Login Register Cart 0
Generic placeholder image

Recent Patents on Anti-Cancer Drug Discovery

Editor-in-Chief

ISSN (Print): 1574-8928
ISSN (Online): 2212-3970

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Recent Patents on the Development of c-Met Kinase Inhibitors

Author(s): Xiangming Xu and Lei Yao*

Volume 15, Issue 3, 2020

Page: [228 - 238] Pages: 11

DOI: 10.2174/1574892815666200630102344

Price: $65

Abstract

Background: Receptor Tyrosine Kinases (RTKs) play critical roles in a variety of cellular processes including growth, differentiation and angiogenesis, and in the development and progression of many types of cancer. Mesenchymal-Epithelial Transition Factor (c-Met) kinase is one of the types of RTKs and has become an attractive target for anti-tumor drug designing. c-Met inhibitors have a broad prospect in tumor prevention, chemotherapy, biotherapy, and especially in tumor resistance.

Objective: The purpose of this article is to review recent research progress of c-Met inhibitors reported in patents since 2015.

Methods: A comprehensive Scifinder and Web of Science literature review was conducted to identify all c-Met inhibitors published in patents since 2015.

Results: There are two kinds of c-Met inhibitors, one is from natural products, and the other one is of synthetic origin. Most of these c-Met inhibitors show potent in vivo and in vitro antitumor activities and have potential in the treatment of cancers.

Conclusion: c-Met kinase inhibitors have emerged as an exciting new drug class for the treatment of all kinds of cancers, especially the Non-Small Cell Lung Cancer (NSCLC) with tumor resistance. More studies should be conducted on natural products to find novel c-Met kinase inhibitors.

Keywords: Cancer, c-Met, inhibitors, patent, progress, receptor tyrosine kinases.

