A series of new 1, 4-benzoxazine derivatives (XI, XII) possessing (4-phenyl-1-piperazinyl)alkyl moieties at the 2-position and related compounds (XIII) were synthesized and tested for calcium antagonistic, calmodulin antagonistic and antihypertensive activities. Various compounds had in vitro calmodulin antagonistic activity superior or comparable to that of trifluoperazine. Among these compounds, tetrahydronaphtho[2, 3-b][1, 4]oxazine derivatives such as 51, 53, 54, 58, 59, 60, 73 and 75 showed potent antihypertensive effects in spontaneously hypertensive rats. Optical isomers of 51 were also synthesized and evaluated biologically. No differences in biological activities were seen between the enantiomers.
一系列新的1,4-苯并恶嗪衍
生物(XI,XII)在2位具有(4-苯基-1-
哌嗪基)烷基部分及相关化合物(XIII)被合成并测试了
钙拮抗、
钙调素拮抗和降压活性。多种化合物在体外表现出优于或相当于
三氟拉嗪的
钙调素拮抗活性。其中,四氢
萘并[2,3-b][1,4]恶嗪衍
生物如51、53、54、58、59、60、73和75在自发性高血压大鼠中显示出强大的降压效果。51的光学异构体也被合成并进行了
生物学评估。这些光学异构体之间在
生物活性上没有差异。