Conversion of a Highly Selective Sigma-1 Receptor–Ligand to Sigma-2 Receptor Preferring Ligands with Anticocaine Activity
摘要:
Cocaine's toxicity can be mitigated by blocking its interaction with sigma-1 receptors. The involvement of sigma-2 receptors remains unclear. To investigate their potential role, we have designed compounds through a convergent synthesis utilizing a highly selective sigma-1 ligand and elements of a selective sigma-2 ligand. Among the synthesized compounds was produced a subnanomolar sigma-2 ligand with an 11-fold preference over sigma-1 receptors. These compounds may be useful in developing effective pharmacotherapies for cocaine toxicity.
Conversion of a Highly Selective Sigma-1 Receptor–Ligand to Sigma-2 Receptor Preferring Ligands with Anticocaine Activity
摘要:
Cocaine's toxicity can be mitigated by blocking its interaction with sigma-1 receptors. The involvement of sigma-2 receptors remains unclear. To investigate their potential role, we have designed compounds through a convergent synthesis utilizing a highly selective sigma-1 ligand and elements of a selective sigma-2 ligand. Among the synthesized compounds was produced a subnanomolar sigma-2 ligand with an 11-fold preference over sigma-1 receptors. These compounds may be useful in developing effective pharmacotherapies for cocaine toxicity.
Conversion of a Highly Selective Sigma-1 Receptor–Ligand to Sigma-2 Receptor Preferring Ligands with Anticocaine Activity
作者:Christophe Mésangeau、Sanju Narayanan、Andrea M. Green、Jamaluddin Shaikh、Nidhi Kaushal、Eddy Viard、Yan-Tong Xu、James A. Fishback、Jacques H. Poupaert、Rae R. Matsumoto、Christopher R. McCurdy
DOI:10.1021/jm701357m
日期:2008.3.13
Cocaine's toxicity can be mitigated by blocking its interaction with sigma-1 receptors. The involvement of sigma-2 receptors remains unclear. To investigate their potential role, we have designed compounds through a convergent synthesis utilizing a highly selective sigma-1 ligand and elements of a selective sigma-2 ligand. Among the synthesized compounds was produced a subnanomolar sigma-2 ligand with an 11-fold preference over sigma-1 receptors. These compounds may be useful in developing effective pharmacotherapies for cocaine toxicity.