Pazopanib Hydrochloride

Base Information

• Chemical Name: Pazopanib Hydrochloride
• CAS No.: 635702-64-6
• Molecular Formula: C21H23N7O2S.ClH
• Molecular Weight: 473.98
• European Community (EC) Number: 619-728-0
• UNII: 33Y9ANM545
• ChEMBL ID: CHEMBL1201733
• DSSTox Substance ID: DTXSID70212956
• NCI Thesaurus Code: C60779
• NSC Number: 737754
• RXCUI: 732187
• Wikidata: Q27888072
• Mol file: 635702-64-6.mol

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

Chemical Property of Pazopanib Hydrochloride

Chemical Property:

• Boiling Point: 728.8 °C at 760 mmHg
• Flash Point: 394.6 °C
• PSA: 127.41000
• LogP: 5.79510
• Storage Temp.: Hygroscopic, Refrigerator, under inert atmosphere
• Solubility.: Acetonitrile (Slightly), DMSO (Slightly)
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 8
• Rotatable Bond Count: 5
• Exact Mass: 473.1400719
• Heavy Atom Count: 32
• Complexity: 717

Purity/Quality:

99% ^*data from raw suppliers

5-{4-[(2,3-Dimethyl-2H-indazol-6-yl)-methyl-amino]-pyrimidin-2-ylamino}-2-methyl-benzenesulfonamide hydrochloride ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• 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.Cl
• Recent ClinicalTrials: Pazopanib Hydrochloride in Treating Patients With Progressive Carcinoid Tumors
• 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
• Description: The growth of solid tumors is dependent on angiogenesis, the process wherein new capillaries are formed from existing blood vessels. VEGF is one of the most important inducers of angiogenesis and expressed at high levels by most tumors. Hence, the inhibition of VEGF or its receptor signaling system is an attractive target for cancer therapeutics. The most studied and developed inhibitors are monoclonal antibodies that neutralize VEGF (e.g., bevacizumab), anti-VEGF ribozymes (e.g., angiozyme), and small-molecule VEGFR kinase inhibitors (e.g., sunitinib, sorafenib). Pazopanib is the latest VEGFR kinase inhibitor to reach the market. It is indicated for the oral treatment of advanced RCC. The biological functions of the VEGF family are mediated by activation of three structurally homologous tyrosine kinase receptors, VEGFR-1, VEGFR-2, and VEGFR3. In vitro, pazopanib inhibits VEGFR-1, VEGFR-2, and VEGFR-3 with IC50 values of 10, 30, and 47 nM, respectively. In addition, it inhibits several of the closely related tyrosine receptor kinases, including platelet-derived growth-factor receptor β(PDGFR-β), c-kit, and fibroblast growth factor receptor-1 (FGFR1) with IC50 values of 84, 74, and 140 nM, respectively. In human umbilical vein endothelial cells (HUVEC), pazopanib inhibits VEGF-induced proliferation more potently than basic fibroblast growth factor (bFGF)-stimulated proliferation (IC50 = 21 nM vs. 721 nM) and concentration-dependently inhibits VEGF-induced VEGFR-2 phosphorylation (IC50 = 7 nM). It also potently inhibits angiogenesis in Matrigel plug and corneal micropocket assays. The most common adverse events associated with pazopanib were diarrhea, hypertension, hair depigmentation, nausea, anorexia, and vomiting.
• Uses: Pazopanib (GW786034) 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 - See more at: http://www.selleckchem.com/products/Pazopanib-Hyd The Hydrochloride salt of Pazopanib (P210925) a oral angiogenesis inhibitor targeting VEGFR and PDGFR.
• Clinical Use: Pazopanib is a potent and selective multi-targeted receptor tyrosine kinase inhibitor of VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-a/b, and c-kit that blocks tumor growth and inhibits angiogenesis. It was approved for renal cell carcinoma by the U.S. Food and Drug Administration in 2009 and is marketed under the trade name Votrient by the drug’s manufacturer, GlaxoSmithKline.

Technology Process of Pazopanib Hydrochloride

There total 12 articles about Pazopanib Hydrochloride 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: 77.0%

N-(2-chloropyrimidin-4-yl)-N-methyl-2,3-dimethyl-2H-indazole-6-amine (444731-75-3) + 2-amino-5-methyl-benzenesulfonamide (609-55-2) → pazopanib hydrochloride (635702-64-6)

Guidance literature:

With hydrogenchloride; In water; isopropyl alcohol; Heating / reflux;

Reference yield:

N,2,3-trimethyl-2H-indazole-6-amine (1376676-65-1) + 5-(4-chloropyrimidin-2ylamino)-2-methylbenzenesulfonamide (1379982-43-0) → pazopanib hydrochloride (635702-64-6)

Guidance literature:

N,2,3-trimethyl-2H-indazole-6-amine; 5-(4-chloropyrimidin-2ylamino)-2-methylbenzenesulfonamide; In ethanol; for 3h; Reflux;

With hydrogenchloride; In ethanol; water; for 10h; Reflux;

Reference yield:

5-amino-2-methylbenzenesulfonamide (6973-09-7) + N-(2-chloropyrimidin-1-yl)-N,2,3-trimethyl-2H-indazol-6-amine → 5-[[4-[(2,3-dimethyl-2H-indazol-6-yl)-N-methylamino]-2-pyrimidinyl]amino]-2-methylbenzenesulfonamide hydrochloride (635702-64-6)

Guidance literature:

With hydrogenchloride; In acetonitrile; at 25 - 30 ℃; Concentration; Temperature; Reflux;

upstream raw materials:

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

2-amino-5-methyl-benzenesulfonamide

N,2,3-trimethyl-2H-indazole-6-amine

5-(4-chloropyrimidin-2ylamino)-2-methylbenzenesulfonamide

Downstream raw materials:

pazopanib

Refernces

• 1、 -. "A NOVEL PROCESS FOR PREPARATION OF PAZOPANIB HYDROCHLORIDE". . . Retrieved 2021/08/20.
• 2、 -. "AN IMPROVED PROCESS FOR THE PREPARATION OF PAZOPANIB OR A PHARMACEUTICALLY ACCEPTABLE SALT THEREOF". . . Retrieved 2016/10/17.