« Previous Next »
[1]
Butti R, Das S, Gunasekaran VP, Yadav AS, Kumar D, Kundu GC. Receptor tyrosine kinases (RTKs) in breast cancer: Signaling, therapeutic implications and challenges. Mol Cancer 2018; 17(1): 34.
[http://dx.doi.org/10.1186/s12943-018-0797-x] [PMID: 29455658]
[2]
Tomiguchi M, Yamamoto Y, Yamamoto-Ibusuki M, et al. Fibroblast growth factor receptor-1 protein expression is associated with prognosis in estrogen receptor-positive/human epidermal growth factor receptor-2-negative primary breast cancer. Cancer Sci 2016; 107(4): 491-8.
[http://dx.doi.org/10.1111/cas.12897] [PMID: 26801869]
[3]
Lemmon MA, Schlessinger J. Cell signaling by receptor tyrosine kinases. Cell 2010; 141(7): 1117-34.
[http://dx.doi.org/10.1016/j.cell.2010.06.011] [PMID: 20602996]
[4]
Baldacci S, Kherrouche Z, Cockenpot V, et al. MET amplification increases the metastatic spread of EGFR-mutated NSCLC. Lung Cancer 2018; 125: 57-67.
[http://dx.doi.org/10.1016/j.lungcan.2018.09.008] [PMID: 30429039]
[5]
Tsakonas G, Botling J, Micke P, et al. c-MET as a biomarker in patients with surgically resected non-small cell lung cancer. Lung Cancer 2019; 133: 69-74.
[http://dx.doi.org/10.1016/j.lungcan.2019.04.028] [PMID: 31200831]
[6]
Ma PC, Maulik G, Christensen J, Salgia R. c-Met: Structure, functions and potential for therapeutic inhibition. Cancer Metastasis Rev 2003; 22(4): 309-25.
[http://dx.doi.org/10.1023/A:1023768811842] [PMID: 12884908]
[7]
Xing W, Ai J, Jin S, et al. Enhancing the cellular anti-proliferation activity of pyridazinones as c-met inhibitors using docking analysis. Eur J Med Chem 2015; 95: 302-12.
[http://dx.doi.org/10.1016/j.ejmech.2015.03.041] [PMID: 25827399]
[8]
Parikh PK, Ghate MD. Recent advances in the discovery of small molecule c-Met kinase inhibitors. Eur J Med Chem 2018; 143: 1103-38.
[http://dx.doi.org/10.1016/j.ejmech.2017.08.044] [PMID: 29157685]
[9]
Toiyama Y, Miki C, Inoue Y, Okugawa Y, Tanaka K, Kusunoki M. Serum hepatocyte growth factor as a prognostic marker for stage II or III colorectal cancer patients. Int J Cancer 2009; 125(7): 1657-62.
[http://dx.doi.org/10.1002/ijc.24554] [PMID: 19569242]
[10]
Cappuzzo F, Marchetti A, Skokan M, et al. Increased MET gene copy number negatively affects survival of surgically resected non-small-cell lung cancer patients. J Clin Oncol 2009; 27(10): 1667-74.
[http://dx.doi.org/10.1200/JCO.2008.19.1635] [PMID: 19255323]
[11]
Wu ZX, Yang Y, Teng QX, et al. Tivantinib, A c-Met inhibitor in clinical trials, is susceptible to ABCG2-mediated drug resistance. Cancers (Basel) 2020; 12(1): 186.
[http://dx.doi.org/10.3390/cancers12010186] [PMID: 31940916]
[12]
Adjei AA, Sosman JA, Martell RE, et al. Efficacy in selected tumor types in a phase I study of the c-Met inhibitor ARQ 197 in combination with sorafenib. J Clinical Oncology 2011; 29(15_suppl): 3034.
[13]
Kim HJ, Yoon A, Ryu JY, et al. c-Met as a potential therapeutic target in ovarian clear cell carcinoma. Sci Rep 2016; 6: 38502.
[http://dx.doi.org/10.1038/srep38502] [PMID: 27917934]
[14]
Kim NA, Hong S, Kim KH, et al. New preclinical development of a c-Met inhibitor and its combined anti-tumor effect in c-Met-Amplified NSCLC. Pharmaceutics 2020; 12(2): 121.
[http://dx.doi.org/10.3390/pharmaceutics12020121] [PMID: 32028611]
[15]
An S, Yu J, Xu T, Hao P. Application of dictamnine in preparation of c-Met inhibitor for treating cancer. CN110755435, 2020.
[16]
Aliebrahimi S, Kouhsari SM, Arab SS, Shadboorestan A, Ostad SN. Phytochemicals, withaferin A and carnosol, overcome pancreatic cancer stem cells as c-Met inhibitors. Biomed Pharmacother 2018; 106: 1527-36.
[http://dx.doi.org/10.1016/j.biopha.2018.07.055] [PMID: 30119228]
[17]
