Hit-to-Lead studies: the discovery of potent adamantane amide P2X7 receptor antagonists.
A Hit-to-Lead optimisation programme was carried out on the adamantane high throughput screening hit 1 resulting in the discovery of a number of potent P2X(7) antagonists.
Baxter
Andrew
A
AstraZeneca R&D Charnwood, Bakewell Road, Loughborough LE11 5RH, UK. andrew.jg.baxter@astrazeneca.com
Bent
Janice
J
Bowers
Keith
K
Braddock
Martin
M
Brough
Steve
S
Fagura
Malbinder
M
Lawson
Mandy
M
McInally
Tom
T
Mortimore
Mike
M
Robertson
Mark
M
Weaver
Richard
R
Webborn
Peter
P
D000218:Adamantane / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D000577:Amides / Q000138:chemical synthesis / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D007700:Kinetics; D058919:Purinergic P2 Receptor Antagonists; D058486:Receptors, Purinergic P2X7; D013329:Structure-Activity Relationship
D000577:Amides; C546468:P2RX7 protein, human; D058919:Purinergic P2 Receptor Antagonists; D058486:Receptors, Purinergic P2X7; D000218:Adamantane