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.
David K Williams  1 ,  Jay A Markwalder  2 ,  Aaron J Balog  2 ,  Bin Chen  2 ,  Libing Chen  2 ,  Jennifer Donnell  2 ,  Lauren Haque  2 ,  Amy C Hart  2 ,  Sunil K Mandal  3 ,  Andrew Nation  2 ,  Weifang Shan  2 ,  Gregory D Vite  2 ,  Kelly Covello  4 ,  John T Hunt  4 ,  Maria N Jure-Kunkel  5 ,  Steven P Seitz  2
Affiliations
  • 1. Oncology Chemistry, Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-5400, United States. Electronic address: [email protected].
  • 2. Oncology Chemistry, Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-5400, United States.
  • 3. Biocon BMS Research and Development Center (BBRC), Syngene International Ltd, Plat No. 2 & 3, Bommasandra IV Phase, Jigani Link Road, Bangalore 560 099, India.
  • 4. Oncology Biology, Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-5400, United States.
  • 5. MedImmune, One MedImmune Way, Gaithersburg, MD 020874, United States.
PMID: 29398543 DOI: 10.1016/j.bmcl.2018.01.010
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.
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