Identification of the First Highly Subtype-Selective Inhibitor of Human GABA Transporter GAT3 was written by Damgaard, Maria;Al-Khawaja, Anas;Vogensen, Stine B.;Jurik, Andreas;Sijm, Maarten;Lie, Maria E. K.;Baek, Mathias I.;Rosenthal, Emil;Jensen, Anders A.;Ecker, Gerhard F.;Froelund, Bente;Wellendorph, Petrine;Clausen, Rasmus P.. And the article was included in ACS Chemical Neuroscience in 2015.Electric Literature of C10H9NO2 The following contents are mentioned in the article:
Screening a library of small-mol. compounds using a cell line expressing human GABA transporter 3 (hGAT3) in a [3H]GABA uptake assay identified isatin derivatives as a new class of hGAT3 inhibitors. A subsequent structure-activity relationship (SAR) study led to the identification of hGAT3-selective inhibitors (i.e., compounds 20 and 34) that were superior to the reference hGAT3 inhibitor, (S)-SNAP-5114, in terms of potency (low micromolar IC50 values) and selectivity (>30-fold selective for hGAT3 over hGAT1/hGAT2/hBGT1). Further pharmacol. characterization of compound 20 (5-(thiophen-2-yl)indoline-2,3-dione) revealed a noncompetitive mode of inhibition at hGAT3. This suggests that this compound class, which has no structural resemblance to GABA, has a binding site different from the substrate, GABA. This was supported by a mol. modeling study that suggested a unique binding site that matched the observed selectivity, inhibition kinetics, and SAR of the compound series. These compounds are the most potent GAT3 inhibitors reported to date that provide selectivity for GAT3 over other GABA transporter subtypes. This study involved multiple reactions and reactants, such as 4,7-Dimethylindoline-2,3-dione (cas: 15540-90-6Electric Literature of C10H9NO2).
4,7-Dimethylindoline-2,3-dione (cas: 15540-90-6) belongs to indole derivatives. Indole exists overwhelmingly in the 1H-indole form as do other simple indoles. It is used in perfumery and in making tryptophan, an essential amino acid, and indoleacetic acid (heteroauxin), a hormone that promotes the development of roots in plant cuttings.Electric Literature of C10H9NO2
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Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles