5812-07-7

Basic information

• Product Name: SU 4312
• Synonyms: 3-[[(4-DIMETHYLAMINO)PHENYL]METHYLENE]-1,3-DIHYDRO-2H-INDOL-2-ONE;3-(4-DIMETHYLAMINOBENZYLIDENYL)-2-INDOLINONE;2H-Indol-2-one, 3-[[4-(dimethylamino)phenyl]methylene]-1,3-dihydro;3-[[(4-Dimethylamino)phenyl]methylene]-1,3-dihydro-2H-indol-2-one, E/Z mixture;NSC 86429;SU 4312
• CAS NO: 5812-07-7
• Molecular Formula: C17H16N2O
• Molecular Weight: 264.32
• Product Categories: Protein Kinase;Angiogenesis and Metastasis
• Mol File: 5812-07-7.mol

Chemical Properties

• Melting Point: 225-232 °C
• Boiling Point: 497.1°C at 760 mmHg
• Flash Point: 254.5°C
• Appearance: orange/
• Density: 1.219g/cm³
• Vapor Pressure: 5.09E-10mmHg at 25°C
• Refractive Index: 1.683
• Storage Temp.: 2-8°C
• Solubility: DMSO: 30 mg/mL
• PKA: 12.89±0.20(Predicted)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.
• CAS DataBase Reference: SU 4312(CAS DataBase Reference)
• NIST Chemistry Reference: SU 4312(5812-07-7)
• EPA Substance Registry System: SU 4312(5812-07-7)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• WGK Germany: 3
• Hazardous Substances Data: 5812-07-7(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
SU 4312 is used as a vascular endothelial growth factor receptor KDR tyrosine kinase antagonist for the treatment of various types of cancer. It plays a crucial role in inhibiting the VEGF receptor protein tyrosine kinase 1/2 and PDGF receptor, which are essential for angiogenesis and tumor growth. By targeting these receptors, SU 4312 can potentially limit the growth and spread of cancer cells.
Used in Neuroprotection:
SU 4312 is used as a neuroprotective agent against NO-mediated neurotoxicity. Its ability to inhibit neuronal nitric oxide synthase (NOS) makes it a promising candidate for the treatment of neurological disorders associated with nitric oxide-induced damage.

Biological Activity

Potent and selective inhibitor of VEGFR and PDGFR tyrosine kinases (IC 50 values are 0.8 and 19.4 mM respectively). Selective over EGFR and c-Src tyrosine kinases.

References

1) Kendall et al. (1999), Vascular endothelial growth factor receptor KDR tyrosine kinase activity is increased by autophosphorylation of two activation loop tyrosine residues; J. Biol. Chem., 274 6453 2) Sun et al. (1998), Synthesis and biological evaluations of 3-substituted indolin-2-ones: a novel class of tyrosine kinase inhibitors that exhibit selectivity toward particular receptor tyrosine kinases; J. Med. Chem., 41 2588

InChI:InChI=1/C17H16N2O/c1-19(2)13-9-7-12(8-10-13)11-15-14-5-3-4-6-16(14)18-17(15)20/h3-11H,1-2H3,(H,18,20)/b15-11+

Upstream product

• 59-48-3 2-oxoindole 
• 100-10-7 4-dimethylamino-benzaldehyde 
• 90828-16-3 (Z)-3-(4-(dimethylamino)benzylidene)indolin-2-one 
• 91-56-5 indole-2,3-dione 

Relevant articles and documents

Pharmacophore based drug design and synthesis of oxindole bearing hybrid as anticancer agents

