Synthesis and calcium modulatory activity of 3-alkyloxy-carbonyl-4-(disubstituted)aryl-5-oxo-1,4,5,6,7,8-hexa-hydroquinoline derivatives.
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.
Simşek
Rahime
R
Department of Pharmaceutical Chemistry, Hacettepe University, Ankara, Turkey. rsimsek@hacettepe.edu.tr
Oztürk
Gökçe S
GS
Vural
I Mert
IM
Gündüz
Miyase G
MG
Sarioglu
Yusuf
Y
Safak
Cihat
C
D000818:Animals; D002121:Calcium Channel Blockers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002855:Chromatography, Thin Layer; D004305:Dose-Response Relationship, Drug; D005748:Gastric Fundus / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011817:Rabbits; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared; D013329:Structure-Activity Relationship
D002121:Calcium Channel Blockers; D011804:Quinolines; C527674:methyl-2,7,7-trimethyl-4-(2-nitro-5-chlorophenyl)-5-oxo-l,4,5,6,7,8-hexahydroquinoline-3-carboxylate