Discovery of a Potent and Orally Bioavailable Dual Antagonist of CC Chemokine Receptors 2 and 5.
Basic Information
ID: ALA3576800
Journal: ACS Med Chem Lett
Title: Discovery of a Potent and Orally Bioavailable Dual Antagonist of CC Chemokine Receptors 2 and 5.
Authors: Carter PH, Brown GD, Cherney RJ, Batt DG, Chen J, Clark CM, Cvijic ME, Duncia JV, Ko SS, Mandlekar S, Mo R, Nelson DJ, Pang J, Rose AV, Santella JB, Tebben AJ, Traeger SC, Xu S, Zhao Q, Barrish JC.
Abstract: 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.
CiteXplore: 25893046
DOI: 10.1021/ml500505q
Patent ID: ┄