Cyclooxygenase-2 저해제로서의 benzothiazine 유도체 합성과 항염작용 평가

• 영문명: Antiinflammatory Evaluation and Synthesis of Benzothiazine Derivatives as Cyclooxygenase-2 Inhibitor
• 발행기관: 대한약학회
• 저자명: 신혜순(Hea Soon Shin) 박명숙(Myung Sook Park) 권순경(Soon Kyoung Kwon)
• 간행물 정보: 『약학회지』제44권 제3호 (2000년), 272~278쪽, 전체 7쪽
• 주제분류: 의약학 > 기타의약학
• 파일형태: PDF
• 발행일자: 2000.06.29

영문 초록

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. To 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, Cl) on the benzothiazine nucleus slightly enhanced inhibition activity.

키워드

1,2-benzothiazine derivatives antiinflammatory cyclooxygenase.