(2R)-1-({4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl}oxy)propan-2-yl (2S)-2-aminopropanoate

• ChemBase ID: 72535
• Molecular Formular: C22H24FN5O4
• Molecular Mass: 441.4554632
• Monoisotopic Mass: 441.18123249
• SMILES: c12c(c(c(cc1)Oc1ncnn3c1c(c(c3)OC[C@@H](C)OC(=O)[C@@H](N)C)C)F)cc([nH]2)C
• Canonical SMILES: C[C@@H](OC(=O)[C@@H](N)C)COc1cn2c(c1C)c(ncn2)Oc1ccc2c(c1F)cc([nH]2)C
• InChI: InChI=1S/C22H24FN5O4/c1-11-7-15-16(27-11)5-6-17(19(15)23)32-21-20-13(3)18(8-28(20)26-10-25-21)30-9-12(2)31-22(29)14(4)24/h5-8,10,12,14,27H,9,24H2,1-4H3/t12-,14+/m1/s1
• InChIKey: LTEJRLHKIYCEOX-OCCSQVGLSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (2R)-1-({4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl}oxy)propan-2-yl (2S)-2-aminopropanoate
• IUPAC Traditional name: (2R)-1-({4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl}oxy)propan-2-yl (2S)-2-aminopropanoate
• Synonyms: BMS-582664; Brivanib alaninate(BMS-582664)

Database IDs

• CAS Number: 649735-63-7
• PubChem SID: 162037460
• PubChem CID: 11154925

CALCULATED PROPERTIES

• Acid pKa: 16.587137
• H Acceptors: 5
• H Donor: 2
• LogD (pH = 5.5): 1.6825836
• LogD (pH = 7.4): 3.2298245
• Log P: 3.501098
• Molar Refractivity: 127.0266 cm^3
• Polarizability: 45.822025 Å^3
• Polar Surface Area: 116.76 Å^2
• Rotatable Bonds: 8
• Lipinski's Rule of Five: true

PROPERTIES

Safety Information

• Storage Condition: -20°C

Pharmacology Properties

• Target: FGFR; VEGFR

Product Information

• Salt Data: Disodium

DETAILS

Selleck Chemicals - S1138

Research Area: Solid tumours,Liver cancer,Gastrointestinal cancer
Biological Activity:
BMS-582664, also named “brivanib alaninate”, is the alaninate salt of a VEGFR2 inhibitor BMS-540215. Brivanib is hydrolyzed to the active moiety BMS-540215 in vivo. BMS-540215 shows potent and selective inhibition of VEGFR and FGFR tyrosine kinases [1,2] . BMS-540215 is an ATP-competitive inhibitor of human VEGFR-2, with an IC50 of 25 nM and Ki of 26 nmol/L. In addition, it inhibits VEGFR-1 (IC50 =380nM) and VEGFR-3 (IC50 = 10 nM). BMS-540215 also showed good selectivity for FGFR-1 (IC50=148 nM), FGFR-2 (IC50 =125 nM), and FGFR-3 (IC50 = 68 nM). Furthermore,BMS-540215 has been shown to selectively inhibit the proliferation of endothelial cells stimulated by VEGF and FGF in vitro with IC50 values of 40 and 276 nM, respectively[3,4] .BMS-582664 was prepared in an effort to improve the aqueous solubility and oral bioavailability of the parent compound BMS-540215.References on Brivanib alaninate (BMS-582664)[1] Clin Cancer Res, 2008, 14:6146-6153[2] J. Med. Chem, 2008, 51:1976–1980[3] Cancer Res, 2007, 67:6899-6906[4] Journal of Medicinal Chemistry, April 6, 2006, 49:2143-2146

REFERENCES

• PG Smith et al. British Journal of Cancer. 2000