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Bioorg Med Chem Lett. 2012 Jan 1;22(1):357-62. doi: 10.1016/j.bmcl.2011.10.120. Epub 2011 Nov 9.

Discovery of potent and specific CXCR3 antagonists.

Author information

1
Amgen Inc., 1120 Veterans Boulevard, ASF2-3, South San Francisco, CA 94080, USA. xiaoqic@amgen.com

Abstract

The optimization of a series of 8-aza-quinazolinone analogs for antagonist activity against the CXCR3 receptor is reported. Compounds were optimized to avoid the formation of active metabolites and time-dependent-inhibitors of CYP3A4. In addition, antagonists showed potent against CXCR3 activity in whole blood and optimized to avoid activity in the chromosomal aberration assay. Compound 25 was identified as having the optimal balance of CXCR3 activity and pharmacokinetic properties across multiple pre-clinical species, which are reported herein.

PMID:
22130135
DOI:
10.1016/j.bmcl.2011.10.120
[Indexed for MEDLINE]

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