Overcoming HERG affinity in the discovery of the CCR5 antagonist maraviroc.
The discovery of maraviroc 17 is described with particular reference to the generation of high selectivity over affinity for the HERG potassium channel. This was achieved through the use of a high throughput binding assay for the HERG channel that is known to show an excellent correlation with functional effects.
Price
David A
DA
Pfizer Global Research and Development, Sandwich Laboratories, Sandwich, Kent, UK. david.a.price@pfizer.com
Armour
Duncan
D
de Groot
Marcel
M
Leishman
Derek
D
Napier
Carolyn
C
Perros
Manos
M
Stammen
Blanda L
BL
Wood
Anthony
A
D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology; D065100:CCR5 Receptor Antagonists; D002460:Cell Line; D054407:Chemokine CCL4; D051638:Ether-A-Go-Go Potassium Channels / Q000378:metabolism*; D006678:HIV / Q000187:drug effects; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D019713:Receptors, CCR5 / Q000378:metabolism; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D065100:CCR5 Receptor Antagonists; D054407:Chemokine CCL4; D051638:Ether-A-Go-Go Potassium Channels; D019402:Macrophage Inflammatory Proteins; D019713:Receptors, CCR5