Al-Salama ZT, Keating GM. Cabozantinib: A review in advanced renal cell carcinoma. Drugs 2016; 76(18): 1771-8.
[http://dx.doi.org/10.1007/s40265-016-0661-5] [PMID: 27909994]
[18]
Sahu A, Prabhash K, Noronha V, Joshi A, Desai S. Crizotinib: A comprehensive review. South Asian J Cancer 2013; 2(2): 91-7.
[http://dx.doi.org/10.4103/2278-330X.110506] [PMID: 24455567]
[19]
Duan M, Liu J, Tian S, Deng W, Yan C, Zhao L. Preparation of the multi-substituted pyridone derivatives and medical applications. WO2020042618, 2020.
[20]
Duan M, Liu J, Tian S, Dai Q, Xiong Y. Polysubstituted pyridonederivative useful in treatment of cancer and its preparation. WO2019080723, 2019.
[21]
Xu X, Li G, Ding C- Z, et al. Pyridone compound as c-Met inhibitor. WO2018077227, 2018.
[22]
Xu X, Li G, Yao T, Wang K, Hu L, Ding CZ. Crystal form of c-Met inhibitor and salt form thereof and preparation method therefor. WO2019206268, 2019.
[23]
Srivastava SK, Jha A, Agarwal SK, Mukherjee R, Burman AC. Synthesis and structure-activity relationships of potent antitumor active quinoline and naphthyridine derivatives. Anticancer Agents Med Chem 2007; 7(6): 685-709.
[http://dx.doi.org/10.2174/187152007784111313] [PMID: 18045063]
[24]
Davare MA, Saborowski A, Eide CA, Tognon C, Smith RL, Elferich J, et al. Foretinib is a potent ROS1 inhibitor. Proc Natl Acad Sci USA 2013; 110(48): 19519-24.
[http://dx.doi.org/10.1073/pnas.1319583110] [PMID: 24218589]
[25]
Qi XS, Guo XZ, Han GH, Li HY, Chen J. MET inhibitors for treatment of advanced hepatocellular carcinoma: A review. World J Gastroenterol 2015; 21(18): 5445-53.
[http://dx.doi.org/10.3748/wjg.v21.i18.5445] [PMID: 25987766]
[26]
Chen G. Compounds as c-Met kinase inhibitors. WO2012034055, 2012.
[27]
Gong F, Huang T, Zang H, Zhang S, Zhao R, Liu F. Preparation of N-[4-[[7-[[1-(cyclopentylamino)cyclopropyl]methoxy]-6- methoxy-4-quinolinyl oxy]-3-fluorophenyl]-N'-(4-fluorophenyl)-1,1-cyclopropanedicarboxamide crystal as c-Met kinase inhibitor for treatment of cancer. WO2019166012, 2019.
[28]
Zhang Q, Yu S, Wang Z, et al. Dioxazoline compound, preparation method therefor, and uses thereof. WO2019154133, 2019.
[29]
Zhang Q, Zhang H, Yang L, et al. Dioxanoquinazoline, dioxanoquinazoline-type compound, preparation method and application. WO2018153293, 2018.
[30]
Nan X, Li HJ, Fang SB, Li QY, Wu YC. Structure-based discovery of novel 4-(2-fluorophenoxy)quinoline derivatives as c-Met inhibitors using isocyanide-involved multicomponent reactions. Eur J Med Chem 2020; 193: 112241.
[http://dx.doi.org/10.1016/j.ejmech.2020.112241] [PMID: 32200199]
[31]
Zhang QW, Ye ZD, Shen C, Tie HX, Wang L, Shi L. Synthesis of novel 6,7-dimethoxy-4-anilinoquinolines as potent c-Met inhibitors. J Enzyme Inhib Med Chem 2019; 34(1): 124-33.
[http://dx.doi.org/10.1080/14756366.2018.1533822] [PMID: 30422010]
[32]
Zhao Z, Wang H, Wu C. [1,2,4] triazol [4,3-a] pyridine derivate preparation method therefor or medical application thereof. WO2014180182, 2014.
[33]
Li X, Zhang L, Sun Q, Lv A. Crystalline free base of C-MET inhibitor or crystalline acid salts, preparation methods and application. WO2016015653, 2016.
[34]
Yang B, Zhu Q, Pan B. Method for preparing c-Met tyrosine kinase inhibitor. CN106883250, 2017.
[35]
Yang B, Zhu Q, Pan B. Method for preparing c-Met tyrosine kinase inhibitor. WO2017101885, 2017.
[36]
Brown N. Bioisosteres in Medicinal Chemistry. 1st ed. Wiley-VCH. 2012
[http://dx.doi.org/10.1002/9783527654307]
[37]
Zhang Y, Chen Z, Wang Y, et al. Preparation of the azaindole derivative and their application as the c-Met inhibitor for the treatment of cancer. WO2020015744, 2020.
[38]
Hinklin RJ, Allen S, Barbour P, et al. Pyrazolo[3,4-b]pyridine compounds as inhibitors of TAM and MET kinases and their preparation. WO2020047184, 2020.
