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The discovery of BMS-457, a potent and selective CCR1 antagonist.

Authors :
Gardner DS
Santella JB 3rd
Duncia JV
Carter PH
Dhar TG
Wu H
Guo W
Cavallaro C
Van Kirk K
Yarde M
Briceno SW
Grafstrom RR
Liu R
Patel SR
Tebben AJ
Camac D
Khan J
Watson A
Yang G
Rose A
Foster WR
Cvijic ME
Davies P
Hynes J Jr
Source :
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2013 Jul 01; Vol. 23 (13), pp. 3833-40. Date of Electronic Publication: 2013 May 07.
Publication Year :
2013

Abstract

A series of compounds which exhibited good human CCR1 binding and functional potency was modified resulting in the discovery of a novel series of high affinity, functionally potent antagonists of the CCR1 receptor. Issues of PXR activity, ion-channel potency, and poor metabolic stability were addressed by the addition of a hydroxyl group to an otherwise lipophilic area in the molecule resulting in the discovery of preclinical candidate BMS-457 for the treatment of rheumatoid arthritis.<br /> (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Details

Language :
English
ISSN :
1464-3405
Volume :
23
Issue :
13
Database :
MEDLINE
Journal :
Bioorganic & medicinal chemistry letters
Publication Type :
Academic Journal
Accession number :
23707259
Full Text :
https://doi.org/10.1016/j.bmcl.2013.04.079