Acidic elements in histamine H(3) receptor antagonists.
Acidic elements in histamine H(3) receptor antagonists.
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组胺 H(3) 受体拮抗剂中的酸性成分。
DOI：
10.1016/j.bmcl.2010.01.089
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发表时间：
2010
影响因子：
2.7
通讯作者：
H. Stark
中科院分区：
文献类型：
--
作者：
K. Sander;Y. von Coburg;J. Camelin;X. Ligneau;O. Rau;M. Schubert;J. Schwartz;H. Stark
人组胺H3受体（hH 3R）的拮抗剂通常含有第二个碱性部分，众所周知其增强对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，以确定当添加到共同的药效团蓝图中时，hH 3R耐受这些功能。根据酸性，电子和空间的功能，所设计的配体显示hH 3R亲和力在纳摩尔浓度范围内。此外，测试了所选择的配体，但作为双作用hH 3R/hPPAR（人过氧化物酶体增殖物激活受体）配体失败。
Antagonists of the human histamine H3receptor (hH3R) 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 pKavalues to figure out that the hH3R tolerates these functionalities when added to a common pharmacophore blueprint. Depending on the acidic, electronic and steric features the designed ligands showed hH3R affinities in the nanomolar concentration range. Additionally, selected ligands were tested but failed as dual acting hH3R/hPPAR (human peroxisome proliferator-activated receptor) ligands.