Dual TK inhibitors have shown significant clinical effects against many tumors, but with unmanageable side effects. Design approach and selectivity of these inhibitors plays substantial role in their potency and side-effects. Understanding the homology of binding sites in targeted receptors, and involvement of signaling proteins after the inhibition might help in producing less toxic but effective inhibitors. Herein, we designed benzylideneindolon-2-one derivatives based on homology modeling in binding sites of VEGFR-2 and EGFR receptors as dual- inhibitor potent anticancer compounds with high selectivity. The benzylideneindolon-2-one derivatives were found to possess conformational switch in form of oxindole, substituted at 2-benzimidazole. Within synthesized compounds, 5b was found most active in in-vitro enzyme inhibition assay against VEGFR-2 and EGFR with highest IC50 value of 6.81 ± 2.55 and 13.04 ± 4.07 nM, respectively. Interestingly, cytotoxicity studies revealed selective toxicity of compound 5b against proliferation of A-431 cell lines (over expressed VEGFR-2 and EGFR) with GI50 value of 0.9 ± 0.66 μM. However, the compounds showed mild to moderate activity in all other cancer cell line in the range of 0.2–100 μM. Further mode of action studies by flow cytometry and western blot on A-431 indicated that they work via apoptosis at S- phase following Bcl/Bax pathway, and cell migration via MMP9. 5b not only suppressed tumor growth but also improved vandetanib associated with weight loss toxicity. Moreover, 5b was found safer than sunitinib and erlotinib with LD50 of 500 mg/kg body weight. These results propose 5b as potential anti-tumor drug with safer profile of conventional inhibitors of VEGFR-2 and EGFR for solid tumors.

3-aryl-indolinones derivatives as antiplasmodial agents: synthesis, biological activity and computational analysis

Malaria is an infectious illness, affecting vulnerable populations in Third World countries. Inspired by natural products, indole alkaloids have been used as a nucleus to design new antimalarial drugs. So, eighteen oxindole derivatives, aza analogues were obtained with moderate to excellent yields. Also, the saturated derivatives of oxindole and aza derivatives via H2/Pd/C reduction were obtained in good yields, leading to racemic mixtures of each compound. Next, the inhibitory activity against P. falciparum of 18 compounds were tested, founding six compounds with IC50 20 μM. The most active of these compounds was 8c; however, their unsaturated derivative 7c was inactive. Then, a structure-activity relationship analysis was done, founding that focused LUMO lobe on the specific molecular zone is related to inhibitory activity against P. falciparum. Finally, we found a potential inhibition of lactate dehydrogenase by oxindole derivatives, using molecular docking virtual screening.

Selective C3-alkenylation of oxindole with aldehydes using heterogeneous CeO2 catalyst

We report herein that a commercially available CeO2 is an active and reusable catalyst for the C3-selective alkenylation of oxindole with aldehydes under solvent-free conditions. This catalytic method is generally applicable to different aromatic and aliphatic aldehydes, giving 3-alkyledene-oxindoles in high yields (87%–99%) and high stereoselectivities (79%–93% to E-isomers). This is the first example of the catalytic synthesis of 3-alkenyl-oxindoles from oxindole and various aliphatic aldehydes. The Lewis acid-base interaction between Lewis acid sites on CeO2 and benzaldehyde was studied by in situ IR. The structure-activity relationship study using CeO2 catalysts with different sizes suggests that defect-free CeO2 surface is the active site for this reaction.

Design, synthesis and biological evaluation of oxindole-based chalcones as small-molecule inhibitors of melanogenic tyrosinase

The enzyme tyrosinase regulates melanogenesis and skin hyperpigmentation by converting L-3,4-dihy-droxyphenylalanine (L-DOPA) into dopaquinone, a key step in the melanin biosynthesis. The present work deals with design and synthesis of various oxindole-ba

Investigation of triazole-linked indole and oxindole glycoconjugates as potential anticancer agents: Novel Akt/PKB signaling pathway inhibitors

In continuation of our venture towards the synthesis of novel bioactive agents, two sets of triazole-linked glycoconjugates were synthesized from indole/oxindole (29 compounds) and were further characterized by IR (infrared spectroscopy), 1H NM

Design, Synthesis, and Characterization of 3-(Benzylidene)indolin-2-one Derivatives as Ligands for α-Synuclein Fibrils

A series of 3-(benzylidine)indolin-2-one derivatives were synthesized and evaluated for their in vitro binding to alpha synuclein (α-syn), beta amyloid (Aβ), and tau fibrils. Compounds with a single double bond in the 3-position had only a modest affinity

