Crizotinib

Base Information

• Chemical Name: Crizotinib
• CAS No.: 877399-52-5
• Deprecated CAS: 912279-98-2
• Molecular Formula: C₂₁H₂₂Cl₂FN₅O
• Molecular Weight: 450.343
• Hs Code.: 29333990
• European Community (EC) Number: 638-814-9
• UNII: 53AH36668S
• ChEMBL ID: CHEMBL601719
• DSSTox Substance ID: DTXSID701009329
• Metabolomics Workbench ID: 63318
• NCI Thesaurus Code: C74061
• Nikkaji Number: J2.735.431I
• NSC Number: 749005
• Pharos Ligand ID: C52GL3ADX4W8
• RXCUI: 1148495
• Wikidata: Q5186964
• Wikipedia: Crizotinib
• Mol file: 877399-52-5.mol

Synonyms:crizotinib;PF 02341066;PF 2341066;PF-02341066;PF-2341066;PF02341066;PF2341066;xalkori

Chemical Property of Crizotinib

Chemical Property:

• Vapor Pressure: 0mmHg at 25°C
• Melting Point: 192 °C
• Refractive Index: 1.673
• Boiling Point: 599.177 °C at 760 mmHg
• PKA: 9.81±0.10(Predicted)
• Flash Point: 316.171 °C
• PSA: 77.99000
• Density: 1.475 g/cm³
• LogP: 5.94770
• Storage Temp.: room temp
• Solubility.: Soluble in DMSO (up to 25 mg/ml with warming) or in Ethanol (up to 25 mg/ml with warming)
• XLogP3: 3.7
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 5
• Exact Mass: 449.1185439
• Heavy Atom Count: 30
• Complexity: 558

Purity/Quality:

99% ^*data from raw suppliers

Crizotinib ≥99%(HPLC) ^*data from reagent suppliers

Safty Information:

• Safety Statements: 24/25

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antineoplastic Agents
• Canonical SMILES: CC(C1=C(C=CC(=C1Cl)F)Cl)OC2=C(N=CC(=C2)C3=CN(N=C3)C4CCNCC4)N
• Isomeric SMILES: C[C@H](C1=C(C=CC(=C1Cl)F)Cl)OC2=C(N=CC(=C2)C3=CN(N=C3)C4CCNCC4)N
• Recent ClinicalTrials: Crizotinib (Xalkori) Expanded Access Protocol For The Treatment Of Adult Or Pediatric Patients
• Recent EU Clinical Trials: CRIZOTINIB MASTER PROTOCOL: AN OPEN-LABEL CONTINUATION STUDY FOR PARTICIPANTS CONTINUING FROM PFIZER-SPONSORED CRIZOTINIB CLINICAL STUDIES
• Recent NIPH Clinical Trials: Crizotinib Continuation Clinical Study
• General Description: Crizotinib is an ALK inhibitor used in the treatment of ALK-positive non-small cell lung cancer (NSCLC), but resistance mutations such as G1202R can limit its efficacy. Research has focused on developing next-generation inhibitors, such as modified ceritinib derivatives, to overcome this resistance by targeting crizotinib-resistant mutants with improved potency and pharmacokinetic properties.

Technology Process of Crizotinib

There total 64 articles about Crizotinib 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: 99.6%

C31H38Cl2FN5O5 (1569895-72-2) → crizotinib (877399-52-5)

Guidance literature:

With hydrogenchloride; In ethanol; dichloromethane; water; at 0 - 20 ℃; for 12h;

Reference yield: 98.0%

C36H46Cl2FN5O7 → crizotinib (877399-52-5)

Guidance literature:

With hydrogenchloride; In 1,4-dioxane; dichloromethane; at 20 ℃; for 12h; Solvent;

Reference yield: 97.8%

tert-butyl 4-(4-(6-((tert-butoxycarbonyl)amino)-5-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate → (+/-)-PF023401066 (877400-66-3,877399-52-5)

Guidance literature:

With hydrogenchloride; In ethanol; dichloromethane; water; at 20 ℃; for 12h; Reagent/catalyst; Solvent;

upstream raw materials:

4-(4-{6-amino-5-[(R)-1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester

(S)‐1‐(2,6-dichloro-3-fluorophenyl)ethanol

5-bromo-3-[1 (R)-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-2-ylamine

tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate

Refernces

Replacing the terminal piperidine in ceritinib with aliphatic amines confers activities against crizotinib-resistant mutants including G1202R

10.1016/j.ejmech.2016.11.046

The research explores the development of new ALK inhibitors to address resistance issues in non-small cell lung cancer (NSCLC) patients. The study focuses on modifying ceritinib by replacing its piperidine fragment with diverse aliphatic amines to improve its efficacy against crizotinib-resistant mutants, particularly the highly resistant G1202R mutant. The researchers synthesized and evaluated a series of compounds, with compound 10 (KRCA-764) showing promising activities against both wild-type ALK and crizotinib-resistant mutants, including G1202R, with an IC50 of 1.8 nM. This compound also exhibited better pharmacokinetic profiles than ceritinib. Key chemicals involved in the synthesis included 4-methyl-2-nitroanisole, phenylthioacetonitrile, sodium hydroxide, Pd/C, and various amines. The study utilized enzymatic and cell-based assays to evaluate the inhibitory activities of the synthesized compounds, and molecular docking studies were performed to understand the binding modes. In vivo xenograft studies in mice demonstrated that compound 10 had similar potency to ceritinib, suggesting further optimization could lead to clinical candidates capable of overcoming ALK mutant resistance.