3,180
Views
0
CrossRef citations to date
0
Altmetric
Research Paper

6-Amino-2,4,5-trimethylpyridin-3-ol and 2-amino-4,6-dimethylpyrimidin-5-ol derivatives as selective fibroblast growth factor receptor 4 inhibitors: design, synthesis, molecular docking, and anti-hepatocellular carcinoma efficacy evaluation

, , , , , , ORCID Icon & ORCID Icon show all
Pages 844-856 | Received 20 Dec 2021, Accepted 25 Feb 2022, Published online: 17 Mar 2022

References

  • Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394–424.
  • Ganten TM, Stauber RE, Schott E, et al. Sorafenib in patients with hepatocellular carcinoma-results of the observational INSIGHT study. Clin Cancer Res 2017;23:5720–8.
  • Li D, Sedano S, Allen R, et al. Current treatment landscape for advanced hepatocellular carcinoma: patient outcomes and the impact on quality of life. Cancers (Basel) 2019;11:841.
  • Zappasodi R, Merghoub T, Wolchok JD. Emerging concepts for immune checkpoint blockade-based combination therapies. Cancer Cell 2018;33:581–98.
  • Partanen J, Mäkelä TP, Eerola E, et al. FGFR-4, a novel acidic fibroblast growth factor receptor with a distinct expression pattern. Embo J 1991;10:1347–54.
  • Prieto-Dominguez N, Shull AY, Teng Y. Making way for suppressing the FGF19/FGFR4 axis in cancer. Future Med Chem 2018;10:2457–70.
  • Huang X, Gollin SM, Raja S, Godfrey TE. High-resolution mapping of the 11q13 amplicon and identification of a gene, TAOS1 that is amplified and overexpressed in oral cancer cells. Proc Natl Acad Sci U S A 2002;99:11369–174.
  • Sawey ET, Chanrion M, Cai C, et al. Identification of a therapeutic strategy targeting amplified FGF19 in liver cancer by Oncogenomic screening. Cancer Cell 2011;19:347–58.
  • Tiong KH, Tan BS, Choo HL, et al. Fibroblast growth factor receptor 4 (FGFR4) and fibroblast growth factor 19 (FGF19) autocrine enhance breast cancer cells survival. Oncotarget 2016;7:57633–50.
  • Zhang X, Kong M, Zhang Z, et al. FGF19 genetic amplification as a potential therapeutic target in lung squamous cell carcinomas. Thorac Cancer 2017;8:655–65.
  • Ho HK, Pok S, Streit S, et al. Fibroblast growth factor receptor 4 regulates proliferation, anti-apoptosis and alpha-fetoprotein secretion during hepatocellular carcinoma progression and represents a potential target for therapeutic intervention. J Hepatol 2009;50:118–27.
  • Penault-Llorca F, Bertucci F, Adélaïde J, et al. Expression of FGF and FGF receptor genes in human breast cancer. Int J Cancer 1995;61:170–6.
  • Koole K, van Kempen PM, van Bockel LW, et al. fgfr4 is a potential predictive biomarker in oral and oropharyngeal squamous cell carcinoma. Pathobiology 2015;82:280–9.
  • Helsten T, Elkin S, Arthur E, et al. The FGFR landscape in cancer: analysis of 4,853 tumors by next-generation sequencing. Clin Cancer Res 2016;22:259–67.
  • Gowardhan B, Douglas DA, Mathers ME, et al. Evaluation of the fibroblast growth factor system as a potential target for therapy in human prostate cancer. Br J Cancer 2005;92:320–7.
  • Tang S, Hao Y, Yuan Y, et al. Role of fibroblast growth factor receptor 4 in cancer. Cancer Sci 2018;109:3024–31.
  • Liu H, Niu D, Tham Sjin RT, et al. Discovery of selective, covalent FGFR4 inhibitors with antitumor activity in models of hepatocellular carcinoma. ACS Med Chem Lett 2020;11:1899–904.
  • Joshi JJ, Coffey H, Corcoran E, et al. H3B-6527 is a potent and selective inhibitor of FGFR4 in FGF19-driven hepatocellular carcinoma. Cancer Res 2017;77:6999–7013.
  • Guagnano V, Furet P, Spanka C, et al. Discovery of 3-(2,6-dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-urea (NVP-BGJ398), a potent and selective inhibitor of the fibroblast growth factor receptor family of receptor tyrosine kinase. J Med Chem 2011;54:7066–83.
  • Hagel M, Miduturu C, Sheets M, et al. First selective small molecule inhibitor of fgfr4 for the treatment of hepatocellular carcinomas with an activated FGFR4 signaling pathway. Cancer Discov 2015;5:424–37.
