SAR studies of capsazepinoid bronchodilators. Part 2: Chlorination and catechol replacement in the A-ring

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 paper concerns the chlorination of the A-ring as well as the replacement of the catechol with bioisosteric groups. It is revealed that chlorination of the A-ring has a profound effect on activity. Moreover, di-chlorination of the 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline structure results in a 10-fold increase in potency compared to capsazepine.

The dependence of the bronchodilating activity in human small airways of capsazepine derivatives on the chlorination of the A-ring and the replacement of the catechol moiety with bioisosteric groups has been investigated.Figure optionsDownload as PowerPoint slide