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.
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.
Hu
Tao
T
Department of Medicinal Chemistry, Merck Research Laboratories, MRLSDB2, 3535 General Atomics Court, San Diego, CA 92121, USA. tao_hu@merck.com
Stearns
Brian A
BA
Campbell
Brian T
BT
Arruda
Jeannie M
JM
Chen
Chixu
C
Aiyar
Jayashree
J
Bezverkov
Robert E
RE
Santini
Angelina
A
Schaffhauser
Hervé
H
Liu
Wensheng
W
Venkatraman
Shankar
S
Munoz
Benito
B
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
D015220:Calcium Channels; D008024:Ligands; D011724:Pyridazines; C062482:pyridazine