Bregman, Howard; Simard, Jeffrey R.; Andrews, Kristin L.; Ayube, Shawn; Chen, Hao; Gunaydin, Hakan; Guzman-Perez, Angel; Hu, Jiali; Huang, Liyue; Huang, Xin; Krolikowski, Paul H.; Lehto, Sonya G.; Lewis, Richard T.; Michelsen, Klaus; Pegman, Pamela; Plant, Matthew H.; Shaffer, Paul L.; Teffera, Yohannes; Yi, Shuyan; Zhang, Maosheng; Gingras, Jacinthe; DiMauro, Erin F. published the artcile< The Discovery and Hit-to-Lead Optimization of Tricyclic Sulfonamides as Potent and Efficacious Potentiators of Glycine Receptors>, HPLC of Formula: 55279-29-3, the main research area is sulfonamide glycine receptor analgesic pain.
Current pain therapeutics suffer from undesirable psychotropic and sedative side-effects, as well as abuse potential. Glycine receptors (GlyRs) are inhibitory ligand-gated ion channels expressed in nerves of the spinal dorsal horn, where their activation is believed to reduce transmission of painful stimuli. Herein, the authors describe the identification and hit-to-lead optimization of a novel class of tricyclic sulfonamides as allosteric GlyR potentiators. Initial optimization of high-throughput screening (HTS) hit led to the identification of a compound, which demonstrated ex vivo potentiation of glycine-activated current in mouse dorsal horn neurons from spinal cord slices. Further improvement of potency and pharmacokinetics produced in vivo proof-of-concept tool mol. I (AM-1488) which reversed tactile allodynia in a mouse spared-nerve injury (SNI) model. Addnl. structural optimization provided highly potent potentiator II (AM-3607), which was cocrystd. with human GlyRα3cryst to afford the first described potentiator-bound x-ray cocrystal structure within this class of ligand-gated ion channels (LGICs).
Journal of Medicinal Chemistry published new progress about Analgesics. 55279-29-3 belongs to class pyridine-derivatives, and the molecular formula is C6H6N2O, HPLC of Formula: 55279-29-3.