Synthesis, QSAR and calcium channel antagonist activity of new 1,4-dihydropyridine derivatives containing 1-methyl-4,5-dichloroimidazolyl substituents.
A group of dialkyl and diarylester analogues of nifedipine, in which the ortho-nitrophenyl group at position 4 was replaced by a 1-methyl-4,5-dichloroimidazolyl substituent, were synthesized and evaluated as calcium-channel antagonists using the high K(+)concentration of guinea-pig ileum longitudinal smooth muscle. The structure of all compounds was confirmed by IR,(1)H-NMR, and mass spectra. The calcium-channel antagonist activity of compounds 10a-f demonstrated that compound 10b was the most active and 10f the least active one. With unsymmetrical diesters 12a-k, the most active compound was the ethyl, phenethyl derivative. Structural parameters on the calcium-channel antagonist activity were evaluated by QSAR analysis and a linear correlation was found between the -log IC(50) values of these compounds and their constitutional and topological properties.
Hosseini
Maryam
M
Faculty of Chemistry, Islamic Azad University, North Tehran Branch, Tehran, Iran.
Miri
Ramin
R
Amini
Mohsen
M
Mirkhani
Hossein
H
Hemmateenejad
Bahram
B
Ghodsi
Shahram
S
Alipour
Eskandar
E
Shafiee
Abbas
A
D000818:Animals; D002121:Calcium Channel Blockers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004095:Dihydropyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D008958:Models, Molecular; D015394:Molecular Structure; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D021281:Quantitative Structure-Activity Relationship; D013055:Spectrophotometry, Infrared
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D007093:Imidazoles; C038806:1,4-dihydropyridine