Document Report Card

ID: ALA1122643

Journal: J Med Chem

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

Authors: Chapleo CB, Myers PL, Butler RC, Davis JA, Doxey JC, Higgins SD, Myers M, Roach AG, Smith CF, Stillings MR.

Abstract: Modification of the 1,4-benzodioxan ring present in RX 781094 has not previously been considered. This paper describes a number of analogues of this ring system, including compounds in which one of the oxygen atoms has been replaced by a methylene group and also those in which the ring size has been changed to give, for example, furan and thiophene derivatives. The dihydrobenzofuranylimidazoline compound 7 is the only analogue possessing presynaptic antagonist potency potency and selectivity comparable to that of 1. In view of this result, a number of derivatives was prepared to determine the structure-activity relationships within this series. Many derivatives, as well as the parent compound 7, were found to possess presynaptic alpha 2-adrenoreceptor antagonist and postsynaptic alpha 1-adrenoreceptor partial agonist properties. Two of the selective presynaptic antagonists, 13 and 14 possess greater potency and selectivity than that possessed by 1. The 5-chloro derivative 25 is twice as potent as after oral administration but only about half as potent when given intravenously.

CiteXplore: 6143826

DOI: 10.1021/jm00371a003