Structure-activity relationships of novel non-competitive mGluR1 antagonists: a potential treatment for chronic pain.
A series of novel mGluR1 antagonists have been prepared. Incorporation of fragments derived from weak lead matter into a library led to enhanced potency in a new chemical series. A chemistry driven second library iteration, covering a greatly enhanced area of chemical space, maintained good potency and introduced metabolic stability.
Owen
Dafydd R
DR
Pfizer Global Research and Development, Ramsgate Road, Sandwich, CT13 9NJ, UK. dafydd.owen@pfizer.com
Dodd
Peter G
PG
Gayton
Simon
S
Greener
Ben S
BS
Harbottle
Gareth W
GW
Mantell
Simon J
SJ
Maw
Graham N
GN
Osborne
Simon A
SA
Rees
Huw
H
Ringer
Tracy J
TJ
Rodriguez-Lens
Margarita
M
Smith
Graham F
GF
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D016466:CHO Cells; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002908:Chronic Disease; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy*; D011719:Pyrazines / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D011719:Pyrazines; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D018698:Glutamic Acid