Design, synthesis, and calcium channel antagonist activity of new 1,4-dihydropyridines containing 4-(5)-chloro-2-ethyl-5-(4)-imidazolyl substituent.
A series of dialkyl, dicycloalkyl, and diaryl ester analogues of nifedipine, in which the ortho-nitro phenyl group at position 4 is replaced by the 4-(5)-chloro-2-ethyl-5-(4)-imidazolyl substituent, were synthesized and evaluated as calcium channel antagonists using the high K+ contraction of guinea pig ileal longitudinal smooth muscle. The results for the symmetrical ester series showed that increasing the length of the chain in C3- and C5-ester substituents increased the activity and the most active compound was the diphenylethyl ester derivative, so it was more active than the reference drug nifedipine. In unsymmetrical diester series, when R1 is methyl or ethyl, increasing lipophilic properties in the R substituent, increased the activity. The most active compounds were methyl/phenethyl and ethyl/phenethyl ester derivatives, being slightly more active than nifedipine.
Davood
Asghar
A
Department of Medicinal Chemistry, Faculty of Pharmacy, Islamic Azad University, Tehran, Iran.
Mansouri
Niloufar
N
Rerza Dehpour
Ahmad
A
Shafaroudi
Hamed
H
Alipour
Eskandar
E
Shafiee
Abbas
A
D000818:Animals; D002121:Calcium Channel Blockers / Q000138:chemical synthesis* / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D004095:Dihydropyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D015195:Drug Design; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D015394:Molecular Structure; D009126:Muscle Relaxation; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D009543:Nifedipine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; D007093:Imidazoles; C038806:1,4-dihydropyridine; D009543:Nifedipine