Diverse heterocyclic scaffolds as dCTP pyrophosphatase 1 inhibitors. Part 1: Triazoles, triazolopyrimidines, triazinoindoles, quinoline hydrazones and arylpiperazines

Bioorg Med Chem Lett. 2017 Aug 15;27(16):3897-3904. doi: 10.1016/j.bmcl.2017.06.038. Epub 2017 Jun 16.

Abstract

A high-throughput screening campaign using a commercial compound library (ChemBridge DiverSET) revealed diverse chemotypes as inhibitors of the human dCTP pyrophosphatase 1 (dCTPase). Triazole, triazolopyrimidine, triazinoindole, quinoline hydrazone and arylpiperazine hits were clustered, confirmed by IC50 determinations, and their preliminary structure-activity-relationships (SAR) and ligand efficiency scores are discussed in this letter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Heterocyclic Compounds / chemical synthesis
  • Heterocyclic Compounds / chemistry
  • Heterocyclic Compounds / pharmacology*
  • Humans
  • Hydrazones / chemical synthesis
  • Hydrazones / chemistry
  • Hydrazones / pharmacology
  • Indoles / chemical synthesis
  • Indoles / chemistry
  • Indoles / pharmacology
  • Molecular Structure
  • Piperazines / chemical synthesis
  • Piperazines / chemistry
  • Piperazines / pharmacology
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology
  • Pyrophosphatases / antagonists & inhibitors*
  • Pyrophosphatases / metabolism
  • Quinolines / chemical synthesis
  • Quinolines / chemistry
  • Quinolines / pharmacology
  • Structure-Activity Relationship
  • Triazoles / chemical synthesis
  • Triazoles / chemistry
  • Triazoles / pharmacology

Substances

  • Enzyme Inhibitors
  • Heterocyclic Compounds
  • Hydrazones
  • Indoles
  • Piperazines
  • Pyrimidines
  • Quinolines
  • Triazoles
  • Pyrophosphatases
  • dCTP pyrophosphatase