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

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

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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