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Chemical Structure| 50995-74-9 Chemical Structure| 50995-74-9
Chemical Structure| 50995-74-9

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7ACC1 selectively interfere with lactate fluxes in the lactate-rich tumor microenvironment and inhibits lactate influx but not efflux in tumor cells expressing MCT1 and MCT4 transporters.

Synonyms: DEAC; Coumarin D 1421; 7-Diethylamino-2-oxo-2H-chromen-3-carboxylic Acid

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Product Citations

Haroon, Muhammad ; Sultana, Sharmin ; Najibi, Seyedeh A ; Wang, Emily T ; Michaelson, Abbey ; Al Muied, Pranto SM , et al.

Abstract: The imidazoquinoline family of toll-like receptor (TLR) immune cell agonists has long demonstrated moderate anticancer immunogenic effects by activating tumoricidal immune cells and depleting immunosuppressive cells within the tumor microenvironment. At a molecular level, we have also established that several imidazoquinolines traffic from within cancer cells to the extracellular space via P-glycoprotein (P-gp)-mediated efflux, a process commonly upregulated as multidrug-resistant (MDR) cancers acquire chemoresistance. However, imidazoquinoline P-gp efflux has never been deliberately enhanced to exploit this process. This study pioneers efforts to optimize imidazoquinoline efflux, ultimately balancing immunogenic potency alongside functional efflux susceptibility. Starting from an established imidazoquinoline scaffold previously optimized for potency, efflux was significantly enhanced by elaborating the N1 benzylic position with amide- and sulfonamide-linked P-gp affinity fragments consisting of empirically established P-gp substrates as well as computationally predicted P-gp binders. Lead compounds were identified from this series that exhibited enhanced P-gp efflux with functional retention of TLR agonism. Similar to the parent imidazoquinoline scaffold, leads had limited direct cytotoxicity in both treatment-naive and MDR B16 melanoma models and did not significantly affect the efficacy or trafficking of the chemotherapeutic doxorubicin. Efflux-enhanced imidazoquinolines were preferentially expelled from MDR-B16 cells relative to treatment-naive cells, resulting in immunogenicity that was enhanced as a consequence of the acquired MDR phenotype. Because enhanced P-gp-mediated efflux is common to most MDR cancer types, we envision that these results could inspire the design of immunotherapeutic drugs with mechanisms of action that are broadly enhanced in MDR cancers that have failed treatment or acquired resistance to chemotherapeutics.

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Product Details of 7ACC1

CAS No. :50995-74-9
Formula : C14H15NO4
M.W : 261.27
SMILES Code : O=C(C(C1=O)=CC2=C(O1)C=C(N(CC)CC)C=C2)O
Synonyms :
DEAC; Coumarin D 1421; 7-Diethylamino-2-oxo-2H-chromen-3-carboxylic Acid
MDL No. :MFCD00068721
InChI Key :WHCPTFFIERCDSB-UHFFFAOYSA-N
Pubchem ID :659294

Safety of 7ACC1

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Application In Synthesis of 7ACC1

* 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.

  • Downstream synthetic route of [ 50995-74-9 ]

