Design and synthesis of quinazolinone derivatives as anti-inflammatory agents: pharmacophore modeling and 3D QSAR studies

Med Chem. 2014;10(7):711-23. doi: 10.2174/1573406409666131128142843.

Abstract

A series of 36 novel substituted quinazolinone derivatives were synthesized and evaluated for their antiinflammatory activity by carrageenan induced paw inflammation model. The ability of these compounds to inhibit cyclooxygenase (COX-1 and 2) enzyme has been determined in-vitro; the results indicated that quinazolinone derivatives were selective towards COX-2 rather than COX-1. Among the quinazolinone derivatives tested, compound 32 showed better inhibition against COX-2 when compared with Celecoxib. Pharmacophore modeling and 3D QSAR studies were performed in order to elucidate structural insights for the anti-inflammatory activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Carrageenan
  • Cyclooxygenase 1 / metabolism
  • Cyclooxygenase 2 / metabolism
  • Cyclooxygenase Inhibitors / chemical synthesis
  • Cyclooxygenase Inhibitors / chemistry
  • Cyclooxygenase Inhibitors / pharmacology
  • Drug Design*
  • Edema / chemically induced
  • Edema / drug therapy*
  • Inflammation / chemically induced
  • Inflammation / drug therapy*
  • Models, Molecular
  • Molecular Structure
  • Quantitative Structure-Activity Relationship*
  • Quinazolinones / chemical synthesis
  • Quinazolinones / chemistry
  • Quinazolinones / pharmacology*
  • Rats
  • Sheep

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase Inhibitors
  • Quinazolinones
  • Carrageenan
  • Cyclooxygenase 1
  • Cyclooxygenase 2