190326-02-4

Upstream product

• 541-59-3 maleiimide 
• 1006-94-6 5-methoxylindole 

Relevant academic research and scientific papers

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

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.

Bf3-oet2 catalyzed c3-alkylation of indole: Synthesis of indolylsuccinimidesand their cytotoxicity studies

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

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.

PYRROLIDINE-2, 5-DIONE DERIVATIVES, PHARMACEUTICAL COMPOSITIONS AND METHODS FOR USE AS IDO1 INHIBITORS

The present invention relates to compound of Formula I or pharmaceutically acceptable enantiomers, salts, solvates or prodrugs thereof. The invention further relates to the use of the compounds of Formula I as IDO1 inhibitors. The invention also relates to the use of the compounds of Formula I for the treatment and/or prevention of cancer and endometriosis. The invention also relates to a process for manufacturing compounds of Formula I.

Highly efficient aluminum trichloride catalyzed michael addition of indoles and pyrroles to maleimides

A highly efficient synthetic strategy for Michael addition of indoles and pyrroles to maleimides has been developed using the Lewis acids zinc chloride or aluminum trichloride as the catalyst. The reactions generated 3-substituted indoles and 2-substitute

Expedited synthesis of substituted dipyrrolo[3,4-a:3,4-c]carbazole-1,3,4,6- tetraones structurally related to granulatimide

Dipyrrolo[3,4-a:3,4-c]carbazole-1,3,4,6-tetraones can be considered as granulatimide analogues. In view of structure-activity relationship studies in these series, a parallel liquid-phase microwave-assisted synthesis was developed to generate a small library of compounds bearing various substituents at positions 8, 9, 10, or 11 on the aromatic framework. Georg Thieme Verlag Stuttgart.

A direct synthesis of 3-(pyrrolidin-3-yl)indoles for use as conformationally restricted analogs of tryptamines

An efficient, two step synthesis of-(pyrrolidin-3-yl)indoles 4 is described. Indoles react with maleimides in refluxing acetic acid affording 3-(indol-3-yl)succinimides 6. Reaction times and yields depend on the substituents on the indole 5. Direct reduct