Novel tetrahydropyrido[3,2-c]pyrroles as 5-HT(7) antagonists

Bioorg Med Chem Lett. 2011 Jan 1;21(1):42-4. doi: 10.1016/j.bmcl.2010.11.078. Epub 2010 Nov 24.

Abstract

The synthesis and SAR for a novel series of tetrahydropyrido[3,2-c]pyrroles is described. Optimization of the pendant aryl ring lead to high binding affinity at the 5-HT(7) receptor when small lipophilic groups were placed in the para position. Modification of the N-benzyl group and secondary amine were not well tolerated. A representative set of compounds was shown to be functional antagonists of the 5-HT(7) receptor.

MeSH terms

  • Animals
  • Protein Binding
  • Pyrroles / chemical synthesis
  • Pyrroles / chemistry*
  • Pyrroles / pharmacokinetics
  • Rats
  • Receptors, Serotonin / chemistry*
  • Receptors, Serotonin / metabolism
  • Serotonin Antagonists / chemical synthesis
  • Serotonin Antagonists / chemistry*
  • Serotonin Antagonists / pharmacokinetics
  • Structure-Activity Relationship

Substances

  • Pyrroles
  • Receptors, Serotonin
  • Serotonin Antagonists
  • serotonin 7 receptor