Elsinghorst Paul W, Tanarro Camino M Gonzalez, Gütschow Michael
Pharmazeutisches Institut, Rheinische Friedrich-Wilhelms-Universität Bonn, An der Immenburg 4, D-53121 Bonn, Germany.
J Med Chem. 2006 Dec 14;49(25):7540-4. doi: 10.1021/jm060742o.
Two series of novel heterobivalent tacrine derivatives were synthesized. A trimethoxy substituted benzene was linked to the tacrine moiety by a hydrazide-based linker. The compounds were evaluated as cholinesterase inhibitors, and trimethoxybenzoic acid derivatives with 11- or 12-atom spacers were the most potent inhibitors of human acetylcholinesterase. The inhibitors showed a surprising selectivity toward human butyrylcholinesterase, where several trimethoxyphenylpropionic acid derivatives had IC(50) values less than 250 pM.
合成了两类新型的异双价他克林衍生物。通过基于酰肼的连接基将一个三甲氧基取代的苯连接到他克林部分。对这些化合物进行了胆碱酯酶抑制剂评估，具有11或12个原子间隔基的三甲氧基苯甲酸衍生物是最有效的人乙酰胆碱酯酶抑制剂。这些抑制剂对人丁酰胆碱酯酶表现出惊人的选择性，其中几种三甲氧基苯基丙酸衍生物的IC(50)值小于250 pM。
