奇特的生物电子等排体：具有亚纳摩尔结合亲和力和新型选择性特征的茂金属衍生G蛋白偶联受体配体。
Fancy bioisosteres: metallocene-derived G-protein-coupled receptor ligands with subnanomolar binding affinity and novel selectivity profiles.
作者信息
Schlotter Karin, Boeckler Frank, Hübner Harald, Gmeiner Peter
机构信息
Department of Medicinal Chemistry, Emil Fischer Center, Friedrich Alexander University, Schuhstrasse 19, D-91052 Erlangen, Germany.
出版信息
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。
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