  • Reynolds D, Hao MH, Wang J, Prajapati S, Satoh T, Selvaraj A. Eisai R&D Management Co., LTD. FGFR4 inhibitors. WO2016164703A1. 2016 Oct 13.
  • Wang Y, Chen Z, Dai M, et al. Discovery and optimization of selective FGFR4 inhibitors via scaffold hopping. Bioorg Med Chem Lett 2017;27:2420–3.
  • Mo C, Zhang Z, Guise CP, et al. 2-aminopyrimidine derivatives as new selective fibroblast growth factor receptor 4 (FGFR4) inhibitors. ACS Med Chem Lett 2017;8:543–8.
  • Weiss A, Adler F, Buhles A, et al. Graus porta D. FGF401, a first-in-class highly selective and potent FGFR4 inhibitor for the treatment of FGF19-driven hepatocellular cancer. Mol Cancer Ther 2019;18:2194–206.
  • Kim RD, Sarker D, Meyer T, et al. First-in-human phase I study of fisogatinib (BLU-554) validates aberrant FGF19 signaling as a driver event in hepatocellular carcinoma. Cancer Discov 2019;9:1696–707.
  • Rezende Miranda R, Fu Y, Chen X, et al. Development of a potent and specific FGFR4 inhibitor for the treatment of hepatocellular carcinoma. J Med Chem 2020;63:11484–97.
  • Packer LM, Pollock PM. Paralog-specific kinase inhibition of FGFR4: adding to the arsenal of anti-FGFR agents. Cancer Discov 2015;5:355–7.
  • Awasthi BP, Chaudhary P, Guragain D, et al. Synthesis and anti-hepatocellular carcinoma activity of aminopyridinol-sorafenib hybrids. J Enzyme Inhib Med Chem 2021;36:1884–97.
  • Karmacharya U, Guragain D, Chaudhary P, et al. Novel pyridine bioisostere of cabozantinib as a potent c-met kinase inhibitor: synthesis and anti-tumor activity against hepatocellular carcinoma. Int J Mol Sci 2021;22:9685.
  • Patani GA, LaVoie EJ. Bioisosterism: a rational approach in drug design. Chem Rev 1996;96:3147–76.
  • Lima LM, Barreiro EJ. Bioisosterism: a useful strategy for molecular modification and drug design. Curr Med Chem 2005;12:23–49.
  • Zeng D, Mi Q, Sun H, Wang H. A convenient synthesis of 14C-labelled resveratrol. J Label Compd Radiopharm 2004;47:167–74.
  • Kim DG, Kang Y, Lee H, et al. 6-Amino-2,4,5-trimethylpyridin-3-ols: a new general synthetic route and antiangiogenic activity. Eur J Med Chem 2014;78:126–39.
  • Dornow A, Hell H. Syntheses of nitrogen-containing heterocycles. XXIII. The preparation of 5-acetyloxazoles and their conversion to 5-hydroxypyrimidines. Chem Ber 1960;93:1998–2001.
  • Glišić BĐ, Hoffmann M, Warżajtis B, et al. Selectivity of the complexation reactions of four regioisomeric methylcamphorquinoxaline ligands with gold(III): X-ray, NMR and DFT investigations. Polyhedron 2016;105:137–49.
  • Garst ME, Dolby LJ, Esfandiari S, Mackenzie VR, Avey AA, Muchmore DC, Cooper GK, Malone TC. Allergan, Inc. Process for preparing isomerically pure prodrugs of proton pump inhibitors such as omeprazole and pantoprazole. US20050038076. 2005 Feb 17.
  • Lin X, Yosaatmadja Y, Kalyukina M, et al. Rotational freedom, steric hindrance, and protein dynamics explain BLU554 selectivity for the hinge cysteine of FGFR4. ACS Med Chem Lett 2019;10:1180–6.
  • Guagnano V, Kauffmann A, Wöhrle S, et al. Graus-Porta D. FGFR genetic alterations predict for sensitivity to NVP-BGJ398, a selective pan-FGFR inhibitor. Cancer Discov 2012;2:1118–33.
  • Zhao H, Lv F, Liang G, et al. FGF19 promotes epithelial-mesenchymal transition in hepatocellular carcinoma cells by modulating the GSK3β/β- catenin signaling cascade via FGFR4 activation. Oncotarget 2016;7:13575–86.
  • Kanzaki H, Chiba T, Ao J, et al. The impact of FGF19/FGFR4 signaling inhibition in antitumor activity of multi-kinase inhibitors in hepatocellular carcinoma. Sci Rep 2021;11:5303.
  • Stroganov OV, Novikov FN, Stroylov VS, et al. Lead finder: an approach to improve accuracy of protein-ligand docking, binding energy estimation, and virtual screening. J Chem Inf Model 2008;48:2371–85.