| Identification | Back Directory | [Name]
ESI 09 | [CAS]
263707-16-0 | [Synonyms]
ESI09
ESI-09
ESI 09
(E)-2-(5-(tert-butyl)isoxazol-3-yl)-N-(3-chlorophenyl)-2-oxoacetohydrazonoyl cyanide
(E)-3-(5-tert-butylisoxazol-3-yl)-2-(2-(3-chlorophenyl)hydrazono)-3-oxopropanenitrile
alpha-[(3-Chlorophenyl)hydrazono]-5-(1,1-dimethylethyl)-beta-oxo-3-isoxazolepropanenitrile
α-[2-(3-Chlorophenyl)hydrazinylidene]-5-(1,1-dimethylethyl)-b-oxo-3-isoxazolepropanenitrile
α-[(2-(3-Chlorophenyl)hydrazinylidene]-5-(1,1-dimethylethyl)-β-oxo-3-isoxazolepropanenitrile
3-Isoxazolepropanenitrile, α-[2-(3-chlorophenyl)hydrazinylidene]-5-(1,1-dimethylethyl)-β-oxo-
3-?Isoxazolepropanenitr?ile, α-?[2-?(3-?chlorophenyl)?hydrazinylidene]?-?5-?(1,?1-?dimethylethyl)?-?β-?oxo- | [Molecular Formula]
C16H15ClN4O2 | [MDL Number]
MFCD00109218 | [MOL File]
263707-16-0.mol | [Molecular Weight]
330.77 |
| Chemical Properties | Back Directory | [Melting point ]
>175°C (dec.) | [storage temp. ]
2-8°C | [solubility ]
DMSO: soluble20mg/mL, clear | [form ]
powder | [color ]
, faint yellow to dark orange | [InChI]
InChI=1S/C16H15ClN4O2/c1-16(2,3)14-8-12(21-23-14)15(22)13(9-18)20-19-11-6-4-5-10(17)7-11/h4-8,19H,1-3H3/b20-13+ | [InChIKey]
DXEATJQGQHDURZ-DEDYPNTBSA-N | [SMILES]
C(/C#N)(=N/NC1=CC=CC(Cl)=C1)\C(C1C=C(C(C)(C)C)ON=1)=O |
| Hazard Information | Back Directory | [Uses]
ESI 09 acts as an EPAC inhibitor, preventing EPAC-mediated insulin release form β-pancreatic cells. Selective control for EPAC over PKA and decreases migration and invasion of AsPc-1 and PANC-1 pancreatic cancer cells. | [Biochem/physiol Actions]
ESI-09 is a potent, specific inhibitor of EPAC (exchange protein directly activated by cAMP). ESI-09 inhibits EPAC1 and EPAC2 with IC50 values of 3.2 and 1.4 μM, respectively, with no activity against PKA at 25 μM. In pancreatic cell lines, the compound blocks phosphorylation of Akt and insulin secretion. ESI-09 inhibits migration of pancreatic cancer cell lines. | [Synthesis]
1. 3-Chloroaniline (30 mg, 0.24 mmol) was dissolved in 1 mL of cooled solvent at -5°C.
2. 0.24mL of 1N HCl (aq.) was added to the above solution to form an acidic aniline solution.
3. 1 mL of an aqueous solution of sodium nitrite (16 mg, 0.24 mmol) was added slowly and dropwise to the acidic aniline solution to form an aryl diazonium salt solution.
4. Sodium acetate (33 mg, 0.4 mmol) was added to the aryl diazonium salt solution, followed by the addition of 1 mL of crude 3-(5-tert-butylisoxazol-3-yl)-3-oxopropanenitrile (38 mg, 0.2 mmol) in ethanol.
5. The reaction mixture was stirred at 0 °C for 5 min, then poured into 10 mL of water and extracted with ethyl acetate (20 mL).
6. The organic layer was dried with anhydrous Na2SO4, filtered and concentrated under reduced pressure.
7. The residue was purified by silica gel short column chromatography using hexane/ethyl acetate (2:1) as eluent to afford the target product 2-(5-(tert-butyl)isoxazol-3-yl)-N-(3-chlorophenyl)-2-oxoethylidenehydrazonium cyanide (40 mg, 61% yield) as a yellow solid with a melting point of 146-147 °C. The product was analyzed by HPLC.
8. HPLC analysis showed the product to be 99.6% pure (retention time fR = 21.72 min).
9. The structure of the product was confirmed by 1H NMR, 13C NMR and HRMS (ESI). | [in vivo]
Treatment with ESI-09 dramatically protects WT mice against R. australisinfection with much milder disease manifestations and significantly improves survival[2]. | [storage]
Store at -20°C | [References]
[1] Tetrahedron Letters, 2013, vol. 54, # 12, p. 1546 - 1549
[2] Patent: WO2013/119931, 2013, A1. Location in patent: Paragraph 0214 |
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