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ID: ALA4406910

Journal: ACS Med Chem Lett

Title: Scaffold Morphing Identifies 3-Pyridyl Azetidine Ureas as Inhibitors of Nicotinamide Phosphoribosyltransferase (NAMPT).

Authors: Palacios DS, Meredith EL, Kawanami T, Adams CM, Chen X, Darsigny V, Palermo M, Baird D, George EL, Guy C, Hewett J, Tierney L, Thigale S, Wang L, Weihofen WA.

Abstract: Small molecules that inhibit the metabolic enzyme NAMPT have emerged as potential therapeutics in oncology. As part of our effort in this area, we took a scaffold morphing approach and identified 3-pyridyl azetidine ureas as a potent NAMPT inhibiting motif. We explored the SAR of this series, including 5 and 6 amino pyridines, using a convergent synthetic strategy. This lead optimization campaign yielded multiple compounds with excellent in vitro potency and good ADME properties that culminated in compound 27.

CiteXplore: 31749905

DOI: 10.1021/acsmedchemlett.9b00325