Ponatinib

Base Information

• Chemical Name: Ponatinib
• CAS No.: 943319-70-8
• Molecular Formula: C₂₉H₂₇F₃N₆O
• Molecular Weight: 532.568
• Hs Code.: 29335990
• Mol file: 943319-70-8.mol

Synonyms:AP24534(Ponatinib);

Chemical Property of Ponatinib

Chemical Property:

• PKA: 12.99±0.70(Predicted)
• PSA: 65.77000
• Density: 1.292 g/cm³
• LogP: 4.40480
• Storage Temp.: -20°C
• Solubility.: Soluble in DMSO (up to 50 mg/ml) or in Ethanol (up to 25 mg/ml with warming).

Purity/Quality:

99%min ^*data from raw suppliers

AP 24534 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Drug Interactions: CYP3A4 enzyme can promote the metabolism of ponatinib. So during the treatment, we should avoid using potent CYP3A4 inhibitors. Information related to the pharmacological effects, side effects, drug contraindications, etc of ponatinib is edited by Shiyan from lookchem. (2015-10-23)
• Description: Ponatinib (943319-70-8) is a highly potent pan-Bcr-Abl and multikinase inhibitor, suppressing the activity of native Bcr-Abl (IC50=0.37 nM) as well as the mutants T315I (IC50=2 nM), Q252H (IC50=0.44 nM), Y253F (IC50=0.3 nM), M351T (IC50=0.3 nM) and H396P (IC50=0.34 nM).1??Also inhibits PDGFRα, c-Src and c-Kit (IC50=1.1, 5.4 and 12.5 nM respectively)2?as well as FGFR-mediated signaling (IC50<40 nM)3. Protects against influenza A virus-induced death by suppressing cytokine storm in mouse models..4
• Uses: AP24534 is a novel potent, orally available small molecule multitargeted kinase inhibitor with IC50 of 0.37, 2, 1.5, 2.2, 1.1, 1and 0.24 nM for native pan-BCR-ABL, mutated form, VEGFR2, FGFR1, PDGFRα, mutant FLT3 phosphorylation and LYN. Ponatinib (AP24534) is a novel potent, orally available small molecule multitargeted kinase inhibitor. Ponatinib inhibits both native and mutant BCR-ABL. Ponatinib is used in the treatment of chronic myeloid leukemia (CML) with BCR-ABL kinase inhibitors. Ponatinib (AP24534) is a novel, potent multi-target inhibitor of Abl, PDGFRα, VEGFR2, FGFR1 and Src with IC50 of 0.37 nM, 1.1 nM, 1.5 nM, 2.2 nM and 5.4 nM, respectively
• Clinical Use: Protein kinase inhibitor: Treatment of chronic myeloid leukaemia (CML) Treatment of Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph+ ALL)
• Drug interactions: Potentially hazardous interactions with other drugs Antibacterials: concentration reduced by rifampicin - avoid. Antipsychotics: avoid concomitant use with clozapine (increased risk of agranulocytosis).

Technology Process of Ponatinib

There total 33 articles about Ponatinib 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: 79.0%

3-ethynyl-4-methyl-N-(4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)benzamide (957147-18-1) + 3-bromo-imidazo[1,2-b]pyridazine (18087-73-5) → ponatinib (943319-70-8)

Guidance literature:

With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; caesium carbonate; tricyclohexylphosphine; In N,N-dimethyl-formamide; at 80 ℃; for 8h; Reagent/catalyst; Temperature; Inert atmosphere;

Reference yield: 54.0%

4-(4-methylpiperazin-1-ylmethyl)-3-trifluoromethylaniline (694499-26-8) + methyl 3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-benzoate → ponatinib (943319-70-8)

Guidance literature:

With potassium tert-butylate; In tetrahydrofuran; at 20 ℃; for 12h; Inert atmosphere;

DOI:10.1039/c8sc05618h

Reference yield:

4-(4-methylpiperazin-1-ylmethyl)-3-trifluoromethylaniline (694499-26-8) + C17H13N3O2*ClH → ponatinib (943319-70-8)

Guidance literature:

With potassium tert-butylate; In 2-methyltetrahydrofuran; at 13 - 23 ℃; for 3h;

upstream raw materials:

3-iodo-4-methyl-N-(4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl) phenyl)benzamide

3-ethynyl-imidazo[1,2-b]pyridazine

4-(4-methylpiperazin-1-ylmethyl)-3-trifluoromethylaniline

3-bromo-imidazo[1,2-b]pyridazine

Downstream raw materials:

Ponatinib Hydrochloride

Refernces

• 1、 Jin, Bo,Gallou, Fabrice,Reilly, John,Lipshutz, Bruce H.. "Ppm Pd-catalyzed, Cu-free Sonogashira couplings in water using commercially available catalyst precursors". . p. 3481 - 3485. Retrieved 2019/03/28.
• 2、 -. "PROCESSES FOR MAKING PONATINIB AND INTERMEDIATES THEREOF". . . Retrieved 2016/12/26.