Synthesis and Antihypertensive Activity of a Series of Spiroquinolizine-2,5'-oxazolidin-2'-one>s

Article abstract of DOI:10.1021/jm00364a013

The 2R^*,11bS^* and 2S^*,11bS^* diastereoisomers of the spiro<1,3,4,6,7,11b-hexahydro-2H-benzoquinolizine-2,5'-oxazolidin-2'-one> system were prepared by stereoselective methods.Evaluation of these compounds for antihypertensive activity by oral administration to the spontaneously hypertensive rat showed the 2S^*,11bS^* series was the more potent.Within that series it was found that small alkyl substituents at positions 3 and 4' enhanced antihypertensive activity and that methoxyl substitution at positions 9 and 10 was optical. (2S,3S,11bS)-Spiro<2-ethyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-benzoquinolizine-2,5'-oxazolidin-2'-one> <(-)-9e> was one of the most efficacious compounds of this series, while its antipode, (+)-9e, was inactive.Selected compounds in this series were shown to be α-adrenoceptor antagonists.