Unique spirocyclopiperazinium salt. Part 2: synthesis and structure-activity relationship of dispirocyclopiperazinium salts as analgesics

Bioorg Med Chem Lett. 2003 May 19;13(10):1729-32. doi: 10.1016/s0960-894x(03)00213-0.

Abstract

Three series of spirocyclopiperazinium derivatives 5a-d, 6a-f and 17a-d were synthesized and evaluated for their in vivo analgesic activities. Compounds 5a, 17a and 17b exhibited excellent analgesic activity. Two important structure-activity relationships were observed from this study: (1) the quaternary ammonium functionality is a critical pharmacophore for analgesic activity; (2) it is important to adjust the lipophilic property of compounds to improve analgesic activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / administration & dosage
  • Analgesics / chemical synthesis*
  • Analgesics / pharmacology
  • Animals
  • Dose-Response Relationship, Drug
  • Hydrophobic and Hydrophilic Interactions
  • Hypnotics and Sedatives / chemical synthesis
  • Hypnotics and Sedatives / pharmacology
  • Maximum Tolerated Dose
  • Mice
  • Piperazines / administration & dosage
  • Piperazines / chemical synthesis*
  • Piperazines / pharmacology*
  • Salts
  • Spiro Compounds
  • Structure-Activity Relationship

Substances

  • Analgesics
  • Hypnotics and Sedatives
  • Piperazines
  • Salts
  • Spiro Compounds