title: Novel tetrahydro-beta-carboline-1-carboxylic acids as inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK-2).
abstract: A structure-activity relationship study was conducted on a series of tetrahydro-beta-carboline-1-carboxylic acid analogs in order to identify the key functionality responsible for activity against the mitogen-activated protein kinase-activated protein kinase 2 enzyme (MK-2). The compounds were further evaluated for their ability to inhibit TNFalpha production in U937 cells and in vivo. These compounds represent a novel structural class of compounds capable of inhibiting MK-2 with remarkable selectivity.
authors.affiliation: Department of Medicinal Chemistry, Pfizer Global Research and Development, Chesterfield, MO 63017, USA. john.i.trujillo@pfizer.com
authors.forename: John I
authors.initials: JI
authors.lastname: Trujillo
authors.forename: Marvin J
authors.initials: MJ
authors.lastname: Meyers
authors.forename: David R
authors.initials: DR
authors.lastname: Anderson
authors.forename: Shridhar
authors.initials: S
authors.lastname: Hegde
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Mahoney
authors.forename: William F
authors.initials: WF
authors.lastname: Vernier
authors.forename: Ingrid P
authors.initials: IP
authors.lastname: Buchler
authors.forename: Kun K
authors.initials: KK
authors.lastname: Wu
authors.forename: Syaulan
authors.initials: S
authors.lastname: Yang
authors.forename: Syaluan
authors.initials: S
authors.lastname: Yang
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Hartmann
authors.forename: David B
authors.initials: DB
authors.lastname: Reitz
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology; D002243:Carbolines / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D051381:Rats; D013329:Structure-Activity Relationship; D020298:U937 Cells
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002243:Carbolines; D020928:Mitogen-Activated Protein Kinases