Eichstadt K E, Reepmeyer J C, Cook R B, Riley P G, Davis D P, Wiley R A
J Med Chem. 1976 Jan;19(1):47-51. doi: 10.1021/jm00223a010.
The synthesis of several novel analogs of amitriptyline and chlorprothixene, in a number of which the position of the side-chain nitrogen atom rigidly fixed with respect to the tricyclic nucleus, is described. The compounds were evaluated for antidepressant-like activity in the Dopa and serotonin interaction tests and for potential antipsychotic activity in the methamphetamine interaction test. 5-(3-Dimethylaminocyclohex-1-enyl)-5H-dibenzo[a,d]cycloheptene (12) was about equipotent with imipramine in the Dopa and methamphetamine tests, and 3-chloro-10,11-dihydro-5H-dibenzo[a,d]cycloheptene-5-spiro-6'-3'-methyl-3'-azabicyclo[3.1.0]hexane (23) also displayed marked activity in the same tests. Prototype compounds for other ring systems, 3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene tropane (16) and 5-(3-dimethylaminocycloheptylidene)-10,11-dihydro-5H-dibenzo[a,d]cycloheptene (18), were less active.
本文描述了几种新型阿米替林和氯丙硫蒽类似物的合成，其中一些类似物中侧链氮原子相对于三环核的位置被严格固定。在多巴与血清素相互作用试验中对这些化合物的抗抑郁样活性进行了评估，并在甲基苯丙胺相互作用试验中对其潜在的抗精神病活性进行了评估。5-(3-二甲氨基环己-1-烯基)-5H-二苯并[a,d]环庚烯(12)在多巴和甲基苯丙胺试验中的效力与丙咪嗪相当，3-氯-10,11-二氢-5H-二苯并[a,d]环庚烯-5-螺-6'-3'-甲基-3'-氮杂双环[3.1.0]己烷(23)在相同试验中也显示出显著活性。其他环系的原型化合物，3-(10,11-二氢-5H-二苯并[a,d]环庚烯-5-亚基)托烷(16)和5-(3-二甲氨基环庚亚基)-10,11-二氢-5H-二苯并[a,d]环庚烯(18)，活性较低。
