Structure-activity relationships of novel, highly potent, selective, and orally active CCR1 antagonists

  • Bioorg Med Chem Lett. 2007 Jun 15;17(12):3367-72. doi: 10.1016/j.bmcl.2007.03.104.
Yun Feng Xie  1 ,  Kirk Lake ,  Kathleen Ligsay ,  Mallareddy Komandla ,  Ila Sircar ,  Gobi Nagarajan ,  Jian Li ,  Kui Xu ,  Jason Parise ,  Lisa Schneider ,  Ding Huang ,  Juping Liu ,  Kevin Dines ,  Naoki Sakurai ,  Miguel Barbosa ,  Rick Jack
Affiliations
  • 1. Department of Chemistry, Tanabe Research Laboratories, Inc., 4540 Towne Centre Court, San Diego, CA 92121, USA.
PMID: 17446072 DOI: 10.1016/j.bmcl.2007.03.104
Abstract

Design and synthesis of a series of 3-amino-4-(2-(2-(4-benzylpiperazin-1-yl)-2-oxoethoxy)phenylamino)cyclobutenedione derivatives as novel CCR1 antagonists are described. Structure-activity relationship studies led to the identification of compound 22, which demonstrated potent binding activity, functional antagonism of CCR1 as well as good species cross-reactivity. In addition, compound 22 also showed desirable pharmacokinetic profiles and was selected for in vivo studies in the mouse collagen-induced arthritis model.