Geometrically constrained derivatives of indolylglyoxylamides as ligands binding the GABAA/BzR complex.
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.
Dipartimento di Scienze Farmaceutiche, Universita di Pisa, Via Bonanno 6, 56126, Pisa, Italy.
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Sartini
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Morelli
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F
Simorini
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Taliani
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Salerno
A M
AM
Marini
F
F
Da Settimo
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C
La Motta
D000577:Amides / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D058785:GABA-A Receptor Agonists / Q000737:chemistry / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists / Q000737:chemistry / Q000494:pharmacology; D006038:Glyoxylates / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D006993:Hypnotics and Sedatives / Q000737:chemistry* / Q000494:pharmacology; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology; D008024:Ligands; D011485:Protein Binding; D021122:Protein Subunits / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014227:Triazines / Q000737:chemistry / Q000494:pharmacology; D014230:Triazoles / Q000737:chemistry / Q000494:pharmacology
D000577:Amides; D014151:Anti-Anxiety Agents; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D006038:Glyoxylates; D006993:Hypnotics and Sedatives; D007211:Indoles; D008024:Ligands; D021122:Protein Subunits; D011963:Receptors, GABA-A; D014227:Triazines; D014230:Triazoles