title: Synthesis, QSAR and calcium channel antagonist activity of new 1,4-dihydropyridine derivatives containing 1-methyl-4,5-dichloroimidazolyl substituents.
abstract: 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.
authors.affiliation: Faculty of Chemistry, Islamic Azad University, North Tehran Branch, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Hosseini
authors.forename: Ramin
authors.initials: R
authors.lastname: Miri
authors.forename: Mohsen
authors.initials: M
authors.lastname: Amini
authors.forename: Hossein
authors.initials: H
authors.lastname: Mirkhani
authors.forename: Bahram
authors.initials: B
authors.lastname: Hemmateenejad
authors.forename: Shahram
authors.initials: S
authors.lastname: Ghodsi
authors.forename: Eskandar
authors.initials: E
authors.lastname: Alipour
authors.forename: Abbas
authors.initials: A
authors.lastname: Shafiee
mesh_terms: 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
chemical_list: D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D007093:Imidazoles; C038806:1,4-dihydropyridine