Synthesis and calcium modulatory activity of 3-alkyloxy-carbonyl-4-(disubstituted)aryl-5-oxo-1,4,5,6,7,8-hexa-hydroquinoline derivatives

Arch Pharm (Weinheim). 2008 Jan;341(1):55-60. doi: 10.1002/ardp.200700087.

Abstract

In this study, twelve hexahydroquinoline derivatives which are condensed analogs of the 1,4-DHP molecule were synthesized and evaluated for their calcium-antagonistic activity. The results indicated that all compounds and nifedipine produced concentration-dependent relaxation in rabbit gastric fundus smooth muscle strips. The relaxant effects of the compounds on the tissues were expressed as percentage of the precontraction using Ca(2+). The maximum response (E(max)) and pD(2)values (the negative logarithm of the concentration for the half-maximal response (EC(50))) were calculated. It is generally believed that introduction of a second electron-withdrawing substituent into the phenyl ring increases the mentioned activity. Methyl-2,7,7-trimethyl-4-(2-nitro-5-chlorophenyl)-5-oxo-l,4,5,6,7,8-hexahydroquinoline-3-carboxylate 2a has been found to be the most active compound in this serie.

MeSH terms

  • Animals
  • Calcium Channel Blockers / chemical synthesis*
  • Calcium Channel Blockers / chemistry
  • Calcium Channel Blockers / pharmacology
  • Chromatography, Thin Layer
  • Dose-Response Relationship, Drug
  • Gastric Fundus / drug effects
  • Gastric Fundus / physiology
  • In Vitro Techniques
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Muscle Relaxation / drug effects
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / physiology
  • Quinolines / chemical synthesis*
  • Quinolines / chemistry
  • Quinolines / pharmacology
  • Rabbits
  • Spectrophotometry, Ultraviolet
  • Spectroscopy, Fourier Transform Infrared
  • Structure-Activity Relationship

Substances

  • Calcium Channel Blockers
  • Quinolines
  • methyl-2,7,7-trimethyl-4-(2-nitro-5-chlorophenyl)-5-oxo-l,4,5,6,7,8-hexahydroquinoline-3-carboxylate