In vitro and in vivo SAR of pyrido[3,4-d]pyramid-4-ylamine based mGluR1 antagonists.
The SAR of a series of novel pyrido[3,4-d]pyramid-4-ylamine mGluR1 antagonists is described. The multiple of the unbound K(i) in cerebrospinal fluid necessary to give morphine like analgesic effects in an electromyograph pinch model in rodents is determined and the effect of structure on CNS penetration examined.
Mantell
Simon J
SJ
Drug Discovery Group, Medical Research Council Technology, Mill Hill, London, United Kingdom. simon.mantell@pfizer.com
Gibson
Karl R
KR
Osborne
Simon A
SA
Maw
Graham N
GN
Rees
Huw
H
Dodd
Peter G
PG
Greener
Ben
B
Harbottle
Gareth W
GW
Million
William A
WA
Poinsard
Cedric
C
England
Steven
S
Carnell
Pauline
P
Betts
Alison M
AM
Monhemius
Russell
R
Prime
Rebecca L
RL
D000818:Animals; D004576:Electromyography / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors* / Q000502:physiology; D013329:Structure-Activity Relationship
D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1