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

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=15 nM) and (S)-22 (IC50=30 nM). A potent and selective radioligand, [3H]-(S)-22 was also synthesized to demonstrate that this ligand binds to the same site as gabapentin.