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.
Division of Organic Chemistry, Lund University, PO Box 124, SE-221 00 Lund, Sweden.
Magnus
M
Berglund
María F
MF
Dalence-Guzmán
Staffan
S
Skogvall
Olov
O
Sterner
D001993:Bronchodilator Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002396:Catechols / Q000737:chemistry*; D017606:Chlorine Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D012119:Respiration / Q000187:drug effects; D013329:Structure-Activity Relationship
D001993:Bronchodilator Agents; D002396:Catechols; D017606:Chlorine Compounds; C034221:catechol; C071423:capsazepine; D002211:Capsaicin