Small, non-peptide C5a receptor antagonists: part 1.
The optimisation of a series of amides for C5a receptor binding and functional activity, and physicochemical properties is described. The initial hit, 1 (IC(50) 1 microM), was discovered during high throughput screening, from which highly potent C5a receptor antagonists (e.g.14, IC(50) 5 nM) were developed.
Blagg
Julian
J
Department of Discovery Chemistry, Pfizer Global Research and Development, Ramsgate Road, Sandwich, Kent CT13 9NJ, UK.
Mowbray
Charles
C
Pryde
David C
DC
Salmon
Gary
G
Schmid
Esther
E
Fairman
David
D
Beaumont
Kevin
K
D000284:Administration, Oral; D002021:Buffers; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015936:Complement C5a / Q000037:antagonists & inhibitors* / Q000737:chemistry; D015195:Drug Design; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D020128:Inhibitory Concentration 50; D008862:Microsomes, Liver / Q000378:metabolism; D008956:Models, Chemical; D010455:Peptides / Q000737:chemistry*; D010880:Piperidines / Q000737:chemistry; D011485:Protein Binding
D002021:Buffers; D010455:Peptides; D010880:Piperidines; D015936:Complement C5a