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.
Alcaraz
L
L
Department of Medicinal Chemistry, AstraZeneca R&D Charnwood, Bakewell Road, Loughborough LE11 5RH, UK. alcaraz@astrazeneca.com
Baxter
A
A
Bent
J
J
Bowers
K
K
Braddock
M
M
Cladingboel
D
D
Donald
D
D
Fagura
M
M
Furber
M
M
Laurent
C
C
Lawson
M
M
Mortimore
M
M
McCormick
M
M
Roberts
N
N
Robertson
M
M
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