title: Synthesis and SAR development of novel P2X7 receptor antagonists for the treatment of pain: part 1.
abstract: Structure-activity relationship (SAR) efforts around our initial lead compound 1 led to the identification of potent P2X(7) receptor antagonists with improved pharmacokinetic profiles. These compounds were potent and selective at the P2X(7) receptor in both human and rodent. Compound (entry 31) exhibited oral efficacy in the rat MIA and CCI pain models.
authors.affiliation: Merck Research Laboratories, Kenilworth, NJ 07033-0539, USA. Julius.Matasi@merck.com
authors.forename: Julius J
authors.initials: JJ
authors.lastname: Matasi
authors.forename: Stephanie
authors.initials: S
authors.lastname: Brumfield
authors.forename: Deen
authors.initials: D
authors.lastname: Tulshian
authors.forename: Michael
authors.initials: M
authors.lastname: Czarnecki
authors.forename: William
authors.initials: W
authors.lastname: Greenlee
authors.forename: Charles G
authors.initials: CG
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: Youngliang
authors.initials: Y
authors.lastname: Sun
authors.forename: Rosalia
authors.initials: R
authors.lastname: Bertorelli
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: D000284:Administration, Oral; D000700:Analgesics / Q000138:chemical synthesis* / Q000737:chemistry; D000818:Animals; D004195:Disease Models, Animal; D015195:Drug Design; D006801:Humans; D015394:Molecular Structure; D010146:Pain / Q000188:drug therapy; D058919:Purinergic P2 Receptor Antagonists / Q000138:chemical synthesis* / Q000737:chemistry; D051381:Rats; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000700:Analgesics; D058919:Purinergic P2 Receptor Antagonists; D058486:Receptors, Purinergic P2X7