Catequentinib

Catequentinib
Clinical data
Trade names	Focus V
Other names	Anlotinib; AL3818; AL-3818
Identifiers
	IUPAC name 1-[[4-[(4-Fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxyquinolin-7-yl]oxymethyl]cyclopropan-1-amine;
CAS Number	1058156-90-3;
PubChem CID	25017411;
IUPHAR/BPS	9601;
DrugBank	DB11885;
ChemSpider	45743493;
UNII	GKF8S4C432;
KEGG	D12526;
ChEMBL	ChEMBL4303201;
Chemical and physical data
Formula	C23H22FN3O3
Molar mass	407.445 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC1=CC2=C(N1)C=CC(=C2F)OC3=C4C=C(C(=CC4=NC=C3)OCC5(CC5)N)OC;
	InChI InChI=InChI=1S/C23H22FN3O3/c1-13-9-15-16(27-13)3-4-19(22(15)24)30-18-5-8-26-17-11-21(20(28-2)10-14(17)18)29-12-23(25)6-7-23/h3-5,8-11,27H,6-7,12,25H2,1-2H3; Key:KSMZEXLVHXZPEF-UHFFFAOYSA-N;

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

^ Syed YY (July 2018). "Anlotinib: First Global Approval". Drugs. 78 (10): 1057–1062. doi:10.1007/s40265-018-0939-x. PMID 29943374.
^ Gao Y, Liu P, Shi R (August 2020). "Anlotinib as a molecular targeted therapy for tumors". Oncology Letters. 20 (2): 1001–1014. doi:10.3892/ol.2020.11685. PMC 7377159. PMID 32724339.
^ Shen G, Zheng F, Ren D, Du F, Dong Q, Wang Z, et al. (September 2018). "Anlotinib: a novel multi-targeting tyrosine kinase inhibitor in clinical development". Journal of Hematology & Oncology. 11 (1) 120. doi:10.1186/s13045-018-0664-7. PMC 6146601. PMID 30231931.
^ Li S, Wang H (2023). "Research Progress on Mechanism and Management of Adverse Drug Reactions of Anlotinib". Drug Design, Development and Therapy. 17: 3429–3437. doi:10.2147/DDDT.S426898. PMC 10657757. PMID 38024530.
^ Flick, A. C., Leverett, C. A., Ding, H. X., McInturff, E., Fink, S. J., Helal, C. J., et al. (8 October 2020). "Synthetic Approaches to New Drugs Approved during 2018". Journal of Medicinal Chemistry. 63 (19): 10652–10704. doi:10.1021/acs.jmedchem.0c00345.

[1] Syed YY (July 2018). "Anlotinib: First Global Approval". Drugs. 78 (10): 1057–1062. doi:10.1007/s40265-018-0939-x. PMID 29943374.

[2] Gao Y, Liu P, Shi R (August 2020). "Anlotinib as a molecular targeted therapy for tumors". Oncology Letters. 20 (2): 1001–1014. doi:10.3892/ol.2020.11685. PMC 7377159. PMID 32724339.

[3] Shen G, Zheng F, Ren D, Du F, Dong Q, Wang Z, et al. (September 2018). "Anlotinib: a novel multi-targeting tyrosine kinase inhibitor in clinical development". Journal of Hematology & Oncology. 11 (1) 120. doi:10.1186/s13045-018-0664-7. PMC 6146601. PMID 30231931.

[4] Li S, Wang H (2023). "Research Progress on Mechanism and Management of Adverse Drug Reactions of Anlotinib". Drug Design, Development and Therapy. 17: 3429–3437. doi:10.2147/DDDT.S426898. PMC 10657757. PMID 38024530.

[5] Flick, A. C., Leverett, C. A., Ding, H. X., McInturff, E., Fink, S. J., Helal, C. J., et al. (8 October 2020). "Synthetic Approaches to New Drugs Approved during 2018". Journal of Medicinal Chemistry. 63 (19): 10652–10704. doi:10.1021/acs.jmedchem.0c00345.

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