Molecular properties of the adrenergic alpha-receptor6. - Optimum carbon chain-length between the inner nitrogenand the sulfur of tetramine disulfides

"The recently reportod tetramine disu fides class of irreversible antagonists show a remarkable topographical dualism towards thealpha-receptor. Two series of alpha-antagonists were developed : the first carries benzyl-type substituents as in 24 or 26 and incorporates a six-carbon chain; the other incorporates an eight- or seven carbon chain but carries no substituent as in 22 or 21. However, onestructural feature was kept constant : the two-carbon chain between a sulfur and an inner nitrogen. In order to evaluate the possibleimportance of that reourring cystamine segment, compounds 5-18 (homologues of 22, 24 arrd 26) were synthesized and tested. Theywere all devoid of activity, thus suggesting that the cystamine moiety constitutes an important structural element for cr-blocking activityin the tetramine disulfides series of alha.blockers. The underlying drug-receptor interaction mechanisms are discussed.