Pazopanib

Base Information

• Chemical Name: Pazopanib
• CAS No.: 444731-52-6
• Deprecated CAS: 790713-33-6
• Molecular Formula: C₂₁H₂₃N₇O₂S
• Molecular Weight: 437.525
• Hs Code.: 29350090
• NSC Number: 752782
• UNII: 7RN5DR86CK
• DSSTox Substance ID: DTXSID8048733
• Nikkaji Number: J2.417.435B
• Wikipedia: Pazopanib
• Wikidata: Q7157043
• NCI Thesaurus Code: C74547
• RXCUI: 714438
• Pharos Ligand ID: VAD1FZTYS37A
• Metabolomics Workbench ID: 65526
• ChEMBL ID: CHEMBL477772
• Mol file: 444731-52-6.mol

Synonyms:GW 780604;GW 786034B;GW-780604;GW-786034B;GW780604;GW786034B;pazopanib;Votrient

Chemical Property of Pazopanib

Chemical Property:

• Appearance/Colour: White powder
• Vapor Pressure: 4.26E-21mmHg at 25°C
• Melting Point: 285-289°C (dec.)
• Boiling Point: 728.814 °C at 760 mmHg
• PKA: 10.19±0.60(Predicted)
• Flash Point: 394.572 °C
• PSA: 127.41000
• Density: 1.40 g/cm³
• LogP: 4.99310
• Storage Temp.: Refrigerator
• Solubility.: Aqueous Acid (Slightly), DMSO (Slightly, Heated), Methanol (Slightly, Heated)
• XLogP3: 3.1
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 8
• Rotatable Bond Count: 5
• Exact Mass: 437.16339418
• Heavy Atom Count: 31
• Complexity: 717

Purity/Quality:

99.5% ^*data from raw suppliers

Pazopanib ^*data from reagent suppliers

Safty Information:

• Statements: 43-62/63
• Safety Statements: 36/37/39-28B

MSDS Files:

Useful:

• Drug Classes: Antineoplastic Agents
• Canonical SMILES: CC1=C(C=C(C=C1)NC2=NC=CC(=N2)N(C)C3=CC4=NN(C(=C4C=C3)C)C)S(=O)(=O)N
• Recent ClinicalTrials: Sequential Two-agent Assessment in Renal Cell Carcinoma Therapy: The START Trial
• Recent EU Clinical Trials: RAR-Immune: A randomised, comparative, prospective, multicentre study of the efficacy of nivolumab + ipilimumab versus pazopanib alone in patients with metastatic or unresectable advanced sarcoma of rare subtype
• Recent NIPH Clinical Trials: JCOG1802: A randomized phase II trial of 2nd line treatment for advanced soft tissue sarcoma comparing trabectedin, eribulin and pazopanib
• Description: Pazopanib is a multi-kinase inhibitor that inhibits the VEGF receptors VEGFR1, VEGFR2, and VEGFR3 (IC50s = 10, 30, and 47 nM, respectively, in a cell-free enzyme assay). It also inhibits PDGFRα, PDGFRβ, and c-Kit (IC50s = 71, 84, and 74 nM, respectively, in a cell-free enzyme assay) as well as additional receptor tyrosine kinases. Pazopanib inhibits upregulation of the surface adhesion proteins ICAM-1 and VCAM-1 induced by VEGF in multiple myeloma cells cocultured with human umbilical vein endothelial cells (HUVECs) and decreases multiple myeloma cell adhesion to HUVECs. It also inhibits proliferation of multiple myeloma cells cocultured with HUVECs. Pazopanib (30 and 100 mg/kg) reduces tumor growth, induces apoptosis, decreases angiogenesis, and increases survival in a multiple myeloma mouse xenograft model. Formulations containing pazopanib have been used in the treatment of cancer.
• Uses: Pazopanib Hydrochloride (GW786034, Votrient, Armala) is a novel multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFR, FGFR, c-Kit and c-Fms with IC50 of 10 nM, 30 nM, 47 nM, 84 nM, 74 nM, 140 nM and 146 nM, respectively. Pazopanib is a potent and selective multi-targeted receptor tyrosine kinase inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFR-α/β, and c-Kit. Pazopanib is a novel multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFR, FGFR, c-Kit and c-Fms with IC50 of 10 nM, 30 nM, 47 nM, 84 nM, 74 nM, 140 nM and 146 nM, respectively. An oral angiogenesis inhibitor targeting VEGFR and PDGFR.
• Clinical Use: Tyrosine kinase inhibitor: Treatment of metastatic renal cell carcinoma and soft tissue sarcoma
• Drug interactions: Potentially hazardous interactions with other drugs Antibacterials: avoid with clarithromycin, rifampicin and telithromycin. Antifungals: avoid with itraconazole, ketoconazole and voriconazole. Antipsychotics: avoid with clozapine (increased risk of agranulocytosis). Antivirals: avoid with atazanavir, boceprevir, indinavir, ritonavir and saquinavir. Grapefruit juice: avoid concomitant administration. Avoid concomitant use with other inhibitors or inducers of CYP3A4. Dose alterations may be required.

Technology Process of Pazopanib

There total 15 articles about Pazopanib 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: 97.0%

pazopanib hydrochloride (635702-64-6) → pazopanib (444731-52-6,790713-33-6)

Guidance literature:

With sodium carbonate; In methanol; water; at 20 ℃; for 5h; Product distribution / selectivity;

Reference yield: 90.0%

N-(2-chloropyrimidin-4-yl)-N-methyl-2,3-dimethyl-2H-indazole-6-amine (444731-75-3) + 5-amino-2-methylbenzenesulfonamide (6973-09-7) → pazopanib (444731-52-6,790713-33-6)

Guidance literature:

With hydrogenchloride; In water; isopropyl alcohol; at 85 ℃;

DOI:10.1111/cbdd.12243

Reference yield: 83.0%

C21H24N8O2S → pazopanib (444731-52-6,790713-33-6)

Guidance literature:

C₂₁H₂₄N₈O₂S; With tert.-butylnitrite; toluene-4-sulfonic acid; In acetonitrile; at 0 ℃;

With dichloro(1,5-cyclooctadiene)ruthenium(II); Triethoxysilane; In N,N-dimethyl-formamide; at 20 ℃;

upstream raw materials:

5-[[4-[(2,3-dimethyl-2H-indazol-6-yl)-N-methylamino]-2-pyrimidinyl]amino]-2-methylbenzenesulfonamide hydrochloride

N-(2-chloropyrimidin-4-yl)-N-methyl-2,3-dimethyl-2H-indazole-6-amine

5-amino-2-methylbenzenesulfonamide

pazopanib hydrochloride

Refernces

• 1、 -. "Preparation method and intermediate of Pazopanib". . . Retrieved 2018/04/03.
• 2、 Jia, Yuping,Zhang, Jian,Feng, Jinhong,Xu, Fuming,Pan, Huili,Xu, Wenfang. "Design, synthesis and biological evaluation of pazopanib derivatives as antitumor agents". . p. 306 - 316. Retrieved 2014/03/21.