504433-23-2

Basic information

• Product Name: GW441756
• Synonyms: 1,3-DIHYDRO-3-[(1-METHYL-1H-INDOL-3-YL)METHYLENE]-2H-PYRROLO[3,2-B]PYRIDIN-2-ONE;GW 441756;Gw;2H-Pyrrolo[3,2-b]pyridin-2-one, 1,3-dihydro-3-[(1-methyl-1H-indol-3-yl)methylene]-;(Z)-3-((1-methyl-1H-indol-3-yl)methylene)-1H-pyrrolo[3,2-b]pyridin-2(3H)-one;-3-((1-methyl-1H-indol-3-yl)methylene)-1H-pyrrolo[3,2-b]pyridin-2(3H)-one;3-[(1-methylindol-3-yl)methylidene]-1H-pyrrolo[3,2-b]pyridin-2-one
• CAS NO: 504433-23-2
• Molecular Formula: C17H13N3O
• Molecular Weight: 275.30462
• Product Categories: Angiogenesis and Metastasis;Inhibitors
• Mol File: 504433-23-2.mol

Chemical Properties

• Boiling Point: 567.985 °C at 760 mmHg
• Flash Point: 297.307 °C
• Appearance: /
• Density: 1.318 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.708
• Storage Temp.: Store at RT
• Solubility: Soluble in DMSO (up to 5 mg/ml).
• PKA: 11.04±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: GW441756(CAS DataBase Reference)
• NIST Chemistry Reference: GW441756(504433-23-2)
• EPA Substance Registry System: GW441756(504433-23-2)

Safety Data

• Hazardous Substances Data: 504433-23-2(Hazardous Substances Data)

Usage

Biological Activity

Potent, selective inhibitor of the NGF receptor tyrosine kinase A (TrkA) (IC 50 = 2 nM). Displays > 100-fold selectivity over a range of other kinases.

References

1) Wood et al. (2004) Discovery and in vitro evaluation of potent TrkA kinase inhibitors: oxindole and aza-oxindoles. Bioorg. Med. Chem. Lett. 14 953 2) Takemoto et al. (2015) Neuroprotection elicited by nerve growth factor and brain-derived neurotrophic factor released from astrocytes in response to methylmercury; Environ. Toxicol. Pharmacol. 40 199 [Focus Citation]

InChI:InChI=1/C17H13N3O/c1-20-10-11(12-5-2-3-7-15(12)20)9-13-16-14(19-17(13)21)6-4-8-18-16/h2-10H,1H3,(H,19,21)/b13-9-

Upstream product

• 19012-03-4 N-methyl-3-formylindole 
• 32501-05-6 1,3-dihydro-2H-pyrrolo[3,2-b]pyridin-2-one 
• 5470-18-8 2-Chloro-3-nitropyridine 
• 64362-41-0 diethyl 2-(3-nitropyridin-2-yl)malonate 
• 154078-83-8 ethyl 2-(3-nitro-pyridin-2-yl)-acetate 
• 295327-27-4 ethyl 2-(3-amino-pyridin-2-yl)-acetate 
• 1243657-75-1 diethyl 2-(2-bromopyridin-3-ylamino)-2-oxoethylphosphonate 

Relevant articles and documents

Tandem Horner-Wadsworth-Emmons/Heck procedures for the preparation of 3-alkenyl-oxindoles: The synthesis of Semaxanib and GW441756

A tandem sequence involving Horner-Wadsworth-Emmons (HWE) olefination followed by a palladium-catalysed intramolecular Heck reaction has been developed to provide rapid access to 3-alkenyl-oxindoles from α-halo-anilides. This one-pot microwave accelerated process proceeds with catalytic palladium(II) acetate or tetrakis(triphenylphosphine)palladium, and has been used to prepare a range of adducts derived from aromatic, heteroaromatic and aliphatic aldehydes. The procedures can be used to prepare N-unprotected oxindoles directly and the applicability of the process has been established by carrying out one-pot syntheses of Semaxanib, an angiogenesis signalling inhibitor, and GW441756, an aza-oxindole Trk A inhibitor.

Discovery and in vitro evaluation of potent TrkA kinase inhibitors: Oxindole and aza-oxindoles

The discovery, synthesis, potential binding mode, and in vitro kinase profile of 3-(3-bromo-4-hydroxy-5-(2′-methoxyphenyl)-benzylidene)-5-bromo- 1,3-dihydro-pyrrolo[2,3-b]pyridin-2-one, 3-[(1-methyl-1H-indol-3-yl)methylene]- 1,3-dihydro-2H-pyrrolo[3,2-b]-pyridin-2-one as potent TrkA inhibitors are discussed.