Benzopyrimidodiazepinone inhibitors of TNK2

  • Bioorg Med Chem Lett. 2020 Feb 15;30(4):126948. doi: 10.1016/j.bmcl.2020.126948.
Brian J Groendyke  1 ,  Chelsea E Powell  1 ,  Frederic Feru  1 ,  Thomas W Gero  1 ,  Zhengnian Li  1 ,  Hilary Szabo  2 ,  Kevin Pang  3 ,  John Feutrill  4 ,  Bailing Chen  4 ,  Bin Li  4 ,  Nathanael S Gray  1 ,  David A Scott  1
Affiliations
  • 1. Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, 360 Longwood Ave, Boston, MA 02115, USA.
  • 2. Vivid BioSciences, 50 Northern Ave, Boston, MA 02210, USA.
  • 3. Northeastern University, 360 Huntington Ave, Boston, MA 02115, USA.
  • 4. SYNthesis Med Chem, 425 Changyang Street, Suzhou Industry Park, Suzhou, Jiangsu, China.
PMID: 31928839 DOI: 10.1016/j.bmcl.2020.126948
Abstract

The SAR of a series of benzopyrimidodiazepinone inhibitors of TNK2 was developed, starting from the potent and selective compound XMD8-87. A diverse set of anilines was introduced in an effort to improve the in vivo PK profile and minimize the risk of quinone diimine formation.

Keywords
Benzopyrimidodiazepinone; Kinase inhibitor; TNK2.