Lenvatinib

Base Information

• Chemical Name: Lenvatinib
• CAS No.: 417716-92-8
• Deprecated CAS: 942407-57-0
• Molecular Formula: C21H19ClN4O4
• Molecular Weight: 426.859
• UNII: EE083865G2
• DSSTox Substance ID: DTXSID50194605
• Nikkaji Number: J2.624.265G
• Wikipedia: Lenvatinib
• Wikidata: Q6523413
• NCI Thesaurus Code: C95124
• RXCUI: 1603296
• Pharos Ligand ID: U3UTLYD2YFNQ
• Metabolomics Workbench ID: 152132
• ChEMBL ID: CHEMBL1289601
• Mol file: 417716-92-8.mol

Synonyms:4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-hydroxy-6-quinolinecarboxamide;4-(3-chloro-4-((cyclopropylaminocarbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide;4-(3-chloro-4-(N'-cyclopropylureido)phenoxy)-7-methoxyquinoline-6-carboxamide;E 7080;E-7080;E-7080 mesylate;E7080;E7080 mesylate;ER-203492-00;lenvatinib;lenvatinib mesilate;lenvatinib mesylate;lenvatinib metabolite M2;lenvatinib methanesulfonate;Lenvima;N-(4-((6-carbamoyl-7-methoxyquinolin-4-yl)oxy)-2-chlorophenyl)-N'-cyclopropylurea monomethanesulfonate

Chemical Property of Lenvatinib

Chemical Property:

• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.697
• Boiling Point: 627.242 °C at 760 mmHg
• PKA: 13.09±0.70(Predicted)
• Flash Point: 333.144 °C
• PSA: 115.57000
• Density: 1.469 g/cm³
• LogP: 5.23610
• Storage Temp.: -20°C
• Solubility.: Soluble in DMSO (up to 20 mg/ml)
• XLogP3: 2.8
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 6
• Exact Mass: 426.1094828
• Heavy Atom Count: 30
• Complexity: 634

Purity/Quality:

>95% ^*data from raw suppliers

Lenvatinib ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antineoplastic Agents
• Canonical SMILES: COC1=CC2=NC=CC(=C2C=C1C(=O)N)OC3=CC(=C(C=C3)NC(=O)NC4CC4)Cl
• Recent ClinicalTrials: A Study of Belzutifan (MK-6482) in Combination With Lenvatinib Versus Cabozantinib for Treatment of Renal Cell Carcinoma (MK-6482-011)
• Recent EU Clinical Trials: A Phase 1/2 Open-Label, Umbrella Platform Design Study of Investigational Agents With Pembrolizumab (MK-3475) in Participants With Advanced Esophageal Cancer Previously Exposed to PD-1/PD-L1 Treatment (KEYMARKER-U06): Substudy 06B.
• Recent NIPH Clinical Trials: An Open-label, Randomized Phase 3 Study of Immune and Targeted Combination Therapies, as First-line Treatment in Participants with Advanced ccRCC
• Description: Lenvatinib is an inhibitor of the receptor tyrosine kinases VEGF receptor 2 (VEGFR2) and VEGFR3 (IC50s = 4 and 5.2 nM, respectively). It also inhibits the related kinases VEGFR1, FGFR1, PDGFRα, PDGFRβ and Kit (IC50s = 22, 46, 51, 39, and 100 nM, respectively). Lenvatinib (30 mg/kg, twice per day) reduces tumor growth in an H146 small cell lung cancer mouse xenograft model and induces tumor regression when administered at a dose of 100 mg/kg twice per day. Formulations containing lenvatinib have been used in the treatment of differentiated thyroid cancer, renal cell carcinoma, and hepatocellular carcinoma.
• Uses: E7080 (Lenvatinib) is a multi-target inhibitor of VEGFR2 and VEGFR3 with IC50 of 4 nM and 5.2 nM, respectively. Lenvatinib is an orally active inhibitor of multiple receptor tyrosine kinases including VEGF, FGF and SCF receptors.

Technology Process of Lenvatinib

There total 43 articles about Lenvatinib 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: 98.0%

{4-[(6-carbamoyl-7-methoxy-4-quinolyl)oxy]-2-chlorophenyl}amino-carboxylic acid phenyl ester (417722-95-3) + Cyclopropylamine (765-30-0) → lenvatinib (417716-92-8)

Guidance literature:

at 20 ℃; for 4h;

Reference yield: 98.0%

C22H17ClN4O7 + Cyclopropylamine (765-30-0) → lenvatinib (417716-92-8)

Guidance literature:

at 20 ℃; for 4h; Temperature;

Reference yield: 96.3%

4‐chloro‐7‐methoxyquinoline‐6‐carboxamide (417721-36-9) + 1-(2-chloro-4-hydroxyphenyl)-3-cyclopropyl urea (796848-79-8) → lenvatinib (417716-92-8)

Guidance literature:

With potassium tert-butylate; In dimethyl sulfoxide; at 20 - 65 ℃; for 22h; Product distribution / selectivity;

upstream raw materials:

4‐chloro‐7‐methoxyquinoline‐6‐carboxamide

1-(2-chloro-4-hydroxyphenyl)-3-cyclopropyl urea

{4-[(6-carbamoyl-7-methoxy-4-quinolyl)oxy]-2-chlorophenyl}amino-carboxylic acid phenyl ester

Cyclopropylamine

Downstream raw materials:

4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide p-toluenesulfonate

4-[3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy]-7-methoxy-6-quinoline-carboxamide methanesulfonate

4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide ethanesulfonate

4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide hydrochloride

Refernces

• 1、 Sadineni, Ravi Kumar,Rapolu, Rajesh Kumar,Raju, V. V. N. K. V. Prasada,Srinivasu,Malladi, Sireesha,Mulakayala, Naveen. "Novel method for the synthesis of lenvatinib using 4-nitrophenyl cyclopropylcarbamate and their pharmaceutical salts". . p. 1475 - 1483. Retrieved 2020/11/05.
• 2、 -. "Synthetic method of anti-cancer drug lenvatinib". Paragraph 0010. . Retrieved 2021/01/25.