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Structure of Indole-3-Glyoxylyl Chloride
CAS No.: 22980-09-2
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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Faisal Aziz ; Kanamata Reddy ; Virneliz Fernandez Vega ; Raja Dey ; Katherine A. Hicks ; Sumitha Rao , et al.
Abstract: The suppressor of T cell receptor signaling (Sts) proteins are negative regulators of immune signaling. Genetic inactivation of these proteins leads to significant resistance to infection. From a 590,000 compound high-throughput screen, we identified the 2-(1H)-quinolinone derivative, rebamipide, as a putative inhibitor of Sts phosphatase activity. Rebamipide, and a small library of derivatives, are competitive, selective inhibitors of Sts-1 with IC50 values from low to submicromolar. SAR analysis indicates that the quinolinone, the acid, and the amide moieties are all essential for activity. A crystal structure confirmed the SAR and reveals key interactions between this class of compound and the protein. Although rebamipide has poor cell permeability, we demonstrated that a liposomal preparation can inactivate the phosphatase activity of Sts-1 in cells. These studies demonstrate that Sts-1 enzyme activity can be pharmacologically inactivated and provide foundational tools and insights for the development of immune-enhancing therapies that target the Sts proteins.
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Purchased from AmBeed: 2251-65-2 ; 90098-04-7 ; 4876-14-6 ; 90098-08-1 ; 874-60-2 ; 4876-10-2 ; 7158-32-9 ; 5271-67-0 ; 118-45-6 ; 73-22-3 ; 56-41-7 ; 34893-92-0 ; 403-43-0 ; 58757-38-3 ; 76903-88-3 ; 52-90-4 ; 6068-72-0 ; 4122-68-3 ; 2243-83-6 ; 38818-50-7 ; 16331-45-6 ; 36823-88-8 ; 90098-06-9 ; 90098-05-8 ; 3024-72-4 ; 618-46-2 ; 63024-43-1 ; 22980-09-2 ; 681806-75-7 ; 39544-74-6
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CAS No. : | 22980-09-2 |
Formula : | C10H6ClNO2 |
M.W : | 207.61 |
SMILES Code : | O=C(Cl)C(C1=CNC2=C1C=CC=C2)=O |
MDL No. : | MFCD00015460 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H314 |
Precautionary Statements: | P280-P305+P351+P338-P310 |
Class: | 8 |
UN#: | 1759 |
Packing Group: | Ⅱ |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
2.5 g | In methanol; diethyl ether; at -78 - 20℃; | To a solution of indole (2.0 g, 17.1 mmol) in Et2O (20 mL) was added oxalyl chloride (1.5 mL, 17.2 mmol) dropwise at 0 C. The yellow slurry was stirred at same temperature for 0.5 h and then cooled to -78 C. A solution of NaOMe in MeOH (25 wt %, 7.8 mL, 34.1 mmol) was added to this slurry at same temperature. After addition, the reaction mixture was allowed to warm to ambient temperature, and quenched by addition of H2O (10 mL). The precipitate was collected by filtration, washed with H2O and dried to give 12 (2.5 g, 73%) as a yellow solid: mp 160 C (dec.); 1H NMR (DMSO-d6) δ 12.42 (s, 1H), 8.45 (d, J = 3.5 Hz, 1H), 8.16 (dd, J = 1.5, 6.0 Hz, 1H), 7.55 (dd, J = 1.5, 6.0 Hz, 1H), 7.32-7.27 (m, 2H), 3.89 (s, 3H). |
2.53 g | In methanol; diethyl ether; at -78 - 20℃; | To a stirred solution of indole (2.0 g, 17.1 mmol) in Et2O (20 mL) was added oxalyl chloride (1.5 mL,17.2 mmol) dropwise at 0 C. After the resultant yellow slurry was stirred at 0 C for 0.5 h, it was cooled to -78 C. A solution of NaOMe in MeOH (25 wt %, 7.8 mL, 34.1 mmol) was added to this slurry at -78 C. The reaction mixture was allowed to warm to room temperature and quenched by addition of water (10 mL). The solid was collected by filtration, rinsed with water and dried to give 4a (2.53 g, 73%) as a yellow solid |