Title of article :
Structure–activity relationships of novel, highly potent, selective, and orally active CCR1 antagonists
Author/Authors :
Yun-Feng Xie، نويسنده , , Kirk Lake، نويسنده , , Kathleen Ligsay، نويسنده , , Mallareddy Komandla، نويسنده , , Ila Sircar، نويسنده , , Gobi Nagarajan، نويسنده , , Jian Li، نويسنده , , Kui Xu، نويسنده , , Jason Parise، نويسنده , , Lisa Schneider، نويسنده , , Dinq-Ding Huang، نويسنده , , Juping Liu، نويسنده , , Kevin Dines، نويسنده , , Naoki Sakurai، نويسنده , , Miguel Barbosa، نويسنده , , Rick Jack، نويسنده ,
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.
