Tricyclic thienopyridine-pyrimidones/thienopyrimidine-pyrimidones as orally efficacious mGluR1 antagonists for neuropathic pain.
Introduction of small unsaturated alkylamino groups at the 4-position of the A-ring of the tricyclic framework (triazafluorenone) afforded extremely potent and selective mGluR1 antagonists with desirable properties. Compounds 11q and 11s are active in the SNL pain model with ED(50)s 3.3 and 6.4 mg/kg respectively. Metabolic outcome of propargyl amino moiety was studied.
Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. sasikumartk@yahoo.com
T K
TK
Sasikumar
Li
L
Qiang
Duane A
DA
Burnett
William J
WJ
Greenlee
Cheng
C
Li
Larry
L
Heimark
Birendra
B
Pramanik
Mariagrazia
M
Grilli
Rosalia
R
Bertorelli
Gianluca
G
Lozza
Angelo
A
Reggiani
D000284:Administration, Oral; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006575:Heterocyclic Compounds, 3-Ring / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D009437:Neuralgia / Q000188:drug therapy*; D011725:Pyridines / Q000737:chemistry* / Q000494:pharmacology; D011743:Pyrimidines / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D006575:Heterocyclic Compounds, 3-Ring; D011725:Pyridines; D011743:Pyrimidines; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; C446540:thienopyridine; C476003:thienopyrimidine