TY - JOUR
T1 - Bicyclic lactones derived from kainic acid as novel selective antagonists of neuroexcitatory amino acids
AU - Goldberg, Ora
AU - Luini, Alberto
AU - Teichberg, Vivian I.
PY - 1983
Y1 - 1983
N2 - The bicyclic [2S-(2α,3β,4β)]-2-carboxy-4-(1-hydroxy-1-methylethyl)-3- pyrrolidineacetic acid 5-lactone (4), as well as its 4-[1-hydroxy-1-(iodomethyl)ethyl], 4-[1-hydroxy-1-(hydroxymethyl)ethyl], and 4-[1-hydroxy-1-[(phenylthio)methyl]ethyl] analogues, 6, 7, and 9, respectively, were designed and synthesized as potential selective antagonists of neuroexcitatory amino acids. When applied to rat brain slices, these lactones, which are chemically derived from kainic acid, inhibit the stimulation of Na+ fluxes induced by the neuroexcitants kainic acid and N-methyl-D-aspartic acid. Lactone 4 and the hydroxy lactone 7 block preferentially the response to N-methyl-D-aspartic acid, while the iodo lactone 6 and the phenylthio lactone 9 are mainly kainic acid antagonists. Total inhibitions can be obtained, half of the maximal effect being observed at lactone concentrations in the range of 0.2-3 mM.
AB - The bicyclic [2S-(2α,3β,4β)]-2-carboxy-4-(1-hydroxy-1-methylethyl)-3- pyrrolidineacetic acid 5-lactone (4), as well as its 4-[1-hydroxy-1-(iodomethyl)ethyl], 4-[1-hydroxy-1-(hydroxymethyl)ethyl], and 4-[1-hydroxy-1-[(phenylthio)methyl]ethyl] analogues, 6, 7, and 9, respectively, were designed and synthesized as potential selective antagonists of neuroexcitatory amino acids. When applied to rat brain slices, these lactones, which are chemically derived from kainic acid, inhibit the stimulation of Na+ fluxes induced by the neuroexcitants kainic acid and N-methyl-D-aspartic acid. Lactone 4 and the hydroxy lactone 7 block preferentially the response to N-methyl-D-aspartic acid, while the iodo lactone 6 and the phenylthio lactone 9 are mainly kainic acid antagonists. Total inhibitions can be obtained, half of the maximal effect being observed at lactone concentrations in the range of 0.2-3 mM.
UR - http://www.scopus.com/inward/record.url?scp=0020615825&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0020615825&partnerID=8YFLogxK
M3 - Article
C2 - 6827527
AN - SCOPUS:0020615825
VL - 26
SP - 39
EP - 42
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 1
ER -