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Discovery of a Potent and Orally Bioavailable Dual Antagonist of CC Chemokine Receptors 2 and 5.

ACS Med Chem Lett; 6(4): 439-44, 2015 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-25893046
We describe the hybridization of our previously reported acyclic and cyclic CC chemokine receptor 2 (CCR2) antagonists to lead to a new series of dual antagonists of CCR2 and CCR5. Installation of a γ-lactam as the spacer group and a quinazoline as a benzamide mimetic improved oral bioavailability markedly. These efforts led to the identification of 13d, a potent and orally bioavailable dual antagonist suitable for use in both murine and monkey models of inflammation.