2. Academic Validation
  3. Scaffold Morphing Identifies 3-Pyridyl Azetidine Ureas as Inhibitors of Nicotinamide Phosphoribosyltransferase (NAMPT)

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

  • ACS Med Chem Lett. 2019 Oct 10;10(11):1524-1529. doi: 10.1021/acsmedchemlett.9b00325.
Daniel S Palacios 1,  Erik L Meredith 1,  Toshio Kawanami 1,  Christopher M Adams 1,  Xin Chen 1,  Veronique Darsigny 1,  Mark Palermo 1,  Daniel Baird 2,  Elizabeth L George 2,  Chantale Guy 2,  Jeffrey Hewett 2,  Laryssa Tierney 2,  Sachin Thigale 2,  Louis Wang 2,  Wilhelm A Weihofen 2
Affiliations

Affiliations

  • 1 Global Discovery Chemistry, Novartis Institute for Biomedical Research, 22 Windsor Street, Cambridge, Massachusetts 02139, United States.
  • 2 Chemical Biology and Therapeutics, Novartis Institute for Biomedical Research, 181 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
PMID: 31749905 DOI: 10.1021/acsmedchemlett.9b00325
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.

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