2,3'-disubstituted-2-(2'-carboxycyclopropyl)glycines as potent and selective antagonists of metabotropic glutamate receptors.
2-(9-Xanthylmethyl)-2-(2'-carboxycyclopropyl) glycine 6e is a novel metabotropic glutamate receptor antagonist. A series of alpha, C-3' disubstituted (carboxycyclopropyl)glycines 6f-n were prepared. Antagonist activity was observed for all these compounds at group 2 and group 3 mGluRs. Although they were slightly less active on group 2 mGluRs than non C-3' substituted 6e, the compounds 6f-n were more selective with lesser or no activity on group 1 mGluR subtypes (IC50 values greater than 100 microns).
Collado
I
I
Centro de Investigación Lilly, SA, Madrid, Spain.
Ezquerra
J
J
Mazón
A
A
Pedregal
C
C
Yruretagoyena
B
B
Kingston
A E
AE
Tomlinson
R
R
Wright
R A
RA
Johnson
B G
BG
Schoepp
D D
DD
D000818:Animals; D002460:Cell Line; D003521:Cyclopropanes / Q000737:chemistry / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D009474:Neurons / Q000187:drug effects; D016548:Prosencephalon / Q000187:drug effects; D051381:Rats; D017470:Receptors, Glutamate / Q000187:drug effects*; D013329:Structure-Activity Relationship
D003521:Cyclopropanes; D018691:Excitatory Amino Acid Antagonists; D017470:Receptors, Glutamate; D005998:Glycine