N,N-dialkyl-2-phenylindol-3-ylglyoxylamides. A new class of potent and selective ligands at the peripheral benzodiazepine receptor.
We report the synthesis and the affinity data at both the peripheral (PBR) and the central benzodiazepine receptors of a series of N,N-dialkyl-2-phenylindol-3-ylglyoxylamide derivatives III, designed as conformationally constrained analogues of 2-phenylindole-3-acetamides II such as FGIN-1-27. Most of the new compounds showed a high specificity and affinity for PBR, with K(i) in the nanomolar to subnanomolar range. The most potent ligands (4-7, 9, 13-27) stimulated steroid biosynthesis in rat C6 glioma cells with a potency similar to or higher than that of classical ligands. The SARs of this new class of compounds are discussed.
Primofiore
Giampaolo
G
Dipartimento di Scienze Farmaceutiche, Università di Pisa, Via Bonanno 6, 56126 Pisa, Italy.
Da Settimo
Federico
F
Taliani
Sabrina
S
Simorini
Francesca
F
Patrizi
Maria Paola
MP
Novellino
Ettore
E
Greco
Giovanni
G
Abignente
Enrico
E
Costa
Barbara
B
Chelli
Beatrice
B
Martini
Claudia
C
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D045744:Cell Line, Tumor; D006038:Glyoxylates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008024:Ligands; D011869:Radioligand Assay; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship
D006038:Glyoxylates; D007211:Indoles; D008024:Ligands; D011963:Receptors, GABA-A