3-(omega-Aminoalkyl)-5,5-dialkyl(or spirocycloalkyl-1',5-)hydantoins as new 5-HT1A and 5-HT2A receptor ligands

Arch Pharm (Weinheim). 1996 Jun;329(6):283-90. doi: 10.1002/ardp.19963290604.

Abstract

A series of new 3-(omega-aminoalkyl)-5,5-disubstituted hydantoins, containing 1-phenylpiperazine, 1-(o-methoxyphenyl)piperazine or 1,2,3,4-tetrahydroisoquinoline fragments, were synthesized by standard alkylation procedures and their 5-HT1A and 5-HT2A receptor affinities were determined. It has been shown that the investigated derivatives are recognized by 5-HT1A and 5-HT2A receptors due to the presence of a 1-arylpiperazine fragment however, the terminal hydantoin moiety plays an important role in stabilization of the receptor-ligand complex. It has also been found that the two 1-phenylpiperazine derivatives 32 and 36 are new selective 5-HT2A receptor ligands (Ki = 34 and 37 nM, respectively), whereas the derivative of 1-(o-methoxyphenyl)piperazine (38) is a new, highly potent 5-HT1A receptor ligand (Ki = 0.51 nM) with a moderate affinity for 5-HT2A receptors (Ki = 213 nM).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemistry
  • Amines / metabolism
  • Antidepressive Agents / chemical synthesis
  • Antidepressive Agents / pharmacology
  • Hydantoins / chemical synthesis*
  • Hydantoins / pharmacology
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Piperidines / chemical synthesis
  • Piperidines / pharmacology
  • Protein Binding
  • Receptors, Serotonin / metabolism*
  • Serotonin Receptor Agonists / chemical synthesis*
  • Serotonin Receptor Agonists / chemistry
  • Serotonin Receptor Agonists / pharmacology
  • Trazodone / analogs & derivatives
  • Trazodone / pharmacology

Substances

  • Amines
  • Antidepressive Agents
  • Hydantoins
  • Piperidines
  • Receptors, Serotonin
  • Serotonin Receptor Agonists
  • etoperidone
  • Trazodone