An indolo[3,2‐d]pyrrolo[3,2‐g]azecine and a benzo[d]pyrrolo[3,2‐g]azecine analogue of the potent dopamine receptor antagonist LE 300 (7‐methyl‐6,7,8,9,14,15‐hexahydro‐5H‐benz‐[d]indolo[2,3‐g]azecine) have been prepared in multi‐step reactions via C‐N bond cleavage of corresponding quaternary N‐methylquinolizinium iodides. LE 300, the target compounds and two precursor quinolizines have been tested in vitro for antagonist activity at 5‐HT2A receptors (rat tail artery) and H1 receptors (guinea‐pig ileum), respectively. LE 300 and compound 19 (3,6‐dimethyl‐ 4,5,6,7,8,13‐hexahydro‐3H‐benzo[d]pyrrolo[3,2‐g]azecine) competitively inhibited 5‐HT‐induced contractions with similar nanomolar potency (pA2 = 8.32 and 8.01, respectively) but were less active than the reference antagonist ketanserin (pA2 = 9.55). Compound 19 displayed moderate H1‐antihistaminic activity in the guinea‐pig ileum assay (pA2 = 7.37).

中文翻译：

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与苯并[d]相比，新型杂环吲哚[3,2-d]吡咯并[3,2-g]氮杂和苯并[d]吡咯并[3,2-g]氮杂的衍生物的合成和5-HT2A拮抗活性]吲哚[2,3-g]氮杂环辛衍生物LE 300

多巴胺受体拮抗剂LE 300（7-甲基-6,7）的吲哚并[3,2-d]吡咯并[3,2-g]氮杂和苯并[d]吡咯并[3,2-g]氮杂,8,9,14,15-六氢-5H-苯并-[d]吲哚并[2,3-g]氮杂）通过相应季N-甲基喹啉鎓碘化物的C-N键断裂在多步反应中制备。LE 300、目标化合物和两种前体喹啉已分别在体外测试了对 5-HT2A 受体（大鼠尾动脉）和 H1 受体（豚鼠回肠）的拮抗活性。LE 300 和化合物 19（3,6-二甲基-4,5,6,7,8,13-六氢-3H-苯并[d]吡咯并[3,2-g]azecine）竞争性抑制 5-HT 诱导的收缩具有相似的纳摩尔效力（分别为 pA2 = 8.32 和 8.01），但活性低于参考拮抗剂酮色林（pA2 = 9.55）。