Diverse heterocyclic scaffolds as dCTP pyrophosphatase 1 inhibitors. Part 2: Pyridone- and pyrimidinone-derived systems

Bioorg Med Chem Lett. 2017 Aug 1;27(15):3219-3225. doi: 10.1016/j.bmcl.2017.06.039. Epub 2017 Jun 15.

Abstract

Two screening campaigns using commercial (Chembridge DiverSET) and proprietary (Chemical Biology Consortium Sweden, CBCS) compound libraries, revealed a number of pyridone- and pyrimidinone-derived systems as inhibitors of the human dCTP pyrophosphatase 1 (dCTPase). In this letter, we present their preliminary structure-activity-relationships (SAR) and ligand efficiency scores (LE and LLE).

Keywords: DCTPP1; Nucleotide metabolism; Pyridone; Pyrimidone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Ligands
  • Pyridones / chemistry*
  • Pyridones / pharmacology*
  • Pyrimidinones / chemistry*
  • Pyrimidinones / pharmacology*
  • Pyrophosphatases / antagonists & inhibitors*
  • Pyrophosphatases / metabolism
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Ligands
  • Pyridones
  • Pyrimidinones
  • Pyrophosphatases
  • dCTP pyrophosphatase