2,3-Ethylene- and 2,3-trimethylene-bridged analogues of the group III metabotropic glutamate receptor ligand 2-amino-4-phosphonobutanoic acid.
The racemic trans- and cis-isomers of 1-amino-2-phosphonomethyl-cyclobutanecarboxylic acid (5 and 6) and 1-amino-2-phosphonomethyl-cyclopentanecarboxylic acid (7 and 8) were synthesized as extensions of the mGluR4 agonists trans- and cis-1-amino-2-phosphonomethyl-cyclopropanecarboxylic acid (3 and 4). Although the methylene bridge in 3 and 4 allows for retention of affinity toward the mGluR4 receptor, increasing the bridging unit to the ethylene group as in 5 and 6 or to the trimethylene group as in 7 and 8 introduces sufficient steric hindrance to eliminate affinity for the mGluR4 receptor.
Johnson
Rodney L
RL
Department of Medicinal Chemistry, University of Minnesota, 308 Harvard Street SE, Minneapolis, MN 55455, USA. johns022@umn.edu
Rao
Kolluri S S P
KS
D000613:Aminobutyrates / Q000378:metabolism*; D018360:Crystallography, X-Ray; D003521:Cyclopropanes / Q000737:chemistry*; D005030:Ethylenes / Q000737:chemistry*; D008024:Ligands; D008958:Models, Molecular; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*
D000613:Aminobutyrates; D003521:Cyclopropanes; D005030:Ethylenes; D008024:Ligands; D018094:Receptors, Metabotropic Glutamate; C036216:ethylene; C030797:cyclopropane; C012729:2-amino-4-phosphonobutyric acid