Synthesis, potential anti-inflammatory and analgesic activities study of (S)-N-substituted-1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxamides

Bioorg Med Chem Lett. 2017 Aug 1;27(15):3378-3381. doi: 10.1016/j.bmcl.2017.06.002. Epub 2017 Jun 3.

Abstract

A series of (S)-N-substitued-1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxamide derivatives were designed, synthesized and evaluated for their anti-inflammatory and analgesic effects in vivo. Among the synthesized compounds 2a and 2n showed the best anti-inflammatory activity (inhibition rate: 95% and 92.7%, respectively) and analgesic effect (inhibition rate: 100% and 100%, respectively), which was greater than that or nearly equivalent to that of indomethacin. Compounds 2a and 2n were selected to test their inhibitory effects against ovine COX-1 and COX-2 using the cyclooxygenase inhibition assay in vitro. Compounds 2a and 2n are weak inhibitors of COX-1 isozyme but displayed moderate COX-2 isozyme inhibitory effects (IC50=0.47μM and 1.63μM, respectively) and COX-2 selectivity indexes (SI=11.5 and 4.8). Furthermore, compound 2a was more inhibitors of COX-2 isozyme active than the reference drug celecoxib.

Keywords: Analgesic; Anti-inflammatory; COX-1/COX-2; Inhibition assay; Isoquinoline-2(1H)-carboxamides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / chemical synthesis
  • Analgesics / chemistry
  • Analgesics / pharmacology*
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Cyclooxygenase 1 / metabolism
  • Cyclooxygenase 2 / metabolism
  • Cyclooxygenase Inhibitors / chemical synthesis
  • Cyclooxygenase Inhibitors / chemistry
  • Cyclooxygenase Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Edema / chemically induced
  • Edema / drug therapy*
  • Isoquinolines / chemical synthesis
  • Isoquinolines / chemistry
  • Isoquinolines / pharmacology*
  • Mice
  • Molecular Structure
  • Pain / drug therapy*
  • Stereoisomerism
  • Structure-Activity Relationship
  • Xylenes

Substances

  • 1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxamide
  • Analgesics
  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase Inhibitors
  • Isoquinolines
  • Xylenes
  • Cyclooxygenase 1
  • Cyclooxygenase 2