Synthesis of 6-amino-1,4-dihydropyridines that prevent calcium overload and neuronal death

The synthesis and pharmacology of 6-amino-1,4-dihydropyridines, such as ethyl 6-amino-4-aryl-5-cyano-1,4-dihydro-2-methyl-3-pyridinecarboxylic acids (3-16) and 2-amino-4-aryl-7,7-dimethyl-5-oxo-1,4,5,6,7,8-hexahydro-3-quinolinenitriles (17-21) are described. Compounds 18 and 21, at the concentration of 0.3 mu M, proved to be the best blockers of the [Ca2+] overload induced by depolarization with high [K+] of SH-SY5Y neuroblastoma cells, with values of 63.8% and 50.4%, respectively. Most of the compounds induced a remarkable neuroprotective effect against toxicity caused by high [K+]-elicited [Ca2+] overload, and against H2O2-generated free radicals, in SH-SY5Y cells. (c) 2007 Elsevier Masson SAS. All rights reserved.