Ward T J, White J F, Lattimer N, Rhodes K F, Sharma S, Waterfall J F
Department of Chemistry, Wyeth Research (U.K.), Taplow, Maidenhead, Berkshire, England.
J Med Chem. 1988 Jul;31(7):1421-6. doi: 10.1021/jm00402a029.
A series of 2-sulfonamido-1,3,4,6,7,11b alpha-hexahydro-2H-benzo[a]quinolizines were synthesized and examined for alpha 2- and alpha 1-adrenoceptor antagonist activity on the rat vas deferens and anococcygeus muscle, respectively. A number of compounds in this series were shown to be potent and selective alpha 2-adrenoceptor antagonists. Studies on the resolved enantiomers of compounds 6, 10, and 16 showed that alpha 2-adrenoceptor antagonist activity resided primarily in the 2R,11bS isomers, related to the absolute configuration of the alpha 2-antagonist yohimbine, such that the benzene ring and sulfonamide groups in this series were superimposable on the pyrrole and ester groups of yohimbine.
合成了一系列2-磺酰胺基-1,3,4,6,7,11bα-六氢-2H-苯并[a]喹嗪，并分别在大鼠输精管和肛尾肌上检测其对α2和α1肾上腺素能受体的拮抗活性。该系列中的许多化合物被证明是强效且选择性的α2肾上腺素能受体拮抗剂。对化合物6、10和16的拆分对映体的研究表明，α2肾上腺素能受体拮抗活性主要存在于2R,11bS异构体中，这与α2拮抗剂育亨宾的绝对构型有关，使得该系列中的苯环和磺酰胺基团与育亨宾的吡咯和酯基团重叠。
