title: Discovery and Optimization of Selective Nav1.8 Modulator Series That Demonstrate Efficacy in Preclinical Models of Pain.
abstract: Voltage-gated sodium channels, in particular Nav1.8, can be targeted for the treatment of neuropathic and inflammatory pain. Herein, we described the optimization of Nav1.8 modulator series to deliver subtype selective, state, and use-dependent chemical matter that is efficacious in preclinical models of neuropathic and inflammatory pain.
authors.affiliation: Worldwide Medicinal Chemistry, Pfizer Neusentis , The Portway Building, Granta Park, Great Abington, Cambridge CB21 6GS, U.K.
authors.forename: Sharan K
authors.initials: SK
authors.lastname: Bagal
authors.affiliation: Neusentis U.K., Pfizer Global R&D , The Portway Building, Granta Park, Cambridge CB21 6GS, U.K.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Bungay
authors.affiliation: Worldwide Medicinal Chemistry, Pfizer Global R&D , Sandwich CT13 9NJ, U.K.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Denton
authors.affiliation: Worldwide Medicinal Chemistry, Pfizer Global R&D , Sandwich CT13 9NJ, U.K.
authors.forename: Karl R
authors.initials: KR
authors.lastname: Gibson
authors.affiliation: Worldwide Medicinal Chemistry, Pfizer Global R&D , Sandwich CT13 9NJ, U.K.
authors.forename: Melanie S
authors.initials: MS
authors.lastname: Glossop
authors.affiliation: Worldwide Medicinal Chemistry, Pfizer Global R&D , Sandwich CT13 9NJ, U.K.
authors.forename: Tanya L
authors.initials: TL
authors.lastname: Hay
authors.affiliation: Worldwide Medicinal Chemistry, Pfizer Global R&D , Sandwich CT13 9NJ, U.K.
authors.forename: Mark I
authors.initials: MI
authors.lastname: Kemp
authors.affiliation: Worldwide Medicinal Chemistry, Pfizer Global R&D , Sandwich CT13 9NJ, U.K.
authors.forename: Charlotte A L
authors.initials: CA
authors.lastname: Lane
authors.affiliation: Worldwide Medicinal Chemistry, Pfizer Global R&D , Sandwich CT13 9NJ, U.K.
authors.forename: Mark L
authors.initials: ML
authors.lastname: Lewis
authors.affiliation: Worldwide Medicinal Chemistry, Pfizer Global R&D , Sandwich CT13 9NJ, U.K.
authors.forename: Graham N
authors.initials: GN
authors.lastname: Maw
authors.affiliation: Worldwide Medicinal Chemistry, Pfizer Global R&D , Sandwich CT13 9NJ, U.K.
authors.forename: William A
authors.initials: WA
authors.lastname: Million
authors.affiliation: Neusentis U.K., Pfizer Global R&D , The Portway Building, Granta Park, Cambridge CB21 6GS, U.K.
authors.forename: C Elizabeth
authors.initials: CE
authors.lastname: Payne
authors.affiliation: Worldwide Medicinal Chemistry, Pfizer Global R&D , Sandwich CT13 9NJ, U.K.
authors.forename: Cedric
authors.initials: C
authors.lastname: Poinsard
authors.affiliation: Worldwide Medicinal Chemistry, Pfizer Global R&D , Sandwich CT13 9NJ, U.K.
authors.forename: David J
authors.initials: DJ
authors.lastname: Rawson
authors.affiliation: Worldwide Medicinal Chemistry, Pfizer Global R&D , Sandwich CT13 9NJ, U.K.
authors.forename: Blanda L
authors.initials: BL
authors.lastname: Stammen
authors.affiliation: Neusentis U.K., Pfizer Global R&D , The Portway Building, Granta Park, Cambridge CB21 6GS, U.K.
authors.forename: Edward B
authors.initials: EB
authors.lastname: Stevens
authors.affiliation: Worldwide Medicinal Chemistry, Pfizer Global R&D , Sandwich CT13 9NJ, U.K.
authors.forename: Lisa R
authors.initials: LR
authors.lastname: Thompson
keywords: Nav1.8; SCN10A; TTX-R; Voltage-gated sodium channels; sodium channel drugs