title: Synthesis and biological evaluation of 6-aryl-6H-pyrrolo[3,4-d]pyridazine derivatives as high-affinity ligands of the alpha(2)delta subunit of voltage-gated calcium channels.
abstract: A novel class of 2H-pyrrolo[3,4-c]pyridazine ligands of the alpha (2) delta subunit of voltage-gated calcium channels is described. Compound 4a with high affinity toward alpha (2) delta was identified through structure-activity relationship studies of the lead compound. Tritiated ligand [(3)H]-4b was synthesized to demonstrate that this ligand binds to the same site as Gabapentin toward alpha (2) delta subunit of voltage-gated calcium channels.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, MRLSDB2, 3535 General Atomics Court, San Diego, CA 92121, USA. tao_hu@merck.com
authors.forename: Tao
authors.initials: T
authors.lastname: Hu
authors.forename: Brian A
authors.initials: BA
authors.lastname: Stearns
authors.forename: Brian T
authors.initials: BT
authors.lastname: Campbell
authors.forename: Jeannie M
authors.initials: JM
authors.lastname: Arruda
authors.forename: Chixu
authors.initials: C
authors.lastname: Chen
authors.forename: Jayashree
authors.initials: J
authors.lastname: Aiyar
authors.forename: Robert E
authors.initials: RE
authors.lastname: Bezverkov
authors.forename: Angelina
authors.initials: A
authors.lastname: Santini
authors.forename: Hervé
authors.initials: H
authors.lastname: Schaffhauser
authors.forename: Wensheng
authors.initials: W
authors.lastname: Liu
authors.forename: Shankar
authors.initials: S
authors.lastname: Venkatraman
authors.forename: Benito
authors.initials: B
authors.lastname: Munoz
mesh_terms: D015220:Calcium Channels / Q000187:drug effects*; D004353:Drug Evaluation, Preclinical; D015640:Ion Channel Gating; D008024:Ligands; D011724:Pyridazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D015220:Calcium Channels; D008024:Ligands; D011724:Pyridazines; C062482:pyridazine