Sorafenib

Base Information

• Chemical Name: Sorafenib
• CAS No.: 284461-73-0
• Molecular Formula: C21H16ClF3N4O3
• Molecular Weight: 464.831
• Hs Code.: 29350090
• European Community (EC) Number: 608-209-4
• NSC Number: 747971
• UNII: 9ZOQ3TZI87
• DSSTox Substance ID: DTXSID7041128
• Nikkaji Number: J1.961.269D
• Wikipedia: Sorafenib
• Wikidata: Q421136
• NCI Thesaurus Code: C61948
• RXCUI: 495881
• Pharos Ligand ID: 4DAR47Y95JGR
• Metabolomics Workbench ID: 42760
• ChEMBL ID: CHEMBL1336
• Mol file: 284461-73-0.mol

Synonyms:4-(4-(3-(4-Chloro-3-trifluoromethylphenyl)ureido)phenoxy)pyridine-2-carboxylic acid methyamide-4-methylbenzenesulfonate;BAY 43 9006;BAY 43-9006;BAY 439006;BAY 545 9085;BAY 545-9085;BAY 5459085;BAY 673472;BAY-545-9085;BAY-673472;BAY5459085;Nexavar;sorafenib;Sorafenib N Oxide;sorafenib N-oxide;sorafenib tosylate

Chemical Property of Sorafenib

Chemical Property:

• Appearance/Colour: light yellow solid
• Vapor Pressure: 4.76E-11mmHg at 25°C
• Melting Point: 202-204 °C
• Boiling Point: 523.3 °C at 760 mmHg
• PKA: 12.89±0.70(Predicted)
• Flash Point: 270.3 °C
• PSA: 92.35000
• Density: 1.454 g/cm³
• LogP: 6.08660
• Storage Temp.: -20°C Freezer
• Solubility.: Chloroform (Slightly), DMSO (Slightly)
• Water Solubility.: 100μg/L at 20℃
• XLogP3: 4.1
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 5
• Exact Mass: 464.0863026
• Heavy Atom Count: 32
• Complexity: 646

Purity/Quality:

85.0-99.8% ^*data from raw suppliers

Sorafenib ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xi
• Hazard Codes: Xi
• Statements: 68/20/21/22-37/38
• Safety Statements: 36-37-39

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antineoplastic Agents
• Canonical SMILES: CNC(=O)C1=NC=CC(=C1)OC2=CC=C(C=C2)NC(=O)NC3=CC(=C(C=C3)Cl)C(F)(F)F
• Recent ClinicalTrials: Serial Measurements of Molecular and Architectural Responses to Therapy (SMMART) PRIME Trial
• Recent EU Clinical Trials: AN OPEN LABEL, RANDOMISED, PHASE 2 STUDY TO EVALUATE THE SAFETY AND EFFICACY OF MTL-CEBPA ADMINISTERED IN COMBINATION WITH SORAFENIB OR SORAFENIB ALONE, IN TKI NA?VE PARTICIPANTS WITH PREVIOUSLY TREATED ADVANCED HEPATOCELLULAR CARCINOMA (HCC) AND HEPATITIS B OR HEPATITIS C VIRUS (OUTREACH2)
• Recent NIPH Clinical Trials: Randomized phase III trial of Sorafenib versus Lenvatinib as a second-line treatment after immune check point inhibitor for advanced hepatocellular carcinoma
• Uses: Sorafenib, an orally active potent multi-kinases inhibitor,was approved in the U.S. for the treatment of advanced renalcell carcinoma. The drug targets both tumor cell proliferationand tumor angiogenesis kinases that include RAF,VEGFR-2, VEGFR-3, PDGFR-??, KIT and FLT-3. Sorafenibis being jointly developed by Bayer and Onyx in phase IIItrials as a single agent for the treatment of advanced hepato-cellular carcinoma and in combination with carboplatin andpaclitaxel in patients with advanced metastatic melanoma.Phase II trials in combination with doxorubicin for thetreatment of advanced hepatocellular carcinoma are alsounder investigation. Additional phase II trials are ongoingfor non-small cell lung cancer (NSCLC) and in postmenopausalwomen with estrogen receptor and/or progesteronereceptor-positive metastatic breast cancer. In addition, theNational Cancer Institute (NCI) is evaluating the compoundboth as a single therapy agent and in combination with otheroncology agents in phase II trials for several cancer indications. A potent RAF kinase inhibitor. Antineoplastic Multiple kinase inhibitor targeting both RAF kinase and receptor tyrosine kinases that promote angiogensis. Antineoplastic. Sorafenib Tosylate (Bay 43-9006, Nexavar) is a small molecular inhibitor of VEGFR, PDGFR, c-Raf and B-Raf with IC50s of 18 nM, 10 nM, 3 nM and 15 nM, respectively. Sorafenib Tosylate (Bay 43-9006) is a multikinase inhibitor of Raf-1, B-Raf and VEGFR-2 with IC50 of 6 nM, 22 nM and 90 nM, respectively - See more at: http://www.selleckchem.com/products/Sorafenib-Tosylate.html#sthash.BjHEmCf3.dpuf
• Indications: It is indicated for the treatment of hepatocellular carcinoma and the treatment of advanced renal cell carcinoma (primary kidney cancer). Sorafenib (Nexavar(R), Bayer) was the first approved inhibitor targeting the vascular endothelial growth factor (VEGF) family kinases, which include VEGFR1, VEGR2, and VEGFR3. Sorafenib was originally approved for the treatment of renal cell carcinoma (RCC) in 2005, hepatocellular carcinoma in 2007, and locally recurrent or metastatic thyroid carcinoma refractory to radioactive iodine treatment in 2013. Six other approved inhibitors with VEGFRs as the main targets are sunitinib (Sutent(R), Pfizer) for RCC, soft tissue sarcoma, thyroid cancer,metastatic pancreatic tumors, gastrointestinal stromal tumor, and several other types of carcinomas; pazopanib (Votrient(R), GlaxoSmithKline) for RCC, soft tissue sarcoma, and thyroid cancer; axitinib (Inlyta(R), Pfizer) for RCC,thyroid cancer, and aplastic anemia, as well as T315I-mutant Bcr–Abl1-driven leukemia; regorafenib (Stivarga(R), Bayer) for gastrointestinal stromal tumors and colorectal cancer; nintedanib (Ofev(R), Boehringer Ingelheim) for the non-oncological indication of idiopathic pulmonary fibrosis; and lenvatinib (Lenvima(R), Eisai Inc.) for RCC and different types of thyroid cancers. Sunitinib, pazopanib, and lenvatinib bind to the “DFG-in”conformation of VEGFRs, while axitinib, regorafenib, and nintedanib bind to inactive VEGFRs adopting the “DFG-out”conformation.
• Description: Sorafenib is a small molecular inhibitor of several kinases involved in tumor angiogenesis and proliferation, including, but not limited to, Raf (IC50=12nM for Raf-1), VEGFR (IC50=90nM for VEGFR-2 and IC50=12nM for VEGFR-3), and platelet derived growth factor receptor (IC50=57nM for PDGFR-b). Specifically, sorafenib blocks tumor progression by inhibiting cellular proliferation that is dependent on activation of the MAPK pathway (Raf) and/or inhibiting tumor angiogenesis through VEGFR and/or PDGFR. While it may be effective in the treatment of a variety of tumors, the first approvable indication is for renal cell carcinoma. Overall, the drug appears to be well tolerated by the majority of patients at the 400 mg b.i.d. continuous dosing. As an inhibitor of multiple kinases vital for tumor progression, sorafenib may possess wide-spectrum antitumor properties and may emerge as an effective weapon against a variety of solid tumors.
• Clinical Use: Protein kinase inhibitor: Treatment of advanced renal cell carcinoma Treatment of hepatocellular carcinoma Treatment of thyroid cancer
• Drug interactions: Potentially hazardous interactions with other drugs Anticoagulants: may enhance effect of coumarins. Antipsychotics: avoid with clozapine (increased risk of agranulocytosis). Antivirals: avoid with boceprevir.

