Caroon J M, Clark R D, Kluge A F, Lee C H, Strosberg A M
J Med Chem. 1983 Oct;26(10):1426-33. doi: 10.1021/jm00364a013.
The 2R*,11bS* and 2S*,11bS* diastereoisomers of the spiro[1,3,4,6,7,11b-hexahydro-2H-benzo[a]quinolizine-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 optimal. (2S,3S,11bS)-Spiro-[2-ethyl-9,10-dimethoxy-1,3,4,6,7, 11b-hexahydro-2H-benzo[a]quinolizine-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 alpha-adrenoceptor antagonists.
通过立体选择性方法制备了螺[1,3,4,6,7,11b-六氢-2H-苯并[a]喹嗪-2,5'-恶唑烷-2'-酮]体系的2R*,11bS和2S,11bS非对映异构体。通过对自发性高血压大鼠口服给药来评估这些化合物的抗高血压活性，结果表明2S,11bS*系列活性更强。在该系列中发现，3位和4'位的小烷基取代基增强了抗高血压活性，9位和10位的甲氧基取代是最佳的。(2S,3S,11bS)-螺[2-乙基-9,10-二甲氧基-1,3,4,6,7,11b-六氢-2H-苯并[a]喹嗪-2,5'-恶唑烷-2'-酮][(-)-9e]是该系列中最有效的化合物之一，而其对映体(+)-9e无活性。该系列中的选定化合物显示为α-肾上腺素受体拮抗剂。
