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ID: ALA1148011

Journal: Bioorg Med Chem Lett

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

Authors: Xie YF, Lake K, Ligsay K, Komandla M, Sircar I, Nagarajan G, Li J, Xu K, Parise J, Schneider L, Huang D, Liu J, Dines K, Sakurai N, Barbosa M, Jack R.

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.

CiteXplore: 17446072

DOI: 10.1016/j.bmcl.2007.03.104