SAR towards indoline and 3-azaindoline classes of IDO1 inhibitors

Bioorg Med Chem Lett. 2021 Sep 1:47:128214. doi: 10.1016/j.bmcl.2021.128214. Epub 2021 Jun 21.

Abstract

A novel series of IDO1 inhibitors have been identified with good IDO1 Hela cell and human whole blood activity. These inhibitors contain an indoline or a 3-azaindoline scaffold. Their structure-activity-relationship studies have been explored. Compounds 37 and 41 stood out as leads due to their good potency in IDO1 Hela assay, good IDO1 unbound hWB IC50s, reasonable unbound clearance, and good MRT in rat and dog PK studies.

Keywords: Antitumor; Azaindoline; Heme displacer; IDO1 inhibitor; Indoline.

MeSH terms

  • Animals
  • Aza Compounds / chemical synthesis
  • Aza Compounds / chemistry
  • Aza Compounds / pharmacology*
  • Dogs
  • Dose-Response Relationship, Drug
  • Humans
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / antagonists & inhibitors*
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
  • Indoles / chemical synthesis
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Male
  • Molecular Structure
  • Rats
  • Rats, Wistar
  • Structure-Activity Relationship

Substances

  • Aza Compounds
  • IDO1 protein, human
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Indoles
  • indoline