A novel structural class of potent inhibitors of NF-kappa B activation: structure-activity relationships and biological effects of 6-aminoquinazoline derivatives

Bioorg Med Chem. 2003 Sep 1;11(18):3869-78. doi: 10.1016/s0968-0896(03)00438-3.

Abstract

In this study, we have investigated the roles of substituents on the terminal phenyl ring at the C(4)-position of the quinazoline core to complete the structure-activity relationships (SARs) of our NF-kappa B activation inhibitors. Among them, compound 12j afforded highly potent inhibitory activity toward NF-kappa B transcriptional activation with IC(50) value of 2 nM, along with an excellent in vivo efficacy by reducing the edema formation seen in carrageenin-induced inflammation of the rat hind paw.

Publication types

  • Comparative Study

MeSH terms

  • Aminoquinolines / chemistry*
  • Aminoquinolines / pharmacology
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Carrageenan
  • Edema / chemically induced
  • Edema / drug therapy
  • Inflammation / chemically induced
  • Inhibitory Concentration 50
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • Quinazolines / chemistry*
  • Quinazolines / pharmacology
  • Rats
  • Spleen / cytology
  • Spleen / drug effects
  • Spleen / growth & development
  • Structure-Activity Relationship
  • Transcriptional Activation / drug effects
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • 6-amino-4-(4-n-pentyloxy)phenethylaminoquinazoline
  • Aminoquinolines
  • Anti-Inflammatory Agents, Non-Steroidal
  • NF-kappa B
  • Quinazolines
  • Tumor Necrosis Factor-alpha
  • 6-aminoquinoline
  • Carrageenan