(2R,1'S,2'R,3'S)-2-(2'-Carboxy-3'-phenylcyclopropyl)glycine (PCCG-13), the first potent and selective competitive antagonist of phospholipase D-coupled metabotropic glutamate receptors: asymmetric synthesis and preliminary biological properties.
The asymmetric synthesis of (2R,1'S,2'R, 3'S)-2-(2'-carboxy-3'-phenylcyclopropyl)glycine (PCCG-13), a trisubstituted carboxycyclopropylglycine endowed with unusual stereochemical features, is described. Preliminary biological evaluation demonstrates PCCG-13 as a very potent and selective competitive antagonist for the novel class of metabotropic glutamate (mGlu) receptors coupled to the activity of phospholipase D (PLD). PCCG-13 is therefore a useful tool for the exploration of the physiopathological role of this novel class of receptors.
Pellicciari
R
R
Istituto di Chimica e Tecnologia del Farmaco, Università di Perugia, Via del Liceo, 1-06123 Perugia, Italy. rp@unipg.it
Marinozzi
M
M
Costantino
G
G
Natalini
B
B
Moroni
F
F
Pellegrini-Giampietro
D
D
D000818:Animals; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D003521:Cyclopropanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020404:Glycerophospholipids / Q000096:biosynthesis; D005998:Glycine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D010739:Phospholipase D / Q000378:metabolism*; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013237:Stereoisomerism; D010738:Type C Phospholipases / Q000378:metabolism
C099854:2-(2'-carboxy-3'-phenylcyclopropyl)glycine; D003521:Cyclopropanes; D020404:Glycerophospholipids; D018094:Receptors, Metabotropic Glutamate; C051521:phosphatidylethanol; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D010738:Type C Phospholipases; D010739:Phospholipase D; D005998:Glycine