Aminoderivatives of cycloalkanespirohydantoins: synthesis and biological activity

Farmaco. 2002 Mar;57(3):189-94. doi: 10.1016/s0014-827x(01)01198-3.

Abstract

3-Aminocycloalkanespiro-5-hydantoins were synthesized and their biological activity was studied. In contrast to hydantoins, these compounds failed to induce either anticonvulsive effects in the central nervous system or inhibitory effects on cholinergic contractions in the enteric nervous system. However, they exerted well pronounced, atropinsensitive, contractile effects on the guinea-pig ileum longitudinal muscle preparations. Structure-activity relationships established allow the assumption that: (i) the reduction of the ring size in the molecule of the spirohydantoins leads to an increase in the potency of the respective analogue to induce contractile effect; (ii) the introduction of -NH2 in position 3 increases the ability of all the compounds studied to exert contractions; (iii) the enlargement of the ring leads to: (1) an increase of the degree of desensitization of the preparations; and (2) a decrease (except 1a) of the potency of the analogues to exert contractile effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemical synthesis*
  • Amines / chemistry
  • Amines / pharmacology*
  • Animals
  • Anticonvulsants / pharmacology
  • Central Nervous System / drug effects
  • Dose-Response Relationship, Drug
  • Electric Stimulation
  • Guinea Pigs
  • Hydantoins / chemical synthesis*
  • Hydantoins / chemistry
  • Hydantoins / pharmacology*
  • Ileum / drug effects
  • Ileum / physiology
  • In Vitro Techniques
  • Magnetic Resonance Spectroscopy
  • Male
  • Mass Spectrometry
  • Mice
  • Muscle Contraction / drug effects
  • Seizures / chemically induced
  • Spectrophotometry, Infrared
  • Structure-Activity Relationship

Substances

  • Amines
  • Anticonvulsants
  • Hydantoins