Novel P2X7 receptor antagonists.
The synthesis and pharmacological evaluation of a new series of potent P2X(7) receptor antagonists is disclosed. The compounds inhibit BzATP-mediated pore formation in THP-1 cells. The distribution of the P2X(7) receptor in inflammatory cells, most notably the macrophage, mast cell and lymphocyte, suggests that P2X(7) antagonists have a significant role to play in the treatment of inflammatory disease.
Department of Medicinal Chemistry, AstraZeneca R&D Charnwood, Bakewell Road, Loughborough LE11 5RH, UK. alcaraz@astrazeneca.com
L
L
Alcaraz
A
A
Baxter
J
J
Bent
K
K
Bowers
M
M
Braddock
D
D
Cladingboel
D
D
Donald
M
M
Fagura
M
M
Furber
C
C
Laurent
M
M
Lawson
M
M
Mortimore
M
M
McCormick
N
N
Roberts
M
M
Robertson
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D002460:Cell Line; D006801:Humans; D007700:Kinetics; D015394:Molecular Structure; D058919:Purinergic P2 Receptor Antagonists; D058486:Receptors, Purinergic P2X7; D013329:Structure-Activity Relationship
C546468:P2RX7 protein, human; D058919:Purinergic P2 Receptor Antagonists; D058486:Receptors, Purinergic P2X7; C033901:3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; D000255:Adenosine Triphosphate