Novel tetrahydro-beta-carboline-1-carboxylic acids as inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK-2)

Bioorg Med Chem Lett. 2007 Aug 15;17(16):4657-63. doi: 10.1016/j.bmcl.2007.05.070. Epub 2007 May 25.


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.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Carbolines / chemistry*
  • Carbolines / pharmacology*
  • Humans
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • Molecular Structure
  • Rats
  • Structure-Activity Relationship
  • U937 Cells


  • Anti-Inflammatory Agents, Non-Steroidal
  • Carbolines
  • Mitogen-Activated Protein Kinases