Synthesis of conformationally constrained analogues of KN62, a potent antagonist of the P2X7-receptor

Bioorg Med Chem Lett. 2000 Apr 3;10(7):681-4. doi: 10.1016/s0960-894x(00)00083-4.


Conformationally constrained analogues of KN62 containing 1,2,3,4-tetrahydro-7-hydroxyisoquinoline-3-carboxylic acid with S configuration in position 3 were synthesized and their antagonist activities were tested on human macrophage cells. While KN62 is a potent antagonist of the P2X7 receptor, these analogues were inactive as antagonists and only one compound showed appreciable activity as P2X7 antagonist, which was 30 times weaker than that reported for KN62.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / analogs & derivatives*
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / chemical synthesis
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / chemistry
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology
  • Calcium / metabolism
  • Humans
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Purinergic P2 Receptor Antagonists*
  • Receptors, Purinergic P2X7
  • Structure-Activity Relationship


  • P2RX7 protein, human
  • Purinergic P2 Receptor Antagonists
  • Receptors, Purinergic P2X7
  • KN 62
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Calcium