Discovery of a Novel and Selective Indoleamine 2,3-Dioxygenase (IDO-1) Inhibitor 3-(5-Fluoro-1H-indol-3-yl)pyrrolidine-2,5-dione (EOS200271/PF-06840003) and Its Characterization as a Potential Clinical Candidate was written by Crosignani, Stefano;Bingham, Patrick;Bottemanne, Pauline;Cannelle, Helene;Cauwenberghs, Sandra;Cordonnier, Marie;Dalvie, Deepak;Deroose, Frederik;Feng, Jun Li;Gomes, Bruno;Greasley, Samantha;Kaiser, Stephen E.;Kraus, Manfred;Negrerie, Michel;Maegley, Karen;Miller, Nichol;Murray, Brion W.;Schneider, Manfred;Soloweij, James;Stewart, Albert E.;Tumang, Joseph;Torti, Vince R.;Van Den Eynde, Benoit;Wythes, Martin. And the article was included in Journal of Medicinal Chemistry in 2017.SDS of cas: 1000343-16-7 The following contents are mentioned in the article:
Tumors use tryptophan-catabolizing enzymes such as indoleamine 2,3-dioxygenase (IDO-1) to induce an immunosuppressive environment. IDO-1 is induced in response to inflammatory stimuli and promotes immune tolerance through effector T-cell anergy and enhanced Treg function. As such, IDO-1 is a nexus for the induction of a key immunosuppressive mechanism and represents an important immunotherapeutic target in oncol. Starting from HTS hit I, IDO-1 inhibitor II has been developed. The structure-activity relationship around II is described and rationalized using the x-ray crystal structure of II bound to human IDO-1, which shows that II, differently from most of the IDO-1 inhibitors described so far, does not bind to the heme iron atom and has a novel binding mode. Clin. candidate II shows good potency in an IDO-1 human whole blood assay and also shows a very favorable ADME profile leading to favorable predicted human pharmacokinetic properties, including a predicted half-life of 16-19 h. This study involved multiple reactions and reactants, such as 5-Fluoro-6-methyl-1H-indole (cas: 1000343-16-7SDS of cas: 1000343-16-7).
5-Fluoro-6-methyl-1H-indole (cas: 1000343-16-7) belongs to indole derivatives. The indole subunit is an almost ubiquitous component of biologically active natural products, and its study has been the focus of research for decades. Indole plays a fundamental role for QS in E. coli, being one of the signal molecules responsible for the transcription of a variety of genes (gabT, and tnaB ASTD). SDS of cas: 1000343-16-7
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Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles