Development of a series of novel o-phenylenediamine-based indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors

Bioorg Med Chem Lett. 2018 Feb 15;28(4):732-736. doi: 10.1016/j.bmcl.2018.01.010. Epub 2018 Jan 11.

Abstract

A novel series of o-phenylenediamine-based inhibitors of indoleamine 2,3-dioxygenase (IDO) has been identified. IDO is a heme-containing enzyme, overexpressed in the tumor microenvironment of many cancers, which can contribute to the suppression of the host immune system. Synthetic modifications to a previously described diarylether series resulted in an additional degree of molecular diversity which was exploited to afford compounds that demonstrated significant potency in the HeLa human cervical cancer IDO1 assay. .

Keywords: IDO; IDO1; Immuno-oncology; Indoleamine 2,3-dioxygenase; Kynurenine.

MeSH terms

  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacology*
  • HeLa Cells
  • Humans
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / antagonists & inhibitors*
  • Microsomes, Liver / metabolism
  • Phenylenediamines / chemical synthesis
  • Phenylenediamines / chemistry
  • Phenylenediamines / metabolism
  • Phenylenediamines / pharmacology*
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • IDO1 protein, human
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Phenylenediamines