2,4-Dicarboxy-pyrroles as selective non-competitive mGluR1 antagonists: further characterization of 3,5-dimethyl pyrrole-2,4-dicarboxylic acid 2-propyl ester 4-(1,2,2-trimethyl-propyl) ester and structure-activity relationships.
Following the disclosure of 3,5-dimethyl pyrrole-2,4-dicarboxylic acid 2-propyl ester 4-(1,2,2-trimethyl-propyl) ester [3,5-dimethyl PPP] as a potent and selective mGluR1 non-competitive antagonist, we report here further in vivo characterization of this important tool and disclose the investigation of the C-5 position, which led to very potent compounds.
Micheli
Fabrizio
F
GlaxoSmithKline Medicine Research Centre, Via Fleming 4, 37135, Verona, Italy. fabio@gsk.com
Di Fabio
Romano
R
Bordi
Fabio
F
Cavallini
Palmina
P
Cavanni
Paolo
P
Donati
Daniele
D
Faedo
Stefania
S
Maffeis
Micaela
M
Sabbatini
Fabio Maria
FM
Tarzia
Giorgio
G
Tranquillini
Maria Elvira
ME
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D004952:Esters / Q000138:chemical synthesis* / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D009020:Morphine / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects; D011758:Pyrroles / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship; D009435:Synaptic Transmission / Q000187:drug effects; D013788:Thalamus / Q000187:drug effects / Q000378:metabolism
C481958:3,5-dimethyl pyrrole-2,4-dicarboxylic acid 2-propyl ester 4-(1,2,2-trimethyl-propyl) ester; D004952:Esters; D018691:Excitatory Amino Acid Antagonists; D007202:Indicators and Reagents; D011758:Pyrroles; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D009020:Morphine