141595-98-4Relevant articles and documents
Indole-quinolizine-6-formyl-glucuronyl-ethylenediamine, preparation, activity and application thereof
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Paragraph 0020-0021, (2018/04/03)
The invention provides N-(6S)-3-acetyl base-4-oxo-4,6,7,12-tetraindole-[2,3-alpha]quinolizine-6-formyl-N'-glucuronyl-ethylenediamine, provides a preparation method thereof, discloses the anti-tumor activity thereof in a mice S180 transplanted sarcoma model, discloses the anti-tumor metastasis activity thereof in a mice Lewis lung cancer metastasis model, discloses an anti-inflammation role thereofin a mice ear swelling model, and further discloses an anti-thrombus role thereof in a rat common carotid artery-external jugular vein circulation bypath thread method anti-thrombus model. The invention discloses application of N-(6S)-3-acetyl base-4-oxo-4,6,7,12-tetraindole-[2,3-alpha]quinolizine-6-formyl-N'-glucuronyl-ethylenediamine in preparation of anti-tumor drugs, anti-lung cancer metastasis drugs, anti-inflammation drugs and anti-thrombus drugs.
Synthesis and evaluation of oxindoles as promising inhibitors of the immunosuppressive enzyme indoleamine 2,3-dioxygenase 1
Paul, Saurav,Roy, Ashalata,Deka, Suman Jyoti,Panda, Subhankar,Srivastava, Gopal Narayan,Trivedi, Vishal,Manna, Debasis
, p. 1640 - 1654 (2017/08/22)
Indoleamine 2,3-dioxygenase 1 (IDO1) is considered as an important therapeutic target for the treatment of cancer, chronic infections and other diseases that are associated with immune suppression. Recent developments in understanding the catalytic mechanism of the IDO1 enzyme revealed that conversion of l-tryptophan (l-Trp) to N-formylkynurenine proceeded through an epoxide intermediate state. Accordingly, we synthesized a series of 3-substituted oxindoles from l-Trp, tryptamine and isatin. Compounds with C3-substituted oxindole moieties showed moderate inhibitory activity against the purified human IDO1 enzyme. Their optimization led to the identification of potent compounds, 6, 22, 23 and 25 (IC50 = 0.19 to 0.62 μM), which are competitive inhibitors of IDO1 with respect to l-Trp. These potent compounds also showed IDO1 inhibition potencies in the low-micromolar range (IC50 = 0.33-0.49 μM) in MDA-MB-231 cells. The cytotoxicity of these potent compounds was trivial in different model cancer (MDA-MB-231, A549 and HeLa) cells and macrophage (J774A.1) cells. Stronger selectivity for the IDO1 enzyme (124 to 210-fold) over the tryptophan 2,3-dioxygenase (TDO) enzyme was also observed for these compounds. These results suggest that the oxindole moiety of the compounds could mimic the epoxide intermediate state of l-Trp. Therefore, the structural simplicity and low-micromolar inhibition potencies of these 3-substituted oxindoles make them quite attractive for further investigation of IDO1 function and immunotherapeutic applications.
A general and enantioselective approach to pentoses: A rapid synthesis of PSI-6130, the nucleoside core of sofosbuvir
Peifer, Manuel,Berger, Rapha?lle,Shurtleff, Valerie W.,Conrad, Jay C.,Macmillan, David W. C.
supporting information, p. 5900 - 5903 (2014/05/20)
An efficient route towards biologically relevant pentose derivatives is described. The de novo synthetic strategy features an enantioselective α-oxidation reaction enabled by a chiral amine in conjunction with copper(II) catalysis. A subsequent Mukaiyama aldol coupling allows for the incorporation of a wide array of modular two-carbon fragments. Lactone intermediates accessed via this route provide a useful platform for elaboration, as demonstrated by the preparation of a variety of C-nucleosides and fluorinated pentoses. Finally, this work has facilitated expedient syntheses of pharmaceutically active compounds currently in clinical use.