METHOD OF USING AN INDOLINONE MOLECULE AND DERIVATIVES FOR INHIBITING LIVER FIBROSIS AND HEPATITIS

This invention relates to methods of reversing and inhibiting liver fibrosis and hepatitis using a small indolinone molecule Hesperadin and related compounds. Methods of identifying such agents and using them to inhibit the expression of collagens and ECM

Synthesis and anti-tyrosine kinase activity of 3-(substituted-benzylidene)- 1, 3-dihydro-indolin derivatives: Investigation of their role against p60 c-Src receptor tyrosine kinase with the application of receptor docking studies

A series of 3-(substituted-benzylidene)-1, 3-dihydro-indolin-2-thione derivatives were synthesized as modified congeners of 3-(substituted- benzylidene)-1, 3-dihydro-indolin-2-one series. All the synthesized compounds were examined for their in vitro anti-tyrosine kinase activity against p60 c-Src. The activity results revealed that compounds (Z)-3-(4′-Dimethylamino-benzylidene)-1, 3-dihydro-indolin-2-thione (12) (E)-3-(2′, 6′-Dichloro-benzylidene)-1, 3-dihydro-indolin-2-thione (13) and (E)-3-(3′-Hydroxy-4′-methoxy-benzylidene)-1, 3-dihydro-indolin-2-thione (19) exhibited anti-tyrosine kinase activity with IC50 value of 21.91, 21.20 and 30.92 μM, respectively. These results are comparable to PP1 [1-tert-Butyl-3-p-tolyl-1H-pyrazolo[3, 4-d]pyrimidine-4-yl-amine] (IC50 = 0.17 μM), which is reported as a potent and selective p60c-Src tyrosine kinase inhibitor. Some thio congeners are found to be more potent than oxo derivatives; however, no significant correlation was observed between the activity profiles of these two series. Docking program was used to investigate the docking mode of each compound at the active site. Among all of the compounds, only (Z)-3-(2′-Chloro-benzylidene)-1, 3-dihydro-indolin-2-one (8) and (E)-3-(3′-Nitro-benzylidene)-1, 3-dihydro-indolin-2-thione (16) were docked at the active site where the PP1 was embedded.

Synthesis and biological evaluations of 3-substituted indolin-2-ones: A novel class of tyrosine kinase inhibitors that exhibit selectivity toward particular receptor tyrosine kinases

3-Substituted indolin-2-ones have been designed and synthesized as a novel class of tyrosine kinase inhibitors which exhibit selectivity toward different receptor tyrosine kinases (RTKs). These compounds have been evaluated for their relative inhibitory properties against a panel of RTKs in intact cells. By modifying the 3-substituted indolin-2-ones, we have identified compounds which showed selective inhibition of the ligand- dependent autophosphorylation of various RTKs at submicromolar levels in cells. Structure-activity analysis for these compounds and their relative potency and selectivity to inhibit particular RTKs has determined that (1) 3- [(five-membered heteroaryl ring)methylidenyl]indolin-2-ones are highly specific against the VEGF (Flk-1) RTK activity, (2) 3-(substituted benzylidenyl)indolin-2-ones containing bulky group(s) in the phenyl ring at the C-3 position of indolin-2-ones showed high selectivity toward the EGF and Her-2 RTKs, and (3) the compound containing an extended side chain at the C- 3 position of the indolin-2-one (16) exhibited high potency and selectivity when tested against the PDGF and VEGF (Flk-1) RTKs. Recent published crystallographic data for two of these 3-substituted indolin-2-ones provides a rationale to suggest that these compounds may bind in the ATP binding pocket of RTKs. The structure-activity analysis supports the use of subsets of these compounds as specific chemical leads for the development of RTK- specific drugs with broad application for the treatment of human diseases.

(Z)- AND (E)-ARYLIDENE-1,3-DIHYDROINDOL-2-ONES : CONFIGURATION, CONFORMATION, AND INFRARED CARBONYL STRETCHING FREQUENCIES

The configuration and conformation of both (Z)- and (E)-arylidene-1,3-dihydroindol-2-ones were investigated.In the solid state the Z-isomer is planar whereas the E-isomer has the aryl group significantly twisted, as shown by two X-ray structures.A linear