Maslowska-Lipowicz Iwona, Figlus Marek, Zuiderveld Obbe P, Walczynski Krzysztof
Department of Synthesis and Technology of Drugs, Medical University, Lódz, Poland.
Arch Pharm (Weinheim). 2008 Dec;341(12):762-73. doi: 10.1002/ardp.200800070.
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 H(3 )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 (hH(3)R, pK(i) = 7.09), 9b1 (hH(3)R, pK(i) = 6.78), 9b5 (hH(3)R, pK(i) = 6.99), and 9b6 (hH(3)R, pK(i )= 6.97) were also tested in vitro as H(3 )receptor antagonists - the electrically evoked contraction of the guinea-pig jejunum. The histaminergic H(1) antagonism of selected compounds 9b1, 9b2, and 9b4-9b6 was established on the isolated guinea-pig ileum by conventional methods; the pA(2) values were compared with the potency of pyrilamine. The compounds did not show any H(1) antagonistic activity (pA(2) < 4; for pyrilamine pA(2) = 9.53).
已制备了一系列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。对所得到的1-苄基-4-羟基哌啶衍生物在稳定表达于HEK 293T细胞中的重组人组胺H(3)受体上的亲和力进行了评估。所有研究的化合物均显示出中度至显著的体外亲和力。该系列中最有效的拮抗剂9b2（hH(3)R，pK(i)=7.09）、9b1（hH(3)R，pK(i)=6.78）、9b5（hH(3)R，pK(i)=6.99）和9b6（hH(3)R，pK(i)=6.97）也作为H(3)受体拮抗剂在体外进行了测试——豚鼠空肠的电诱发收缩。通过常规方法在分离的豚鼠回肠上确定了所选化合物9b1、9b2和9b4 - 9b6的组胺能H(1)拮抗作用；将pA(2)值与吡苄明的效力进行了比较。这些化合物未显示出任何H(1)拮抗活性（pA(2)<4；吡苄明的pA(2)=9.53）。
