Identification and synthesis of [1,2,4]triazolo[3,4-a]phthalazine derivatives as high-affinity ligands to the α2δ -1 subunit of voltage gated calcium channel

Article abstract of DOI:10.1016/j.bmcl.2004.03.008

We have identified and synthesized a series of [1,2,4]triazolo[3,4-a] phthalazine derivatives as high-affinity ligands to α₂δ-1 subunit of voltage gated calcium channels. Structure-activity relationship studies directed toward improving the potency and physical properties of 2 lead to the discovery of 20 (IC₅₀=15nM) and (S)-22 (IC₅₀=30nM). A potent and selective radioligand, [³H]-(S)-22 was also synthesized to demonstrate that this ligand binds to the same site as gabapentin.