53219-30-0Relevant articles and documents
Synthesis and calcium channel antagonist activity of dialkyl hexahydro-1,2',6'-trimethyl-3',5'-dicarboxylates
Dagnino, Lina,Li-Kwong-Ken, Moy Cheong,Wolowyk, Michael W.,Triggle, Christopher R.,Knaus, Edward E.
, p. 499 - 504 (2007/10/02)
Reaction of dialkyl 1',4'-dihydro-2',6'-dimethyl-3',5'-dicarboxylates 2 with methyl iodide yielded the corresponding 4'-(1-methylpyridinium) iodide salts 3 in quantitative yield.The sodium borohydride reduction of 3 in aqueous ethanol gave the corresponding dialkyl hexahydro-1,2',6'-trimethyl-3',5'-dicarboxylate analogs 4-5.The calcium channel antagonist activities for 4-5 were determined using the muscarinic receptor-mediated Ca2+-dependent contraction of guinea pig ileal longitudinal smooth muscle.The relative activities for the 3',5'-diethyl series 5 was 3-tetrahydropyridinyl 5b>4-tetrahydropyridinyl 5c > 2-tetrahydropyridinyl 5a.Increasing the size of the 3',5'-alkyl substituents enhanced activity.An approximate 1:1 correlation between the IC50 value for the inhibition of 3H>nitrendipine binding and inhibition of the tonic component of the muscarinic-induced contractile response was observed for 4a and 5b.NMR studies suggest that the 4'- ring systems of 4a and 5a are anti-periplaner to the 1,4-dihydropyridine ring system.
