Chemistry:Catequentinib
Catequentinib (INN; formerly anlotinib) is a pharmaceutical drug for the treatment of cancer. It is approved in China for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) in patients who have undergone progression or recurrence after at least two lines of systemic chemotherapy.[1] It is also approved in China as a second‑line treatment for advanced soft-tissue sarcoma.[2]
Catequentinib is a tyrosine kinase inhibitor that targets several different proteins including vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptors (PDGFR), and c-kit.[3]
Adverse effects include hypertension, fatigue, thyroid-stimulating hormone elevation, and hand-foot syndrome, among others.[4]
Synthesis
The synthesis of Catequentinib was recently reported:[5]
The reaction between 7-(Benzyloxy)-4-chloro-6-methoxyquinoline [286371-49-1] (1) & 4-Fluoro-5-hydroxy-2-methylindole [288385-88-6] (2) gives an intermediate [1210828-43-5]. Catalytic reduction resulted in debenzylation occurring to give [1210828-44-6] (3). Treatment of Cbz-1-Aminocyclopropylmethanol [103500-22-7] (4) with mesyl chloride gave [1058137-81-7] (5). Displacement of the leaving group by the unmasked aromatic alcohol resulted in ether formation, PC59805929 (6). The protecting group was then removed by catalytic reduction. Treatment with hydrogen chloride then completed the synthesis of the target molecule (7).
References
- ↑ "Anlotinib: First Global Approval". Drugs 78 (10): 1057–1062. July 2018. doi:10.1007/s40265-018-0939-x. PMID 29943374.
- ↑ "Anlotinib as a molecular targeted therapy for tumors". Oncology Letters 20 (2): 1001–1014. August 2020. doi:10.3892/ol.2020.11685. PMID 32724339.
- ↑ "Anlotinib: a novel multi-targeting tyrosine kinase inhibitor in clinical development". Journal of Hematology & Oncology 11 (1). September 2018. doi:10.1186/s13045-018-0664-7. PMID 30231931.
- ↑ "Research Progress on Mechanism and Management of Adverse Drug Reactions of Anlotinib". Drug Design, Development and Therapy 17: 3429–3437. 2023. doi:10.2147/DDDT.S426898. PMID 38024530.
- ↑ "Synthetic Approaches to New Drugs Approved during 2018". Journal of Medicinal Chemistry 63 (19): 10652–10704. 8 October 2020. doi:10.1021/acs.jmedchem.0c00345. https://pubs.acs.org/doi/10.1021/acs.jmedchem.0c00345.
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