Technology Process of Sorafenib

There total 64 articles about Sorafenib 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: 97.9%

4-chloro-3-trifluoromethylphenylurea (343247-69-8) + [4-(4-bromophenoxy)(2-pyridyl)]-N-methylcarboxamide (1154243-75-0) → sorafenib (284461-73-0)

Guidance literature:

[4-(4-bromophenoxy)(2-pyridyl)]-N-methylcarboxamide; With potassium phosphate; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; In 1,4-dioxane; at 20 ℃; for 0.5h;

4-chloro-3-trifluoromethylphenylurea; In 1,4-dioxane; at 80 - 100 ℃; for 1h; Solvent; Reagent/catalyst;

Reference yield: 97.6%

4-(4-aminophenoxy)-N-methylpyridine-2-carboxamide (284462-37-9) + (4-chloro-3-trifluoromethyl aniline)carboxylic acid allyl ester → sorafenib (284461-73-0)

Guidance literature:

With 1-Methylpyrrolidine; In dichloromethane; at 30 ℃; for 24h; Solvent; Temperature;

Reference yield: 96.7%

4-[ ({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)amino]phenol (1129683-83-5) + 4-bromo-pyridine-2-carboxylic acid methyl amide (1209459-88-0) → sorafenib (284461-73-0)

Guidance literature:

4-[ ({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)amino]phenol; With 2,2,6,6-tetramethylheptane-3,5-dione; caesium carbonate; copper(l) chloride; In 1-methyl-pyrrolidin-2-one; at 50 - 60 ℃; for 0.5h;

4-bromo-pyridine-2-carboxylic acid methyl amide; In 1-methyl-pyrrolidin-2-one; for 2h; Reagent/catalyst; Reflux;

upstream raw materials:

4-(4-aminophenoxy)-N-methylpyridine-2-carboxamide

4-chloro-3-(trifluoromethyl)phenyl isocyanate

sorafenib tosylate

4-[ ({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)amino]phenol

Downstream raw materials:

BAY 67-3472

sorafenib ethane sulphonate

4-(4-{3-[4-chloro-3-(trifluoromethyl)phenyl]ureido}phenoxy)-N-methylpyridine-2-carboxamide methanesulphonate

4-(4-{3-[4-chloro-3-(trifluoromethyl)phenyl]ureido}phenoxy)-N-methylpyridine-2-carboxamide sulphate

Refernces

• 1、 Tanzadehpanah, Hamid,Bahmani, Asrin,Hosseinpour Moghadam, Neda,Gholami, Hamid,Mahaki, Hanie,Farmany, Abbas,Saidijam, Massoud. "Synthesis, anticancer activity, and β-lactoglobulin binding interactions of multitargeted kinase inhibitor sorafenib tosylate (SORt) using spectroscopic and molecular modelling approaches". . p. 117 - 128. Retrieved 2020/08/19.
• 2、 -. "Sorafenib hemicamsylate and processes for preparation thereof". Paragraph 0082-0086. . Retrieved 2020/05/26.