[ 50995-74-9 ] Synthesis Path-Downstream   1~7

  • 1
  • [ 3337-66-4 ]
  • [ 50995-74-9 ]
  • C22H19I2NO6 [ No CAS ]
  • 2
  • [ 3337-66-4 ]
  • [ 50995-74-9 ]
  • C36H27N3O6 [ No CAS ]
  • 3
  • [ 138907-68-3 ]
  • [ 50995-74-9 ]
  • ethyl 5-(7-(diethylamino)-2-oxo-2H-chromene-3-carboxamido)-1-(4-fluorophenyl)-1H-pyrazole-4-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
67% With pyridine; trichlorophosphate; General procedure: Intermediate 4 (0.001mol) and 5 (0.001mol) were dissolved in pyridine, phosphorus oxychloride is slowly added dropwise under ice bath conditions, then at 40-60C reacted for 5-8h. Finally, the mixture was poured into 30mL saturated Na2CO3 solution and stirred well. After the mixture was acidified, the saturated CuSO4 solution was used to remove pyridine, which greatly improved the purity and yield of the product. The data for compounds 8I-8VI are provided in the supporting information.
  • 4
  • [ 50995-74-9 ]
  • [ 15001-11-3 ]
  • ethyl 5-(7-(diethylamino)-2-oxo-2H-chromene-3-carboxamido)-1-(p-tolyl)-1H-pyrazole-4-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
85% With pyridine; trichlorophosphate; General procedure: Intermediate 4 (0.001mol) and 5 (0.001mol) were dissolved in pyridine, phosphorus oxychloride is slowly added dropwise under ice bath conditions, then at 40-60C reacted for 5-8h. Finally, the mixture was poured into 30mL saturated Na2CO3 solution and stirred well. After the mixture was acidified, the saturated CuSO4 solution was used to remove pyridine, which greatly improved the purity and yield of the product. The data for compounds 8I-8VI are provided in the supporting information.
  • 5
  • [ 50995-74-9 ]
  • [ 51516-70-2 ]
  • N-(4-cyano-1-(4-fluorophenyl)-1H-pyrazol-5-yl)-7-(diethylamino)-2-oxo-2H-chromene-3-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
70% With pyridine; trichlorophosphate; General procedure: Intermediate 4 (0.001mol) and 5 (0.001mol) were dissolved in pyridine, phosphorus oxychloride is slowly added dropwise under ice bath conditions, then at 40-60C reacted for 5-8h. Finally, the mixture was poured into 30mL saturated Na2CO3 solution and stirred well. After the mixture was acidified, the saturated CuSO4 solution was used to remove pyridine, which greatly improved the purity and yield of the product. The data for compounds 8I-8VI are provided in the supporting information.
  • 6
  • [ 103646-82-8 ]
  • [ 50995-74-9 ]
  • N-(4-cyano-1-(p-tolyl)-1H-pyrazol-5-yl)-7-(diethylamino)-2-oxo-2H-chromene-3-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
70% With pyridine; trichlorophosphate; General procedure: Intermediate 4 (0.001mol) and 5 (0.001mol) were dissolved in pyridine, phosphorus oxychloride is slowly added dropwise under ice bath conditions, then at 40?60°C reacted for 5?8h. Finally, the mixture was poured into 30mL saturated Na2CO3 solution and stirred well. After the mixture was acidified, the saturated CuSO4 solution was used to remove pyridine, which greatly improved the purity and yield of the product. The data for compounds 8I-8VI are provided in the supporting information.
  • 7
  • [ 29390-67-8 ]
  • [ 50995-74-9 ]
  • 6-deoxy-6-amino-[3-{7-(diethylamino)coumarine}carboyl]-β-cyclodextrin [ No CAS ]
YieldReaction ConditionsOperation in experiment
3.9% A dimethylformamide solution of 7-(diethylamino)coumarine-3-carboxylic acid (70 mg, 0.27 mmol), dicyclohexylcarbodiimide(110 mg, 0.53 mmol), and 1-hydroxybenzotriazole(72 mg, 0.53 mmol) was stirred at 0 °C for30 min. To the mixture was added 6-deoxy-6-amino-beta-CD(250 mg, 0.22 mmol). The resulting solution was stirredat 0 °C for 5 h and subsequently at room temperature for 3days. After removing insoluble materials by filtration, thefiltrate was concentrated, and poured into acetone (500 mL)to form precipitates. The precipitate containing the productwas purified by column chromatography on high porouspolystylene gel, DIAION HP-20. The eluent with a 30percent methanol aqueous solution was concentrated to give thedesired product as a pale yellow solid (12 mg 3.9percent). Thepurity of the product was checked with TLC, 1H NMR, andelemental analysis.
 

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