Discovery of a novel series of CXCR3 antagonists.
The discovery of a novel series of CXCR3 antagonists is described. Starting from an HTS positive, iterative optimization gave potent compounds (IC(50) 15 nM in a chemotaxis assay). The strategy employed to improve the metabolic stability of these derivatives is described.
Crosignani
Stefano
S
Merck Serono SA, Geneva, Switzerland. stefano.crosignani@merckserono.net
Missotten
Marc
M
Cleva
Christophe
C
Dondi
Ruggero
R
Ratinaud
Yann
Y
Humbert
Yves
Y
Mandal
Ashis Baran
AB
Bombrun
Agnès
A
Power
Christine
C
Chollet
André
A
Proudfoot
Amanda
A
D000818:Animals; D002460:Cell Line; D002633:Chemotaxis / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008861:Microsomes; D051381:Rats; D054367:Receptors, CXCR3 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000502:physiology
D054367:Receptors, CXCR3