WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 555652
Description: XPC-6444 is a highly potent inhibitors of NaV1.6 with high selectivity over NaV1.1 and NaV1.5. XPC-6444 provided excellent anticonvulsant activity and reduced seizure activity in a dose-dependent manner in an induced seizure model, which utilized SCN8A GOF mice carrying the N1768D mutation identified in a human EIEE13 patient.
MedKoo Cat#: 555652
Chemical Formula: C22H25F3N4O2S2
Exact Mass: 498.1371
Molecular Weight: 498.5832
Elemental Analysis: C, 53.00; H, 5.05; F, 11.43; N, 11.24; O, 6.42; S, 12.86
Synonym: XPC-6444; XPC 6444; XPC6444;
IUPAC/Chemical Name: 4-((2-((tert-Butyl(methyl)amino)methyl)-6-fluorobenzyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide
InChi Key: VOJFVKGTRNXOTJ-UHFFFAOYSA-N
InChi Code: InChI=1S/C22H25F3N4O2S2/c1-22(2,3)29(4)11-14-6-5-7-17(23)16(14)10-26-15-8-18(24)21(19(25)9-15)33(30,31)28-20-12-32-13-27-20/h5-9,12-13,26,28H,10-11H2,1-4H3
SMILES Code: O=S(C1=C(F)C=C(NCC2=C(F)C=CC=C2CN(C(C)(C)C)C)C=C1F)(NC3=CSC=N3)=O
Nonselective antagonists of voltage-gated sodium (NaV) channels have been long used for the treatment of epilepsies. The efficacy of these drugs is thought to be due to the block of sodium channels on excitatory neurons, primarily NaV1.6 and NaV1.2. However, these currently marketed drugs require high drug exposure and suffer from narrow therapeutic indices. Selective inhibition of NaV1.6, while sparing NaV1.1, is anticipated to provide a more effective and better tolerated treatment for epilepsies. In addition, block of NaV1.2 may complement the anticonvulsant activity of NaV1.6 inhibition.
Identification of CNS-Penetrant Aryl Sulfonamides as Isoform-Selective NaV1.6 Inhibitors with Efficacy in Mouse Models of Epilepsy
Thilo Focken*Kristen BurfordMichael E. GrimwoodAlla ZenovaJean-Christophe AndrezWei GongMichael WilsonMatt TaronShannon DeckerVerner LofstrandSultan ChowdhuryNoah ShuartSophia LinSamuel J. GoodchildClint YoungMaegan SorianoParisa K. TariMatthew WaldbrookKaren NelkenbrecherRainbow KwanAndrea LindgrenGina de BoerStephanie LeeLuis SojoRobert J. DeVitaCharles J. CohenSteven S. WesolowskiJ. P. Johnson Jr.Christoph M. DehnhardtJames R. Empfield
Journal of Medicinal Chemistry, Articles ASAP (As Soon As Publishable)Subscribed Access
Publication Date (Web):September 17, 2019