.alpha.-Adrenoceptor reagents. 2. Effects of modification of the 1,4-benzodioxan ring system on .alpha.-adrenoreceptor activity

Publisher Website
Google Scholar
Abstract
Modification of the 1,4-benzodioxan ring present in RX 781094 [idazoxan] (1) was not previously considered. A number of analogs of this ring system was described, including compounds in which one of the O atoms was replaced by a methylene group and also those in which the ring size is changed to give, for example, furan and thiophene derivatives. The dihydrobenzofuranylimidazoline compound 7 [2-(2,3-dihydro-2-benzofuranyl)-2-imidazoline hydrochloride] is the only analog possessing presynaptic antagonist potency and selectivity comparable to that of 1. Derivatives were prepared to determine the structure-activity relationships within this series. Many derivatives, as well as the parent compound 7, possessed presynaptic .alpha.2-adrenoreceptor antagonist and postsynaptic .alpha.1-adrenoreceptor [rat and mice] partial agonist properties. Two of the selective presynaptic antagonists possess greater potency and selectivity than that possessed by 1. The 5-chloro derivative is twice as potent as 1 after oral administration but only about half as potent when given i.v.