Ponatinib

CAT#: H202320

CAS#: 943319-70-8

Description: Ponatinib is an orally bioavailable multitargeted receptor tyrosine kinase (RTK) inhibitor with potential antiangiogenic and antineoplastic activities. Multitargeted tyrosine kinase inhibitor AP24534 inhibits unmutated and all mutated forms of Bcr-Abl, including T315I, the highly drug therapy-resistant missense mutation of Bcr-Abl. This agent also inhibits other tyrosine kinases including those associated with vascular endothelial growth factor receptors (VEGFRs) and fibroblast growth factor receptors (FGFRs); in addition, it inhibits the tyrosine kinase receptor TIE2 and FMS-related tyrosine kinase receptor-3 (Flt3).

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Synthetic Routes

Ponatinib - Synthetic Route 1

Ponatinib route01

Synthetic reference

Huang, Wei-Sheng; Metcalf, Chester A.; Sundaramoorthi, Raji; Wang, Yihan; Zou, Dong; Thomas, R. Mathew; Zhu, Xiaotian; Cai, Lisi; Wen, David; Liu, Shuangying; Romero, Jan; Qi, Jiwei; Chen, Ingrid; Banda, Geetha; Lentini, Scott P.; Das, Sasmita; Xu, Qihong; Keats, Jeff; Wang, Frank; Wardwell, Scott; Ning, Yaoyu; Snodgrass, Joseph T.; Broudy, Marc I.; Russian, Karin; Zhou, Tianjun; Commodore, Lois; Narasimhan, Narayana I.; Mohemmad, Qurish K.; Iuliucci, John; Rivera, Victor M.; Dalgarno, David C.; Sawyer, Tomi K.; Clackson, Tim; Shakespeare, William C. 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. Journal of Medicinal Chemistry. Volume 53. Issue 12. Pages 4701-4719. Journal. (2010).

Ponatinib - Synthetic Route 2

Ponatinib route02

Synthetic reference

Tian, Kun; Yue, Hongliang; Zhou, Changling; Dai, Juan; Chen, Haixia; Liu, Yan; Xu, Hao. Synthesis of ponatinib. Guangdong Huagong. Volume 40. Issue 12. Pages 24-25. Journal. (2013).

Ponatinib - Synthetic Route 3

Ponatinib route03

Synthetic reference

Jin, Bo; Gallou, Fabrice; Reilly, John; Lipshutz, Bruce H. ppm Pd-​catalyzed, Cu-​free Sonogashira couplings in water using commercially available catalyst precursors. Chemical Science. Volume 10. Issue 12. Pages 3481-3485. Journal; Online Computer File. (2019).

Ponatinib - Synthetic Route 4

Ponatinib route04

Synthetic reference

: Kovi, Ravishanker; Kannapan, Jayaraman; Thakor, Sanjay F.; Naik, Ashish; Bharatbhai, Dhakhada Chetana; Khichi, Kuldip Fatehlal; Shivnath, Sahebrao Patil. Processes for making ponatinib and intermediates thereof. Assignee Apicore US LLC, USA. WO 2016201203. (2016).

Ponatinib - Synthetic Route 5

Ponatinib route05

Synthetic reference

: Xu, Xuenong. Process for the preparation of Ponatinib. Assignee Suzhou Miracpharma Technology Co., Ltd., Peop. Rep. China. CN 103664960. (2014).

Ponatinib - Synthetic Route 6

Ponatinib route06

Synthetic reference

Kovi, Ravishanker; Kannapan, Jayaraman; Thakor, Sanjay F.; Patel, Rajesh A. Processes for making ponatinib and intermediates thereof. Assignee Apicore, LLC, USA. US 20140343282. (2014).

Ponatinib - Synthetic Route 7

Ponatinib route07

Synthetic reference

Wang, Yong; Zhao, Liwen; Chen, Hongyan; Zhang, Di; Xu, Xin; Zhang, Cang; Zhang, Hongxing. Process for the preparation of ponatinib useful in the treatment of chronic promyelocytic leukemia. Assignee Nanjing Sanhome Pharmaceutical Co., Ltd., Peop. Rep. China. CN 103664951. (2014).