX-2 inhibition properties. Lead compounds in the structure-activity relationship were studied to synthesize new highly selective COX-2 inhibitors.13 determine inhibitory effect of COX-2, synthesized 1,2-benzothiazine derivatives were screened with accumulation of prostaglandin by lipopolysaccharide (LPS) in aspirin-treated macrophages and murine macropharge cell. Some of synthesized 1,2-benzothiazine derivatives were shown to be effective as selective COX-2 inhibitory activity. Others exhibited a preferential inhibition of COX-2, although some COX-1 inhibitory activity was still present. As a conclusion, simple monomer derivatives were more active than dimer derivatives. Substitution of halogen (Br, C1) on the benzothiazine nucleus slightly enhanced inhibition activity.

• YAKHAK HOEJI
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• v.46 no.6
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• pp.375-380
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• 2002

In this study, newly designed COX-2 inhibitors, synthetic derivatives of benzothiazine-3-carboxamide, were screened in vitro for selectivity of COX-1 and COX-2 inhibition properties. 7-Bromo-1,2-benzoisothiazine derivatives were obtained from 4-bromotoluene over the chlorosulfonation, amination and oxidation. And benzothiazine ring was synthesized through Gabriel-Colmann rearrangement reaction. To evaluate inhibitory effect of COX-2, synthetic derivatives of benzothiazine-3-carboxamide were tested with accumulation of prostaglandin by lipopolysaccharide in aspirin-treated murine macropharge cell. Some of the synthesized lead compounds have potentially shown the structure-activity relationship for selectivity of COX-2 inhibition activity.

• YAKHAK HOEJI
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• v.41 no.6
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• pp.724-729
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• 1997

New 7-Halo-4-hydroxy-2-allyl-N-3-(4-methoxy-2-carboxylic acid pyrrolidinyl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide derivatives were synthesized through the condensation of 7-halo-4-hydroxy-2-allyl-1,2-benzothiazine-3-carboxylic acid methyl ester 1,1-dioxide with 4-methoxy L-proline.

• Archives of Pharmacal Research
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• v.22 no.1
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• pp.44-47
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• 1999

Three 1,2-benzothiazine derivatives were synthesized, and their analgesic / anti-inflammatory efficacy and their effect s of gastric irritation were evaluated. Among the three compounds, 39 exhibited the most potent anlagesic action, but the effect was weaker than that of piroxicam. Nonetheless, the compound showed 4 times more potent analgesic action with less gastric damage than did ibuprofen. These compounds did not show anti-inflammatory effect at an oral dose of 5 mg/kg.

• Archives of Pharmacal Research
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• v.15 no.3
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• pp.251-255
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• 1992

A number of 4-hydroxy-2H (or alkyl)-N-(3-aralkyl-2-thio-1-hydantoinyl)-1, 2-benzothiazine3-carboxamide 1, 1-dioxides were synthesized through the reaction of 4-hydroxy-2H (or alkyl)1, 2-benzothiazine-3-carboxylic methyl ester 1, 1-dioxide and 1-amino-2-thio-3-aralkyl-4-imidazolones in xylene. The compounds synthesized were screened for antinflammatory effect on carrageenin-induced edema in rat and for analgesic effect on acetic acid-induced Writhing syndrome in mice. Most compounds were inhibots of carrageenin-induced rat foot edema and some showed significant antinflammatory activity comparable to that of indomethacin and significant analgesic activity comparable to that of indomethacin and aspirin.

• 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.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.344.1-344.1
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• 2002

We report the synthesis of several new 3-aminohydantoinyl-1.2-benzothiazine derivatives and propose an another mechanism of the cyclization to the hydantoins for the development candidates of COX-2 inhibitors. 3-Aminohydantoins 3a-d were prepared through cyclization of the condensation products that were formed by heating amino acids and tert-bytyl carbazate in quinoline according to the method of Lalezari. (omitted)

• Bulletin of the Korean Chemical Society
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• v.23 no.12
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• pp.1836-1838
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• 2002

• Bulletin of the Korean Chemical Society
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• v.21 no.12
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• pp.1249-1250
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• 2000

• Proceedings of the PSK Conference
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• 2000.10a
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• pp.213.3-214
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• 2000