Novel tetrahydro-beta-carboline-1-carboxylic acids as inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK-2).
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.
Trujillo
John I
JI
Department of Medicinal Chemistry, Pfizer Global Research and Development, Chesterfield, MO 63017, USA. john.i.trujillo@pfizer.com
Meyers
Marvin J
MJ
Anderson
David R
DR
Hegde
Shridhar
S
Mahoney
Matthew W
MW
Vernier
William F
WF
Buchler
Ingrid P
IP
Wu
Kun K
KK
Yang
Syaulan
S
Yang
Syaluan
S
Hartmann
Susan J
SJ
Reitz
David B
DB
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
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002243:Carbolines; D020928:Mitogen-Activated Protein Kinases