Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000131.xml
Synfacts 2020; 16(04): 0371
DOI: 10.1055/s-0040-1707632
DOI: 10.1055/s-0040-1707632
Synthesis of Natural Products and Potential Drugs
Synthesis of an Indoleamine-2,3-dioxygenase-1 (IDO1) Inhibitor
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
Discovery of Hydroxyamidine Based Inhibitors of IDO1 for Cancer Immunotherapy with Reduced Potential for Glucuronidation.
ACS Med. Chem. Lett. 2020;
11: 179-187
Further Information
Publication History
Publication Date:
18 March 2020 (online)
Significance
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.
#
Comment
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.
#
#