Johann Wolfgang Goethe University, Institute of Pharmaceutical Chemistry, ZAFES/LiFF/CMP, Max-von-Laue-Str. 9, 60438 Frankfurt/Main, Germany.
Bioorg Med Chem Lett. 2010 Mar 1;20(5):1581-4. doi: 10.1016/j.bmcl.2010.01.089. Epub 2010 Jan 21.
Antagonists of the human histamine H(3) receptor (hH(3)R) often contain a second basic moiety, which is well known to boost affinity on this histamine receptor subtype. Here, we prepared compounds with acidic moieties of different pK(a) values to figure out that the hH(3)R tolerates these functionalities when added to a common pharmacophore blueprint. Depending on the acidic, electronic and steric features the designed ligands showed hH(3)R affinities in the nanomolar concentration range. Additionally, selected ligands were tested but failed as dual acting hH(3)R/hPPAR (human peroxisome proliferator-activated receptor) ligands.
人源组胺 H（3）受体（hH（3）R）拮抗剂通常含有第二个碱性部分，这一点众所周知，可增强该组胺受体亚型的亲和力。在这里，我们制备了具有不同 pKa 值的酸性部分的化合物，以了解当添加到常见的药效团模板时，hH（3）R 可耐受这些功能。根据酸性、电子和空间特征，设计的配体在纳摩尔浓度范围内表现出对 hH（3）R 的亲和力。此外，还测试了选定的配体，但它们未能作为双重作用的 hH（3）R/hPPAR（人过氧化物酶体增殖物激活受体）配体。
