Benzodioxan

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paper describes a number of analogues of this ring system, including compounds in which one of the oxygen atoms has been replaced by a methylene group and also those in which the ring size has been changed to give, for example, furan and thiophene derivatives.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.

Abstract: Compounds having the formula ##STR1## and pharmaceutically acceptable salts thereof wherein R represents 6,7-di(lower alkoxy) or 6,7,8-tri(lower alkoxy); m is 1 or 2, X is --CHR 1 -- or --CH 2 CH 2 --; each R 1 and R 0 may be the same or different and is hydrogen or lower alkyl; each of R 2 and R 3 is hydrogen, lower alkoxy, lower alkyl, halogen, lower alkanoyl, lower alkoxycarbonyl, --CONR 4 R 5 or --SO 2 NR 4 R 5 wherein each of R 4 and R 5 is hydrogen or lower alkyl; processes for their preparation; and their use as regulators of the cardiovascular system, and particularly in the treatment of hypertension.

Abstract: WB4101 (1)-related compounds 5−10 were synthesized, and their biological profile at α1-adrenoreceptor (AR) subtypes and 5-HT1A serotoninergic receptors was assessed by binding assays in Chinese ham...