Studies on the structure-activity relationships of adrenergic .BETA.-mimetic benzylamine derivatives. V. 9-Aryl-1H-2,3,7,8,9,10-hexahydrobenzo[d,e]quinolines.

Publisher Website
Google Scholar
Abstract
The synthesis and .beta.-adrenergic sympathomimetic activities of stereoisomeric 9-aryl-5,6-dihydroxy-1H-2,3,7,8,9,10-hexahydrobenzo[d,e]quinolines, which are constrained analogs of the benzylamine (2), the tetrahydronaphthalenes (3) and trimetoquinol (TMQ), are presented. Structure-activity relationships of these compounds were explained in terms of various spatial orientations of the functional groups in these molecules suggested by inspection of Dreiding model. The conformations of 3b-trans and 5b-trans, both of which are potent tracheal relaxants, are the type A orientation of the functional groups where the catechol and trimethoxyphenyl groups are approximately anti to each other. 5b-Cis which cannot hold the type A orientation was only 1/130 as active as 5b-trans. The spatial orientation of the functional groups in TMQ in the crystalline state was type A. The conformation of TMQ required for manifesting its .beta.2-stimulating activity in vivo is probably similar to that in crystalline state. Contrary to the previous finding that 2 and 3b-trans were active in both .beta.2 and .beta.1 adrenoceptors, 5b-trans possessed high selectivity for .beta.2-adrenoceptors.