Parallel solid-phase synthesis and characterization of new sulfonamide and carboxamide proline derivatives as potential CNS agents

Bioorg Med Chem. 2005 Apr 15;13(8):3029-35. doi: 10.1016/j.bmc.2005.01.060.

Abstract

A solid-phase synthesis of the 64-member library of novel sulfonamide and carboxamide proline derivatives, focused on the 5-HT7 receptor antagonist SB-258741, was described. The final compounds were obtained in good yields and high purity upon cleavage from SynPhase Lanterns, functionalized by a BAL linker. The library representatives were screened for 5-HT7, 5-HT1A and D2 receptors to explore the impact of a tertiary amine moiety, the length of an alkylene spacer and the aryl fragment on the receptor affinity. The preliminary biological results provided data for further investigation aimed at a search for 5-HT7 receptor agents, and permitted the identification of several compounds with significant 5-HT1A receptor affinity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemistry*
  • Binding, Competitive / drug effects
  • Central Nervous System Agents / chemical synthesis*
  • Central Nervous System Agents / chemistry
  • Central Nervous System Agents / pharmacology
  • Ligands
  • Molecular Structure
  • Piperidines / pharmacology
  • Proline* / analogs & derivatives
  • Proline* / chemical synthesis
  • Proline* / pharmacology
  • Pyrrolidines / pharmacology
  • Radioligand Assay
  • Receptor, Serotonin, 5-HT1A / drug effects
  • Receptors, Dopamine / drug effects
  • Receptors, Serotonin / drug effects
  • Sulfonamides / chemistry*
  • Tosyl Compounds / pharmacology

Substances

  • Amides
  • Central Nervous System Agents
  • Ligands
  • Piperidines
  • Pyrrolidines
  • Receptors, Dopamine
  • Receptors, Serotonin
  • SB258741
  • Sulfonamides
  • Tosyl Compounds
  • serotonin 7 receptor
  • Receptor, Serotonin, 5-HT1A
  • Proline