Synthesis and calcium channel antagonist activity of nifedipine analogues with methylthioimidazole substituent.
Various diester analogues of nifedipine, in which the orthonitrophenyl group at position 4 is replaced by 1-methyl-2-methylthio-5-imidazolyl substituent, were synthesized and evaluated as calcium channel antagonists on guinea-pig ileal smooth muscle. Nifedipine was used as standard. Comparison of the activities of symmetrical esters (3a-e) indicate that increasing the length of alkyl chain in C3 and C5 ester substituents increases the antagonist activity and the n-propyl ester being preferred (IC50= 2.66 x 10(-9) M). In asymmetrical series (6a-g), compound 6g having ethyl and n-butyl ester at C3 and C5 positions of basic dihydropyridine structure was found to be the most active (IC50= 1.32 x 10(-9) M).
Foroumadi
A
A
Kerman University of Medical Sciences, Research Center, Iran. aforoumadi@yahoo.com
Analuie
N
N
Rezvanipour
M
M
Sepehri
G
G
Najafipour
H
H
Sepehri
H
H
Javanmardi
K
K
Esmaeeli
F
F
D000818:Animals; D002121:Calcium Channel Blockers / Q000138:chemical synthesis* / Q000494:pharmacology*; D004095:Dihydropyridines / Q000138:chemical synthesis / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011189:Potassium Chloride / Q000737:chemistry / Q000378:metabolism; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D007093:Imidazoles; D011189:Potassium Chloride; D009543:Nifedipine