N-[2-(diethylamino)ethyl]-5-{[(3Z)-5-fluoro-2-oxo-2,3-dihydro-1H-indol-3-ylidene]methyl}-2,4-dimethyl-1H-pyrrole-3-carboxamide

• ChemBase ID: 1135
• Molecular Formular: C22H27FN4O2
• Molecular Mass: 398.4737832
• Monoisotopic Mass: 398.21180434
• SMILES: Fc1cc2/C(=C/c3[nH]c(c(c3C)C(=O)NCCN(CC)CC)C)/C(=O)Nc2cc1
• Canonical SMILES: CCN(CCNC(=O)c1c(C)[nH]c(c1C)/C=C/1\C(=O)Nc2c1cc(F)cc2)CC
• InChI: InChI=1S/C22H27FN4O2/c1-5-27(6-2)10-9-24-22(29)20-13(3)19(25-14(20)4)12-17-16-11-15(23)7-8-18(16)26-21(17)28/h7-8,11-12,25H,5-6,9-10H2,1-4H3,(H,24,29)(H,26,28)/b17-12-
• InChIKey: WINHZLLDWRZWRT-ATVHPVEESA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: N-[2-(diethylamino)ethyl]-5-{[(3Z)-5-fluoro-2-oxo-2,3-dihydro-1H-indol-3-ylidene]methyl}-2,4-dimethyl-1H-pyrrole-3-carboxamide
• IUPAC Traditional name: sunitinib
• Brand Name: Sutent; sunitinib; SU-11248
• Synonyms: SU11248; Sunitinib malate; Sutent; Sunitinib; N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide

Database IDs

• CAS Number: 557795-19-4
• MDL Number: MFCD09260778
• PubChem SID: 160964598; 46507140
• PubChem CID: 5329102

CALCULATED PROPERTIES

JChem

• Acid pKa: 11.462899
• H Acceptors: 3
• H Donor: 3
• LogD (pH = 5.5): -0.2940415
• LogD (pH = 7.4): 1.2792807
• Log P: 2.9273767
• Molar Refractivity: 116.2663 cm^3
• Polarizability: 42.123272 Å^3
• Polar Surface Area: 77.23 Å^2
• Rotatable Bonds: 7
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 3.24
• LOG S: -4.11
• Solubility (Water): 3.08e-02 g/l

PROPERTIES

Physical Property

• Hydrophobicity(logP): 2.5

Product Information

• Purity: 95+%; 98%

DETAILS

DrugBank - DB01268

• Drug Groups: approved; investigational
• Description: Sunitinib is an oral, small-molecule, multi-targeted receptor tyrosine kinase (RTK) inhibitor that was approved by the FDA for the treatment of renal cell carcinoma (RCC) and imatinib-resistant gastrointestinal stromal tumor (GIST) on January 26, 2006. Sunitinib inhibits cellular signaling by targeting multiple RTKs. These include all platelet-derived growth factor receptors (PDGF-R) and vascular endothelial growth factor receptors (VEGF-R). Sunitinib also inhibits KIT (CD117), the RTK that drives the majority of GISTs. In addition, sunitinib inhibits other RTKs including RET, CSF-1R, and flt3.
• Indication: For the treatment of advanced renal cell carcinoma as well as the treatment of gastrointestinal stromal tumor after disease progression on or intolerance to imatinib mesylate.
• Pharmacology: Sunitinib is an oral, small-molecule, multi-targeted receptor tyrosine kinase (RTK) inhibitor that was approved by the FDA on January 26, 2006.
• Affected Organisms: Humans and other mammals
• Biotransformation: Sunitinib is metabolized primarily by the cytochrome P450 enzyme, CYP3A4, to produce its primary active metabolite, which is further metabolized by CYP3A4.
• Absorption: Maximum plasma concentrations (Cmax) of sunitinib are generally observed between 6 and 12 hours (Tmax) following oral administration. Food has no effect on the bioavailability of sunitinib. Sunitinib may be taken with or without food.
• Half Life: Following administration of a single oral dose in healthy volunteers, the terminal half-lives of sunitinib and its primary active metabolite are approximately 40 to 60 hours and 80 to 110 hours, respectively.
• Protein Binding: Binding of sunitinib and its primary metabolite to human plasma protein in vitro was 95% and 90%, respectively.
• Elimination: Sunitinib is metabolized primarily by the cytochrome P450 enzyme, CYP3A4, to produce its primary active metabolite, which is further metabolized by CYP3A4. Elimination is primarily via feces. In a human mass balance study of [14C]sunitinib, 61% of the dose was eliminated in feces, with renal elimination accounting for 16% of the administered dose.
• Distribution: * 2230 L
• Clearance: * Oral cl=34 - 62 L/h
• References: Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, Oudard S, Negrier S, Szczylik C, Kim ST, Chen I, Bycott PW, Baum CM, Figlin RA: Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 2007 Jan 11;356(2):115-24. [Pubmed] ; Demetri GD, van Oosterom AT, Garrett CR, Blackstein ME, Shah MH, Verweij J, McArthur G, Judson IR, Heinrich MC, Morgan JA, Desai J, Fletcher CD, George S, Bello CL, Huang X, Baum CM, Casali PG: Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet. 2006 Oct 14;368(9544):1329-38. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

DrugBank - DB07417

Drug information: experimental

REFERENCES

• Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, Oudard S, Negrier S, Szczylik C, Kim ST, Chen I, Bycott PW, Baum CM, Figlin RA: Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 2007 Jan 11;356(2):115-24. Pubmed
• Demetri GD, van Oosterom AT, Garrett CR, Blackstein ME, Shah MH, Verweij J, McArthur G, Judson IR, Heinrich MC, Morgan JA, Desai J, Fletcher CD, George S, Bello CL, Huang X, Baum CM, Casali PG: Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet. 2006 Oct 14;368(9544):1329-38. Pubmed