Synfacts 2020; 16(04): 0371
DOI: 10.1055/s-0040-1707632
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart · New York

Synthesis of an Indoleamine-2,3-dioxygenase-1 (IDO1) Inhibitor

Philip Kocienski
Steeneck C. * Kinzel O, Anderhub S, Hornberger M, Pinto S, Morschhaeuser B, Braun F, Kleymann G, Hoffmann T. Phenex Pharmaceuticals AG, Heidelberg, Germany
Discovery of Hydroxyamidine Based Inhibitors of IDO1 for Cancer Immunotherapy with Reduced Potential for Glucuronidation.

ACS Med. Chem. Lett. 2020;
11: 179-187
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18. März 2020 (online)



Indoleamine-2,3-dioxygenase-1 (IDO1) is strongly involved in tumor immune resistance. The immune suppressive effect of IDO1 results from its capacity to degrade tryptophan to N-formylkyurenine, the first and rate-limiting step of the kyurenine pathway. The target molecule N is a low-nanomolar IDO1 inhibitor.



Reaction of aldoxime F with N-chlorosuccinimide (NCS) afforded N-hydroxycarbimidoyl chloride G. Treatment of G with 3-chloroaniline followed by hydroxyamidine cyclization using 1,1′-carbonyldiimidazole (CDI) and Boc deprotection afforded the key amino intermediate K.