186603-76-9Relevant academic research and scientific papers
Discovery of an orally-bioavailable CC Chemokine Receptor 2 antagonist derived from an acyclic diaminoalcohol backbone
Carter, Percy H.,Brown, Gregory D.,King, Sarah R.,Voss, Matthew E.,Tebben, Andrew J.,Cherney, Robert J.,Mandlekar, Sandhya,Lo, Yvonne C.,Yang, Gengjie,Miller, Persymphonie B.,Scherle, Peggy A.,Zhao, Qihong,Decicco, Carl P.
scheme or table, p. 3311 - 3316 (2012/06/18)
We describe an isostere-driven approach to improve upon a previously-described series of capped dipeptide antagonists of CC Chemokine Receptor 2 (CCR2). Modification of the substitution around the isostere was combined with additional changes in a distal
Capped diaminopropionamide-glycine dipeptides are inhibitors of CC chemokine receptor 2 (CCR2)
Carter, Percy H.,Brown, Gregory D.,Friedrich, Sarah R.,Cherney, Robert J.,Tebben, Andrew J.,Lo, Yvonne C.,Yang, Gengjie,Jezak, Heather,Solomon, Kimberly A.,Scherle, Peggy A.,Decicco, Carl P.
, p. 5455 - 5461 (2008/12/23)
A new series of CCR2 antagonists has been discovered that incorporates intramolecular hydrogen bonding as a strategy for rigidifying the scaffold. The structure-activity relationship was established through initial systematic modification of substitution pattern and chain length, followed by independent optimization of three different substituents (benzylamine, carboxamide, and benzamide). Several of the acyclic compounds display 10-30 nM binding affinity for CCR2. Moreover, these antagonists are able to block both MCP-1-induced Ca2+ flux and monocyte chemotaxis, and are selective for binding to CCR2 over CCR1 and CCR3.
