Novel pyrrolidine heterocycles as CCR1 antagonists.
A novel series of pyrrolidine heterocycles was prepared and found to show potent inhibitory activity of CCR1 binding and CCL3 mediated chemotaxis of a CCR1-expressing cell line. A potent, optimized triazole lead from this series was found to have acceptable pharmacokinetics and microsomal stability in rat and is suitable for further optimization and development.
Merritt
J Robert
JR
Ligand Pharmaceuticals, Inc., 3000 Eastpark Blvd., Cranbury, NJ 08512, USA. jmerritt@kean.edu
James
Ray
R
Paradkar
Vidyadhar M
VM
Zhang
Chongwu
C
Liu
Ruiyan
R
Liu
Jinqi
J
Jacob
Biji
B
Chiriac
Camelia
C
Ohlmeyer
Michael J
MJ
Quadros
Elizabeth
E
Wines
Pamela
P
Postelnek
Jennifer
J
Hicks
Catherine M
CM
Chen
Weiqing
W
Kimble
Earl F
EF
O'Brien
Linda
L
White
Nicole
N
Desai
Hema
H
Appell
Kenneth C
KC
Webb
Maria L
ML
D000818:Animals; D002460:Cell Line; D054405:Chemokine CCL3 / Q000276:immunology*; D002633:Chemotaxis / Q000187:drug effects*; D008862:Microsomes, Liver / Q000378:metabolism; D011759:Pyrrolidines / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D054389:Receptors, CCR1 / Q000037:antagonists & inhibitors* / Q000276:immunology; D014230:Triazoles / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology
D054405:Chemokine CCL3; D011759:Pyrrolidines; D054389:Receptors, CCR1; D014230:Triazoles; C032519:pyrrolidine