Pero, Joseph E.; Rossi, Michael A.; Lehman, Hannah D. G. F.; Kelly, Michael J. III; Mulhearn, James J.; Wolkenberg, Scott E.; Cato, Matthew J.; Clements, Michelle K.; Daley, Christopher J.; Filzen, Tracey; Finger, Eleftheria N.; Gregan, Yun; Henze, Darrell A.; Jovanovska, Aneta; Klein, Rebecca; Kraus, Richard L.; Li, Yuxing; Liang, Annie; Majercak, John M.; Panigel, Jacqueline; Urban, Mark O.; Wang, Jixin; Wang, Ying-Hong; Houghton, Andrea K.; Layton, Mark E. published the artcile< Benzoxazolinone aryl sulfonamides as potent, selective Nav1.7 inhibitors with in vivo efficacy in a preclinical pain model>, Application In Synthesis of 112-63-0, the main research area is benzoxazolinone aryl sulfonamide preparation sodium channel inhibitor oral analgesic; Chronic pain; Na(v)1.7 inhibition; Oral bioavailability; Pharmacological selectivity; Voltage-gated sodium channel.
Studies on human genetics have suggested that inhibitors of the Nav1.7 voltage-gated sodium channel hold considerable promise as therapies for the treatment of chronic pain syndromes. Herein, we report novel, peripherally-restricted benzoxazolinone aryl sulfonamides as potent Nav1.7 inhibitors with excellent selectivity against the Nav1.5 isoform, which is expressed in the heart muscle. Elaboration of initial lead compound 3d afforded exemplar 13, which featured attractive physicochem. properties, outstanding lipophilic ligand efficiency and pharmacol. selectivity against Nav1.5 exceeding 1000-fold. Key structure-activity relationships associated with oral bioavailability were leveraged to discover compound 17, which exhibited a comparable potency/selectivity profile as well as full efficacy following oral administration in a preclin. model indicative of antinociceptive behavior.
Bioorganic & Medicinal Chemistry Letters published new progress about Analgesics. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Application In Synthesis of 112-63-0.
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