title: Synthesis and SAR development of novel P2X7 receptor antagonists for the treatment of pain: part 2.
abstract: Novel P2X(7) antagonists were developed using a purine scaffold. These compounds were potent and selective at the P2X(7) receptor in human and rodent as well as efficacious in rodent pain models. Compound 15a was identified to have oral potency in several pain models in rodent similar to naproxen, gabapentin and pregabalin. Structure-activity relationship (SAR) development and results of pain models are presented.
authors.affiliation: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033-0539, USA. Stephanie.Brumfield@merck.com
authors.forename: Stephanie
authors.initials: S
authors.lastname: Brumfield
authors.forename: Julius J
authors.initials: JJ
authors.lastname: Matasi
authors.forename: Deen
authors.initials: D
authors.lastname: Tulshian
authors.forename: Michael
authors.initials: M
authors.lastname: Czarniecki
authors.forename: William
authors.initials: W
authors.lastname: Greenlee
authors.forename: Charles
authors.initials: C
authors.lastname: Garlisi
authors.forename: Hongchen
authors.initials: H
authors.lastname: Qiu
authors.forename: Kristine
authors.initials: K
authors.lastname: Devito
authors.forename: Shu-Cheng
authors.initials: SC
authors.lastname: Chen
authors.forename: Yongliang
authors.initials: Y
authors.lastname: Sun
authors.forename: Rosalia
authors.initials: R
authors.lastname: Bertorelli
authors.forename: Justin
authors.initials: J
authors.lastname: Ansell
authors.forename: William
authors.initials: W
authors.lastname: Geiss
authors.forename: Van-Duc
authors.initials: VD
authors.lastname: Le
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Martin
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Vellekoop
authors.forename: James
authors.initials: J
authors.lastname: Haber
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Allard
mesh_terms: D000818:Animals; D006801:Humans; D010146:Pain / Q000188:drug therapy*; D058920:Purinergic P2X Receptor Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D011687:Purines / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D051381:Rats; D058486:Receptors, Purinergic P2X7 / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D058920:Purinergic P2X Receptor Antagonists; D011687:Purines; D058486:Receptors, Purinergic P2X7