Sunitinib

Base Information

• Chemical Name: Sunitinib
• CAS No.: 557795-19-4
• Deprecated CAS: 326914-13-0
• Molecular Formula: C22H27FN4O2
• Molecular Weight: 398.48
• Hs Code.: 29337900
• NSC Number: 750690
• UNII: V99T50803M
• Nikkaji Number: J2.036.576E,J1.942.549E
• Wikipedia: Sunitinib
• Wikidata: Q417542,Q27163278
• NCI Thesaurus Code: C71622
• RXCUI: 357977
• Pharos Ligand ID: T16444CNC2AA
• Metabolomics Workbench ID: 43473
• ChEMBL ID: CHEMBL535
• Mol file: 557795-19-4.mol

Synonyms:5-(5-fluoro-2-oxo-1,2-dihydroindolylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide;SU 011248;SU 11248;SU-011248;SU-11248;SU011248;SU11248;sunitinib;sunitinib malate;Sutent

Chemical Property of Sunitinib

Chemical Property:

• Appearance/Colour: yellow solid
• Vapor Pressure: 3.13E-23mmHg at 25°C
• Melting Point: 189-191 °C
• Boiling Point: 572.136 °C at 760 mmHg
• PKA: 8.5(at 25℃)
• Flash Point: 299.818 °C
• PSA: 77.23000
• Density: 1.23 g/cm³
• LogP: 3.86380
• Storage Temp.: 2-8°C
• Solubility.: Chloroform (Slightly), Methanol (Slightly)
• XLogP3: 2.6
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 7
• Exact Mass: 398.21180428
• Heavy Atom Count: 29
• Complexity: 636

Purity/Quality:

99% ^*data from raw suppliers

Sunitinib Maleate ^*data from reagent suppliers

Safty Information:

• Safety Statements: 24/25

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antineoplastic Agents
• Canonical SMILES: CCN(CC)CCNC(=O)C1=C(NC(=C1C)C=C2C3=C(C=CC(=C3)F)NC2=O)C
• Isomeric SMILES: CCN(CC)CCNC(=O)C1=C(NC(=C1C)/C=C\2/C3=C(C=CC(=C3)F)NC2=O)C
• Recent ClinicalTrials: Serial Measurements of Molecular and Architectural Responses to Therapy (SMMART) PRIME Trial
• Recent EU Clinical Trials: Phase 1b/3 global, randomized, controlled, open-label trial comparing treatment with RYZ101 to standard of care (SoC) therapy in subjects with inoperable, advanced, somatostatin receptor expressing (SSTR+), well-differentiated gastro-enteropancreatic neuroendocrine tumors (GEP-NETs) that have progressed following prior treatment with 177Lu-labelled somatostatin analogue (177Lu-SSA) therapy (ACTION-1)
• Recent NIPH Clinical Trials: A phase 1 study of pimitespib and imatinib in patients with GIST
• Description: Sunitinib is an inhibitor of multiple receptor tyrosine kinases (RTKs) involved in tumor proliferation and angiogenesis, including platelet-derived growth factor receptors (PDGFR), vascular endothelial growth factor receptors (VEGFR), and stem cell factor receptor (KIT). It was launched as an oral treatment for gastrointestinal stromal tumors (GIST) and advanced renal-cell carcinoma (RCC). In vitro, sunitib inhibits VEGFR2, PDGFRα, PDGFRβ, KIT, and FLT3 receptors with IC50 values in the 4–14nM range, and the ligand-dependent autophosphorylation of VEGFR2 and PDGFRb with IC50s of approximately 10 nM. In addition, it inhibits the growth of tumor cells expressing dysregulated target RTKs in vitro and inhibits PDGFRb- and VEGFR2-dependent tumor angiogenesis in vivo. Sunitinib exhibits broad and potent antitumor activity, causing regression in murine models of human epidermal (A431), colon (Colo205 and HT-29), lung (NCI-H226 and H460), breast (MDA-MB-435), prostate (PC3-3M-luc), and renal (786-O) cancers, and suppressing or delaying the growth of many others, including the C6 rat and SF763 T human glioma xenografts and B16 melanoma lung cancer.
• Uses: A multi-kinase inhibitor targeting several receptor tyrosine kinases (RTK). Antineoplastic Sunitinib Malate is a multi-targeted RTK inhibitor targeting VEGFR2 (Flk-1) and PDGFRβ with IC50 of 80 nM and 2 nM, and also inhibits c-Kit.
• Clinical Use: Tyrosine kinase inhibitor: Treatment of metastatic renal cell carcinoma (MRCC), gastrointestinal stromal tumours (GIST) and pancreatic neuroendocrine tumours (pNET)
• Drug interactions: Potentially hazardous interactions with other drugs Antipsychotics: avoid with clozapine (increased risk of agranulocytosis). Antivirals: avoid concomitant use with boceprevir. Avoid concomitant use with other inhibitors or inducers of CYP3A4. Dose alterations may be required.

Technology Process of Sunitinib

There total 40 articles about Sunitinib which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 99.5%

sunitinib mesylate → sunitinib (557795-19-4,326914-13-0)

Guidance literature:

With sodium hydroxide; In water; at 80 ℃; pH=8 - 9;

Reference yield: 97.3%

5-fluoroindol-2(3H)-one (56341-41-4) + N-(2-(diethylamino)ethyl)-5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxamide (356068-86-5) → sunitinib (557795-19-4,326914-13-0)

Guidance literature:

With piperidine; In toluene; for 3h; Solvent; Reagent/catalyst; Reflux;

DOI:10.1007/s11164-015-1939-z

Reference yield: 88.0%

(Z)-3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl 5-((5-fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxylate (452105-55-4) + N,N-diethylethylenediamine (100-36-7) → sunitinib (557795-19-4,326914-13-0)

Guidance literature:

In N,N-dimethyl-formamide; acetonitrile; at 25 ℃; for 1h;

upstream raw materials:

N,N-diethylethylenediamine

5-((Z)-(5-fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid

5-fluoroindol-2(3H)-one

N-[2-(diethylamino)ethyl]-3-oxobutanamide

Downstream raw materials:

sunitinib malate

5-(5-Fluoro-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid(2-diethylamino-ethyl)-amide

Refernces

• 1、 Backos, Donald S.,Casalvieri, Kimberly A.,Jordan, Craig T.,Matheson, Christopher J.,Minhajuddin, Mohammed,Reigan, Philip. "Substituted oxindol-3-ylidenes as AMP-activated protein kinase (AMPK) inhibitors". . . Retrieved 2020/04/22.
• 2、 Paludetto, Marie-No?lle,Bijani, Christian,Puisset, Florent,Bernardes-Génisson, Vania,Arellano, Cécile,Robert, Anne. "Metalloporphyrin-Catalyzed Oxidation of Sunitinib and Pazopanib, Two Anticancer Tyrosine Kinase Inhibitors: Evidence for New Potentially Toxic Metabolites". . p. 7849 - 7860. Retrieved 2018/09/06.