A series of 1‐benzyl‐4‐(3‐aminopropyloxy)piperidine and 1‐benzyl‐4‐(5‐aminopentyloxy)piperidine derivatives has been prepared. The 1‐benzyl‐4‐hydroxypiperidine derivatives obtained were evaluated for their affinities at recombinant human histamine H3 receptor, stably expressed in HEK 293T cells. All compounds investigated show moderate to pronounced in‐vitro affinities. The most potent antagonists in this series 9b2 (hH3R, pKi = 7.09), 9b1 (hH3R, pKi = 6.78), 9b5 (hH3R, pKi = 6.99), and 9b6 (hH3R, pKi = 6.97) were also tested in vitro as H3 receptor antagonists – the electrically evoked contraction of the guinea‐pig jejunum. The histaminergic H1 antagonism of selected compounds 9b1, 9b2, and 9b4–9b6 was established on the isolated guinea‐pig ileum by conventional methods; the pA2 values were compared with the potency of pyrilamine. The compounds did not show any H1 antagonistic activity (pA2 < 4; for pyrilamine pA2 = 9.53).

中文翻译：

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作为非咪唑组胺 H3 受体拮抗剂的新型 1-苄基-4-羟基哌啶衍生物

已经制备了一系列 1-苄基-4-(3-氨基丙氧基)哌啶和 1-苄基-4-(5-氨基戊氧基)哌啶衍生物。评估了获得的 1-苄基-4-羟基哌啶衍生物对重组人组胺 H3 受体的亲和力，在 HEK 293T 细胞中稳定表达。研究的所有化合物都显示出中等至显着的体外亲和力。该系列中最有效的拮抗剂 9b2 (hH3R, pKi = 7.09)、9b1 (hH3R, pKi = 6.78)、9b5 (hH3R, pKi = 6.99) 和 9b6 (hH3R, pKi = 6.97) 也作为 H3 进行了体外测试受体拮抗剂——豚鼠空肠的电诱发收缩。通过常规方法在离体的豚鼠回肠上建立了所选化合物 9b1、9b2 和 9b4-9b6 的组胺能 H1 拮抗作用；将 pA2 值与吡拉敏的效力进行比较。