Schlotter Karin, Boeckler Frank, Hübner Harald, Gmeiner Peter
Department of Medicinal Chemistry, Emil Fischer Center, Friedrich Alexander University, Schuhstrasse 19, D-91052 Erlangen, Germany.
J Med Chem. 2005 Jun 2;48(11):3696-9. doi: 10.1021/jm050170s.
Metallocene-derived bioisosteres lead to exceptionally strong binding G-protein-coupled receptor ligands, indicating substantial plasticity of the receptor excluded volume. Novel binding profiles of ferrocenylcarboxamides combining subnanomolar Ki values for the dopamine D4 receptor (1a, 0.52 nM; 1b, 0.63 nM) with superpotent serotonin 5-hydroxytryptamine1A (1a, 0.50 nM) and dopamine D3 receptor binding (1b, 0.64 nM) and selective D4 agonist properties of the ruthenocene 1c may be a starting point for highly beneficial central nervous system active drugs.
茂金属衍生的生物电子等排体可产生与G蛋白偶联受体结合力极强的配体，这表明受体排除体积具有很大的可塑性。二茂铁基甲酰胺的新型结合谱显示，其对多巴胺D4受体的结合亲和力达亚纳摩尔级（1a，0.52 nM；1b，0.63 nM），对5-羟色胺1A受体具有超强结合力（1a，0.50 nM），对多巴胺D3受体也有结合作用（1b，0.64 nM），而钌茂化合物1c具有选择性D4激动剂特性，这可能是开发高效中枢神经系统活性药物的起点。
