五环6a,7 - 二氢二吲哚和2,3 - 二氢二吲哚衍生物作为新型褪黑素能配体的合成及药理评价
Synthesis and pharmacological evaluation of pentacyclic 6a,7-dihydrodiindole and 2,3-dihydrodiindole derivatives as novel melatoninergic ligands.
作者信息
Attia Mohamed I, Witt-Enderby Paula A, Julius Justin
机构信息
Pharmaceutical Institute, Pharmaceutical Chemistry Division, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.
出版信息
Bioorg Med Chem. 2008 Aug 15;16(16):7654-61. doi: 10.1016/j.bmc.2008.07.012. Epub 2008 Jul 10.
The synthesis of novel melatonin analogues 3a and 4a-c designed as melatonin receptor ligands is described. Among the newly synthesized ligands, 2-((S)-2-hydroxymethylindolin-1-ylmethyl)-melatonin 4b displayed the highest affinity for MT(1) receptors (K(i)=9.8 nM) and for MT(2) subtype (K(i)=7.8 nM), whereas the rigid pentacyclic ligand 3 showed the highest selectivity towards the MT(2) receptor subtype (K(i)=319.3 nM for MT(1) and K(i)=65.2 nM for MT(2)).
本文描述了设计为褪黑素受体配体的新型褪黑素类似物3a和4a-c的合成。在新合成的配体中，2-((S)-2-羟甲基吲哚啉-1-基甲基)-褪黑素4b对MT(1)受体表现出最高亲和力（K(i)=9.8 nM），对MT(2)亚型也有最高亲和力（K(i)=7.8 nM），而刚性五环配体3对MT(2)受体亚型表现出最高选择性（对MT(1)的K(i)=319.3 nM，对MT(2)的K(i)=65.2 nM）。
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