1417626-86-8Relevant articles and documents
2-Aminopyridine Derivatives as Potential σ2 Receptor Antagonists
Abate, Carmen,Ferorelli, Savina,Niso, Mauro,Lovicario, Cesarea,Infantino, Vittoria,Convertini, Paolo,Perrone, Roberto,Berardi, Francesco
, p. 1847 - 1857 (2012/10/30)
σ2 Receptor research is receiving increasing interest with regard to the potential of σ2 proteins as targets for tumor therapy and diagnosis. Nevertheless, knowledge about the σ2 receptor is far from conclusive. The paucity and modest affinity of known σ2 antagonists represent one of the limitations to σ2 receptor research. Previous studies of the high-affinity σ2 agonist 1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)-n-propyl]piperazine 4 (PB28) suggested that a decrease in lipophilicity might lead to σ2 ligands devoid of antiproliferative activity (potential σ2 antagonists). With the aim of producing σ2 receptor antagonists, we replaced the tetralin nucleus of compound 4 with a 2-aminopyridine moiety. A series of compounds with high affinity for both σ subtypes and with no antiproliferative activity in various cells (mouse HT-22, human SK-N-SH, MCF-7wt, and MCF-7σ1) were obtained. The effect on Ca2+ mobilization was investigated for high-affinity compounds 18 and 4, which showed opposite effects. All of the data support the new 2-aminopyridines as high-affinity σ ligands with σ2 antagonist and σ1 agonist activity, and, despite the lack of significant σ2 versus σ1 selectivity, these novel compounds may be better tools for σ receptor research than the known low-affinity σ2 antagonists.
