AG 18

Chemical Properties

Yellow Powder

Uses

A specific inhibitor for the epidermal growth factor receptor. Also inhibits EGF-dependent cell proliferation (IC50=35uM).

Uses

AG 18 inhibits EGFR with IC50 of 35 μM.

Definition

ChEBI: 2-[(3,4-dihydroxyphenyl)methylidene]propanedinitrile is a member of catechols.

Biological Activity

Inhibitor of epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor (PDGFR) kinase (IC 50 values are 35 and 25 μ M respectively). Inhibits EGF-stimulated cell proliferation. Also acts as a mitochondrial uncoupler that alters phosphorylation-dependent cell signaling.

Biochem/physiol Actions

Tyrphostin 23 is a small molecule inhibitor of epidermal growth factor (EGF) receptor kinase function. This molecule associates with the substrate subsite of the protein tyrosine kinase (PTK) domain,.

Synthesis

Example 12 Preparation of 2-(3,4-dihydroxybenzylidene)malononitrile: A mixture of 3,4-bis(methoxymethoxy)benzaldehyde (1.0 mmol), malononitrile (1.0 mmol), and NaOH (2 mg) in 5 mL of methanol was stirred for 24 hours at room temperature. After completion of the reaction, the solvent was removed by distillation under reduced pressure, the residue was dissolved in ethyl acetate and filtered through a silica gel pad. The filtrate was concentrated under reduced pressure to give the condensation product 2-(3,4-bis(methoxymethoxy)benzylidene)malononitrile as a yellow solid in 94% yield. The structure of the product was confirmed by 1H-NMR (300 MHz, CDCl3) and 13C-NMR (75 MHz, CDCl3): 1H-NMR δ (ppm) 7.86 (s, 1H), 7.68 (s, 1H), 7.53 (d, J = 9 Hz, 1H), 7.29 (d, J = 9 Hz, 1H), 5.35 (s, 2H), 5.28 (s, 2H), 5.28 (s, 2H). 5.28 (s, 2H), 3.54 (s, 3H), 3.53 (s, 3H); 13C-NMR δ (ppm) 168.1, 167.6, 149.8, 147.9, 134.6, 127.7, 126.1, 121.0, 118.8, 116.8, 96.0, 95.5, 56.9, 56.8.

References

[1] Patent: US2003/73712, 2003, A1