Synthesis and evaluation of pharmacological activities of 3, 5-dialkyl 1, 4-dihydro-2,6-dimethyl-4-nitroimidazole-3, 5-pyridine dicarboxylates.
New analogues of nifedipine, in which the 2-nitrophenyl group at position 4 is replaced by a 1-methyl-5-nitro-2-imidazolyl substituent, were synthesized. The symmetrical dialkyl 1, 4-dihydro-2, 6-dimethyl-4-(1-methyl-5-nitro-2-imidazolyl)-3, 5-pyridinedicarboxylates were prepared by a classical Hantzsch condensation. The asymmetrical analogues were synthesized using a procedure reported by Iwanami that involved the condensation of alkylacetoacetate with methyl-, ethyl- or isopropyl3-aminocrotonate and 1-methyl-5-nitroimidazole-2-carboxaldehyde. Calcium channel antagonist activities were determined in vitro using a guinea pig ileum longitudinal smooth muscle (GPILSM)assay. Many compounds exhibited superior, or equipotent, calcium antagonist activity (IC(50) = 10(-10) to 10(-13) M range) relative to the reference drug nifedipine (IC(50) = 1.09 +/- 0.12 x 10(-11) M). Antinociceptive effects of some compounds were evaluated by the mouse tail-flick assay in vivo. Results demonstrate that some of the compounds were active as an antinociceptive.
Miri
Ramin
R
Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Science, Shiraz, Iran. mirir@sums.ac.ir
Javidnia
K
K
Kebriaie-Zadeh
A
A
Niknahad
H
H
Shaygani
N
N
Semnanian
S
S
Shafiee
A
A
D000700:Analgesics / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000138:chemical synthesis / Q000494:pharmacology*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009593:Nitroimidazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D010147:Pain Measurement; D011725:Pyridines / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013623:Tail
D000700:Analgesics; D002121:Calcium Channel Blockers; D009593:Nitroimidazoles; D011725:Pyridines