Cabozantinib

Base Information

• Chemical Name: Cabozantinib
• CAS No.: 849217-68-1
• Molecular Formula: C28H24FN3O5
• Molecular Weight: 501.514
• Hs Code.: 2933499090
• Mol file: 849217-68-1.mol

Synonyms:N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide; 1-N-[4-(6,7-dimethoxyquinolin-4-yl)oxyphenyl]-1-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide; cyclopropane-1,1-dicarboxylic acid [4-(6,7-dimethoxy-quinoline-4-yloxy)-phenyl]-amide (4-fluoro-phenyl)-amide; [14C]-Cabozantinib; UNII-1C39JW444G; Cometriq; XL 184; Cabozantinib; 查看更多英文别名 收起

Chemical Property of Cabozantinib

Chemical Property:

• Boiling Point: 758.075 °C at 760 mmHg
• PKA: 13.86±0.70(Predicted)
• Flash Point: 412.269 °C
• PSA: 98.78000
• Density: 1.397 g/cm³
• LogP: 5.68680
• Storage Temp.: -20°C
• Solubility.: Soluble in DMSO

Purity/Quality:

99.5% + ^*data from raw suppliers

XL184 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Description: Cabozantinib was approved inNovember 2012 for the treatment of patients with progressive, unresectable, locally advanced, or metastatic medullary thyroid cancer (MTC). Cabozantinib was granted orphan drug status by the FDA to facilitate development of newtreatment options for patients with MTC. It is a member of a class of tyrosine kinase inhibitors (TKIs) with nanomolar pan-inhibitory activity against VEGFR2, MET, and RET among others. Inhibition of the VEGF pathway has been shown preclinically to initially slow tumor growth, but rapid revascularization is followed by aggressive tumor growth. The MET pathway has been implicated in the development of VEGF resistance, so dual VEGF/MET activity is viewed as desirable. In addition, mutations in RET play a particular role in MTC, with 25% of the tumors inheriting a germlinemutation in the proto-oncogene, so multiple tyrosine kinase inhibition may be viewed as particularly beneficial for the treatment of MTC.
• Uses: Cabozantinib (XL184, BMS-907351) is a potent VEGFR2 inhibitor with IC50 of 0.035 nM and also inhibits c-Met, Ret, Kit, Flt-1/3/4, Tie2, and AXL with IC50 of 1.3 nM, 4 nM, 4.6 nM, 12 nM/11.3 nM/6 nM, 14.3 nM and 7 nM, respectively XL184 can be used in biological study. Computational network biological approach based on pathway cross-talk inhibition identified new synergistic drug combinations using raloxifene and cabozantinib for treatment of human breast cancer in xenograft mouse model. Potent c-MET inhibitor.
• Clinical Use: Cabozantinib (PF-06463922; brand name Cabometyx; Exelixis, Alameda, CA) is an oral multikinase inhibitor with CNS penetration. It is FDA approved for use in medullary thyroid cancer and as a second-line agent in advanced renal cell carcinoma. In vitro studies found it to exhibit excellent activity against both the wild-type ROS1 fusion and the G2032R and G2026M mutations at concentrations less than 30?nmol/L—a dose much lower than what is clinically achievable [71, 91]. It has been found to inhibit CD74-ROS1-transformed Ba/F3 cells with more potency than entrectinib, brigatinib, lorlatinib [92], or foretinib [71].
• Drug interactions: Potentially hazardous interactions with other drugs Antibacterials: concentration possibly increased by clarithromycin and erythromycin; concentration reduced by rifampicin - avoid. Antiepileptics: concentration possibly reduced by carbamazepine, fosphenytoin, phenobarbital, phenytoin and primidone - avoid. Antipsychotics: avoid with clozapine - increased risk of agranulocytosis.

Technology Process of Cabozantinib

There total 49 articles about Cabozantinib 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: 100.0%

Cabozantinib malate salt (1140909-48-3) → cabozantinib (849217-68-1)

Guidance literature:

With sodium hydrogencarbonate; In water; ethyl acetate; at 45 ℃; for 2h;

Reference yield: 98.8%

1-(4-fluorophenylaminoformyl)cyclopropane carboxamide + 4-((6,7-dimethylquinolin-4-yl)oxy)phenylboronic acid → cabozantinib (849217-68-1)

Guidance literature:

With copper(II) acetate monohydrate; potassium carbonate; In methanol; for 10h; Reflux;

Reference yield: 98.6%

1-(4-fluorophenylaminoformyl)cyclopropane carboxamide + 6,7-Dimethoxy-4-(4-bromophenoxy)quinoline → cabozantinib (849217-68-1)

Guidance literature:

With Cu/SiO₂; In dimethyl sulfoxide; for 15h; Reflux;

upstream raw materials:

6,7-dimethoxyquinolin-4-yl trifluoromethanesulfonate

N-(4-fluorophenyl)-N'-(4-hydroxyphenyl)cyclopropane-1,1-dicarboxamide

4-((6,7-dimethoxyquinolin-4-yl)oxy)aniline

4-fluoroaniline

Downstream raw materials:

Cabozantinib malate salt

cabozantinib-N-oxide

Refernces

• 1、 -. "Synthesis method of cabozantinib and intermediate thereof". Paragraph 0124; 0131-0133. . Retrieved 2021/02/24.
• 2、 -. "Method of Treating Cancer". Paragraph 0110; 0121-0122; 0126; 0140-0145. . Retrieved 2020/11/30.