9000. Sunitinib

Nomenclature

CAS number: 557795-19-4
N-[2-(Diethylamino)ethyl]-5-[(Z)-(5-fluoro-1,2-dihydro-2-oxo-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide; 5-[5-fluoro-2-oxo-1,2-dihydroindol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide.
C22H27FN4O2; mol wt 398.47.
C 66.31%, H 6.83%, F 4.77%, N 14.06%, O 8.03%.

Description and references

Tyrosine kinase inhibitor targeting VEGF-R1, VEGF-R2, VEGF-R3, PDGF-Rα, PDGF-Rβ, KIT, FLT3, CSF-1R, and RET. Prepn: P. C. Tang et al., WO 0160814 (2001 to Sugen); eidem, US 6573293 (2003 to Sugen; Pharmacia & Upjohn); and kinase inhibition activity: L. Sun et al., J. Med. Chem. 46, 1116 (2003). Pharmacology: D. B. Mendel et al., Clin. Cancer Res. 9, 327 (2003). Clinical pharmacokinetics and evaluation in acute myeloid leukemia: A.-M. O'Farrell et al., ibid. 5465. LC-MS-MS determn in biological samples: S. Barattè et al., J. Chromatogr. A 1024, 87 (2004). Formulation development: A. Sistla et al., Drug Dev. Ind. Pharm. 30 19 (2004). Review of development and therapeutic potential: K. M. Sakamoto, Curr. Opin. Investig. Drugs 5, 1329-1339 (2004); of clinical evaluation in solid tumors: R. J. Motzer et al., Expert Opin. Invest. Drugs 15, 553-561 (2006).

Chemical structure

Properties

Orange solid. pKa 8.5. Log P (octanol/water): 3.1. Soly at 22° (μg/ml): 2582 in 20mM KCl/HCl buffer (pH 2); 364 in 20 mM phosphate buffer (pH 6).

Derivative

Maleate.

Nomenclature

CAS number: 341031-54-7
SU-11248; Sutent (Pfizer).
C22H27FN4O2.C4H6O5; mol wt 532.56.
C 58.64%, H 6.25%, F 3.57%, N 10.52%, O 21.03%.

Properties

Yellow to orange powder. pKa 8.95. Soly in aq. media (pH 1.2-6.8): >25 mg/ml. Log P (octanol/water): 5.2 (pH 7).

Therapeutic Category

Antineoplastic.

Keywords

Antineoplastic; Tyrosine Kinase Inhibitors