SAR studies of capsazepinoid bronchodilators. Part 1: The importance of the catechol moiety and aspects of the B-ring structure.
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.
Division of Organic Chemistry, Lund University, PO Box 124, SE-221 00 Lund, Sweden; Centro de Tecnologia Agroindustrial, Facultad de Ciencias y Tecnologia, Universidad Mayor de San Simón, Cochabamba, Bolivia.
María F
MF
Dalence-Guzmán
Magnus
M
Berglund
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*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D012119:Respiration / Q000187:drug effects; D013329:Structure-Activity Relationship
D001993:Bronchodilator Agents; D002396:Catechols; C034221:catechol; C071423:capsazepine; D002211:Capsaicin