SAR studies of capsazepinoid bronchodilators. Part 1: The importance of the catechol moiety and aspects of the B-ring structure

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• 作者：Marı ; ´ ; a F. Dalence-Guzmá ; n ; Magnus Berglund ; Staffan Skogvall ; Olov Sterner
• 关键词：Capsazepine ; SAR ; A-ring catechol ; B-ring ; Isoindoline ; 1 ; 2 ; 3 ; 4-Tetrahydroisoquinoline ; 2 ; 3 ; 4 ; 5-Tetrahydro-1H-2-azepine ; 2 ; 3 ; 4 ; 5-Tetrahydro-1H-3-benzazepine ; Bronchodilator ; Small human airways ; Asthma ; COPD
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2008
• 出版时间：1 March 2008
• 年：2008
• 卷：16
• 期：5
• 页码：2499-2512
• 全文大小：326 K

文摘

Capsazepine as well as its derivatives and analogues are general inhibitors of constriction of human small airways. From a systematic variation of the capsazepine structure, divided into four regions, SARs were established. This part concerns the catechol moiety of the A-ring as well as the 2,3,4,5-tetrahydro-1H-2-azepine moiety (the B-ring) of capsazepine. It is revealed that a conformational constrain (as a fused ring) is important and that compounds with a six-membered B-ring (as a 1,2,3,4-tetrahydroisoquinoline) in general are more potent than the corresponding isoindoline, 2,3,4,5-tetrahydro-1H-2-benzazepine and 2,3,4,5-tetrahydro-1H-3-benzazepine derivatives.