Discovery of 2-hydroxy-N,N-dimethyl-3-{2-[[(R)-1-(5- methylfuran-2-yl)propyl]amino]-3,4-dioxocyclobut-1-enylamino}benzamide (SCH 527123): a potent, orally bioavailable CXCR2/CXCR1 receptor antagonist

  • J Med Chem. 2006 Dec 28;49(26):7603-6. doi: 10.1021/jm0609622.
Michael P Dwyer  1 ,  Younong Yu ,  Jianping Chao ,  Cynthia Aki ,  Jianhua Chao ,  Purakkattle Biju ,  Viyyoor Girijavallabhan ,  Diane Rindgen ,  Richard Bond ,  Rosemary Mayer-Ezel ,  James Jakway ,  R William Hipkin ,  James Fossetta ,  Waldemar Gonsiorek ,  Hong Bian ,  Xuedong Fan ,  Carol Terminelli ,  Jay Fine ,  Daniel Lundell ,  J Robert Merritt ,  Laura L Rokosz ,  Bernd Kaiser ,  Ge Li ,  Wei Wang ,  Tara Stauffer ,  Lynne Ozgur ,  John Baldwin ,  Arthur G Taveras
Affiliations
  • 1. Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. [email protected]
PMID: 17181143 DOI: 10.1021/jm0609622
Abstract

Structure-activity studies on lead cyclobutenedione 3 led to the discovery of 4 (SCH 527123), a potent, orally bioavailable CXCR2/CXCR1 receptor antagonist with excellent cell-based activity. Compound 4 displayed good oral bioavailability in rat and may be a potential therapeutic agent for the treatment of various inflammatory diseases.