198474-05-4Relevant articles and documents
Bf3-oet2 catalyzed c3-alkylation of indole: Synthesis of indolylsuccinimidesand their cytotoxicity studies
Shaikh, Iqbal N.,Rahim, Abdul,Faazil, Shaikh,Adil, Syed Farooq,Assal, Mohamed E.,Hatshan, Mohammad Rafe
, (2021/05/26)
A simple and efficient BF3-OEt2 promoted C3-alkylation of indole has been developed to obtain3-indolylsuccinimidesfrom commercially available indoles and maleimides, with excellent yields under mild reaction conditions. Furthermore,
Synthesis and biological evaluation of new multi-target 3-(1H-indol-3-yl)pyrrolidine-2,5-dione derivatives with potential antidepressant effect
Wróbel, Martyna Z.,Chodkowski, Andrzej,Herold, Franciszek,Marciniak, Monika,Dawidowski, Maciej,Siwek, Agata,Starowicz, Gabriela,Stachowicz, Katarzyna,Szewczyk, Bernadeta,Nowak, Gabriel,Belka, Mariusz,B?czek, Tomasz,Sata?a, Grzegorz,Bojarski, Andrzej J.,Tur?o, Jadwiga
, (2019/10/05)
A series of novel 3-(1H-indol-3-yl)pyrrolidine-2,5-dione derivatives were synthesised and evaluated for their 5-HT1A/D2/5-HT2A/5-HT6/5-HT7 receptor affinity and serotonin reuptake inhibition. Most of the evaluated compounds displayed high affinities for 5-HT1A receptors (e.g., 4c Ki = 2.3 nM, 4l Ki = 3.2 nM). The antidepressant activity of the selected compounds was screened in vivo using the forced swim test (FST). The results indicate that compound MW005 (agonist of the pre- and postsynaptic 5-HT1A receptor) exhibited promising affinities for the 5-HT1A/SERT/D2/5-HT6/5-HT7 receptors and showed an antidepressant-like activity in the FST model.
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
Crosignani, Stefano,Bingham, Patrick,Bottemanne, Pauline,Cannelle, Hélène,Cauwenberghs, Sandra,Cordonnier, Marie,Dalvie, Deepak,Deroose, Frederik,Feng, Jun Li,Gomes, Bruno,Greasley, Samantha,Kaiser, Stephen E.,Kraus, Manfred,Négrerie, 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
, p. 9617 - 9629 (2017/12/26)
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 oncology. Starting from HTS hit 5, IDO-1 inhibitor 6 (EOS200271/PF-06840003) has been developed. The structure-activity relationship around 6 is described and rationalized using the X-ray crystal structure of 6 bound to human IDO-1, which shows that 6, 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. Clinical candidate 6 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.
