Trademarks: Iclusig
Molecular Formula: C29H27F3N6O
CAS Registry Number: 943319-70-8
CAS Name: 3-(2-Imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]benzamide
Molecular Weight: 532.56
SMILES:CN1CCN(CC2=CC=C(NC(=O)C3=CC(C#CC4=CN=C5C=CC=NN45)=C(C)C=C3)C=C2C(F)(F)F)CC1
InChI Key: PHXJVRSECIGDHY-UHFFFAOYSA-N
InChI: InChI=1S/C29H27F3N6O/c1-20-5-6-22(16-21(20)8-10-25-18-33-27-4-3-11-34-38(25)27)28(39)35-24-9-7-23(26(17-24)29(30,31)32)19-37-14-12-36(2)13-15-37/h3-7,9,11,16-18H,12-15,19H2,1-2H3,(H,35,39)
Activity: Tyrosine Kinase Inhibitor; Protein Kinase Inhibitor; BCR-Abl Kinase Inhibitor; Oncolytic Drugs; Chronic Myelogenous Leukemia Therapy; CML Therapy; Antineoplastic Agents; Philadelphia Chromosome–positive (Ph+) Acute Lymphoblastic Leukemia Treatment; Acute Lymphoblastic Leukemia Therapy; ALL Therapy; T315I Mutant Bcr-abl Fusion Protein Inhibitor
Status: Launched 2012
Originator: ARIAD Pharmaceuticals
Ponatinib synthesis: WO2007075869A2
Ponatinib synthesis: WO2007075869A2 (intermediate)
Ponatinib synthesis: WO2014093583A2
Ponatinib synthesis: WO2014093583A2 (intermediate)
Orange book says for Ponatinib:
US8114874 Approval date (Dec 14, 2012) Expiration date (Dec 22, 2026)
References:
1. Zou, D.; et. al. Bicyclic heteroaryl compounds. WO2007075869A2
2. Huang, W.-S.; et. al. Discovery of 3-[2-(Imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-[4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl]benzamide (AP24534), a Potent, Orally Active Pan-Inhibitor of Breakpoint Cluster Region-Abelson (BCR-ABL) Kinase Including the T315I Gatekeeper Mutant. J Med Chem 2010, 53(12), 4701-4719.
3. Murray, C. K. et. al. Crystalline forms of 3-(imidazo[1,2-b] pyridazin-3-ylethynyl)-4-methyl-n-(4-[(4-methylpiperazin-1-yl) methyl]-3-(trifluoromethyl)phenyl)benzamide and its mono hydrochloride salt. WO2014093579A2
4. Murray, C. K. et. al. Synthetic methods for preparing 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-n-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl} benzamide mono hydrochloride, other salt forms of this compound and intermediates thereof. WO2014093583A2
5. Huang, W.-S.; et. al. Methods and compositions for treating cancer. WO2011053938A1 (activity)
6. Shamroe, C. L.; et. al. Ponatinib: A new tyrosine kinase inhibitor for the treatment of chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia. Ann Pharmacother 2013, 47(11), 1540-1546.
