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Bioorg Med Chem Lett. 2007 Jul 1;17(13):3778-83. Epub 2007 Apr 10.

C(4)-alkyl substituted furanyl cyclobutenediones as potent, orally bioavailable CXCR2 and CXCR1 receptor antagonists.

Author information

1
Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. jianhua.chao@spcorp.com <jianhua.chao@spcorp.com>

Abstract

A novel series of cyclobutenedione centered C(4)-alkyl substituted furanyl analogs was developed as potent CXCR2 and CXCR1 antagonists. Compound 16 exhibits potent inhibitory activities against IL-8 binding to the receptors (CXCR2 Ki=1 nM, IC(50)=1.3 nM; CXCR1 Ki=3 nM, IC(50)=7.3 nM), and demonstrates potent inhibition against both Gro-alpha and IL-8 induced hPMN migration (chemotaxis: CXCR2 IC(50)=0.5 nM, CXCR1 IC(50)=37 nM). In addition, 16 has shown good oral pharmacokinetic profiles in rat, mouse, monkey, and dog.

PMID:
17459706
DOI:
10.1016/j.bmcl.2007.04.016
[Indexed for MEDLINE]

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