Dipartimento di Scienze Farmaceutiche, Universita di Pisa, Via Bonanno 6, 56126, Pisa, Italy.
Curr Top Med Chem. 2012;12(4):312-20. doi: 10.2174/156802612799078829.
Indolylglyoxylamides are a class of distinctive benzodiazepine receptor ligands, proposed in the mid-eighties as open analogues of -carbolines. Thorough and long-lasting studies of their structure-activity relationships led to the development of a great deal of derivatives, to satisfy increasingly structural and pharmacophoric requirements of the benzodiazepine binding site in the central nervous system. Efforts to pre-organize their flexible structure in the three-dimensional shape adopted when bound to the receptor led to the identification of two novel classes of rigid ligands, characterized by planar tricyclic heteroaromatic cores: the [1,2,4]triazino[4,3-a]benzimidazol-4(10H)-one and the [1,2,3]triazolo[1,2-a][1,2,4]benzotriazin-1,5(6H)-dione. The present review focuses on these selected classes of ligands, whose rational development, in terms of chemical structures and structure-activity relationships, will be fully discussed.
吲哚基乙二酰胺是一类独特的苯二氮䓬受体配体，它们在 80 年代中期被提出作为 - 咔啉的开放类似物。对其结构-活性关系的深入和持久研究导致了大量衍生物的开发，以满足中枢神经系统苯二氮䓬结合部位日益增加的结构和药效团要求。为了预先组织它们在与受体结合时采用的三维形状的柔性结构，人们确定了两类新型刚性配体，其特征是具有平面三环杂芳核：[1,2,4]三嗪并[4,3-a]苯并咪唑-4(10H)-酮和[1,2,3]三唑并[1,2-a][1,2,4]苯并三嗪-1,5(6H)-二酮。本综述重点介绍了这些精选的配体类别，将全面讨论它们在化学结构和结构-活性关系方面的合理发展。
