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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Novel, orally bioavailable gamma-aminoamide CC chemokine receptor 2 (CCR2) antagonists.

Through modification of a screening hit we have discovered a structurally distinct new lead, (2S)-N-[3,5-bis(trifluoromethyl)benzyl]-2-(4-fluorophenyl)-4-(4-phenylpiperidin-1-yl)butanamide (11), which has subsequently served as the departure point for an ongoing program targeting CCR2 antagonists. Optimization of 11 leading to antagonists 26 and 37 is described. Antagonist 26 was shown to have good oral bioavailability in rats. Antagonist 37 had a CCR2 IC50 of 59 nM and excellent potency in a functional assay measuring inhibition of MCP-1 induced monocyte chemotaxis (IC50 of 41 nM).[1]

References

  1. Novel, orally bioavailable gamma-aminoamide CC chemokine receptor 2 (CCR2) antagonists. Pasternak, A., Marino, D., Vicario, P.P., Ayala, J.M., Cascierri, M.A., Parsons, W., Mills, S.G., Maccoss, M., Yang, L. J. Med. Chem. (2006) [Pubmed]
 
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