32597-35-6Relevant articles and documents
Refinement of the benzodiazepine receptor site topology by structure-activity relationships of new N-(heteroarylmethyl)indol-3- ylglyoxylamides
Primofiore, Giampaolo,Da Settimo, Federico,Marini, Anna Maria,Taliani, Sabrina,La Motta, Concettina,Simorini, Francesca,Novellino, Ettore,Greco, Giovanni,Cosimelli, Barbara,Ehlardo, Marina,Sala, Annalisa,Besnard, Fran?ois,Montali, Marina,Martini, Claudia
, p. 2489 - 2495 (2006)
N-(Heteroarylmethyl)indol-3-ylglyoxylamides (1-26) were synthesized and evaluated as ligands of the benzodiazepine receptor (BzR) to probe the hydrogen bonding properties of the so-called S1 site of the BzR by means of suitable heterocyclic side chains. SARs were developed in light of our hypothesis of binding modes A and B. Pyrrole and furan derivatives adopting mode A (2, 8, 10, 20, 22) turned out to be more potent (Ki values 1 site of the BzR. Compounds 1, 2, 8, 19, 20, and 22, tested at recombinant rat α1β2γ2. α 2β2γ2, and α5β 3γ2 BzRs, elicited selectivity for the α1β2γ2 isoform. On the basis of published mutagenesis studies and the present SARs, we speculate that the S1 HBA/D group might be identified as the hydroxyl of α1-Tyr209 or of other neighboring amino acids.
