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

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

  • Bioorg Med Chem Lett. 2007 Jul 1;17(13):3778-83. doi: 10.1016/j.bmcl.2007.04.016.
Jianhua Chao " href="affiliation-1" ref="linksrc=author_aff"> # 1,  Arthur G Taveras,  Jianping Chao,  Cynthia Aki,  Michael Dwyer,  Younong Yu,  Biju Purakkattle,  Diane Rindgen,  James Jakway,  William Hipkin,  James Fosetta,  Xuedong Fan,  Daniel Lundell,  Jay Fine,  Michael Minnicozzi,  Jonathan Phillips,  J Robert Merritt
Affiliations

Affiliation

  • 1 Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. jianhua.chao@spcorp.com
  • # Contributed equally.
PMID: 17459706 DOI: 10.1016/j.bmcl.2007.04.016
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.

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