[39]
Zheng P, Zhu W, Tang Q, et al. Preparation of antitumor pyrrolopyrimidines. CN107383016, 2017.
[40]
Zhu W, Zheng P, Wang L, et al. Thienopyrimidine compound containing heteroaryl amide structure useful in treatment of cancer and its preparation. CN107253964, 2017.
[41]
Wang L, Liu X, Duan Y, et al. Discovery of novel pyrrolopyrimidine/pyrazolopyrimidine derivatives bearing 1,2,3-triazole moiety as c-Met kinase inhibitors. Chem Biol Drug Des 2018; 92(1): 1301-14.
[http://dx.doi.org/10.1111/cbdd.13192] [PMID: 29575727]
[42]
Li J, Gu W, Bi X, et al. Design, synthesis, and biological evaluation of thieno[2,3-d]pyrimidine derivatives as novel dual c-Met and VEGFR-2 kinase inhibitors. Bioorg Med Chem 2017; 25(24): 6674-9.
[http://dx.doi.org/10.1016/j.bmc.2017.11.010] [PMID: 29146452]
[43]
Zhao G, Zhao Y, Hu Y. Preparation of the indole-based small molecule C-MET inhibitor applied to treatment of cancers. CN107311983, 2017.
[44]
Zhao G, Hou Y, Zhao Y. Method for preparing indole type c-Met inhibitor. CN107382968, 2017.
[45]
Tang Q, Zheng P, Zhu W, et al. 1-Aryl-4-oxy-1,4-dihydroquinoline structure of pyridine and heterocyclic compound, preparation method and its application. CN108948014, 2018.
[46]
Sharma S, Zeng JY, Zhuang CM, et al. Small-molecule inhibitor BMS-777607 induces breast cancer cell polyploidy with increased resistance to cytotoxic chemotherapy agents. Mol Cancer Ther 2013; 12(5): 725-36.
[http://dx.doi.org/10.1158/1535-7163.MCT-12-1079] [PMID: 23468529]
[47]
Li X, Li D, Hong R. Preparation of c-Met inhibitor as anti-cancer drug. CN110218191, 2019.
[48]
Liu L, Siegmund A, Xi N, et al. Discovery of a potent, selective, and orally bioavailable c-Met inhibitor: 1-(2-Hydroxy-2-methylpropyl)-N-(5-(7-methoxyquinolin-4-yloxy)pyridin-2-yl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (AMG 458). J Med Chem 2008; 51(13): 3688-91.
[http://dx.doi.org/10.1021/jm800401t] [PMID: 18553959]
[49]
Huang W, Qian H, Gu W. Preparation of the 2,4-disubstituted pyridine and their medicine application for the treatment of cancer. CN108069938, 2018.
[50]
Li Q, Hu L, Dong H, et al. 3-(4-Fluorophenyl pyrimidone)-5-carboxamide derivative useful in treatment of cancer and its preparation. CN106543145, 2017.
[51]
Li Y, Geng M, Cui H, Ai J, Zhang W, Peng X. Quinolinones compound, preparation method, and use thereof. CN106146464, 2016.
[52]
Zagni C, Floresta G, Monciino G, Rescifina A. The search for potent, small-molecule HDACIs in cancer treatment: A decade after vorinostat. Med Res Rev 2017; 37(6): 1373-428.
[http://dx.doi.org/10.1002/med.21437] [PMID: 28181261]
[53]
Unknown. c-Met/HDAC double-target inhibitor based on crizotinib structure and synthesis method for antitumor drug. CN110003181, 2019.
[54]
Unknown. c-Met/HDAC double-target inhibitor, its synthesis method and application in preparing antitumor drugs. CN110128411, 2019.
[55]
Unknown. Novel c-Met/HDAC dual-target inhibitor and its synthesis method for antitumor drug preparation. CN110016013, 2019.
[56]
Cai P, Wang B. Preparation of 2,4-disubstituted triazole compounds with ALK and c-Met inhibition activities. CN105348265, 2016.
[57]
Xiong H, Cheng J, Zhang J, et al. Design, synthesis, and biological evaluation of pyridineamide derivatives containing a 1,2,3-triazole fragment as type II c-Met inhibitors. Molecules 2019; 25(1): 10.
[http://dx.doi.org/10.3390/molecules25010010] [PMID: 31861448]
[58]
Wang L, Gao M, Tong M, et al. Pharmacologic characterization of CT-711, a novel dual inhibitor of ALK and c-Met. Am J Cancer Res 2018; 8(8): 1541-50.
[PMID: 30210922]
[59]
Hao H, Huang X, Tam A, Kasibhatla S. Combination cancer therapy. WO2016016822, 2016.
[60]
Ren G, Yi D, Chen J. A crystal form of triazolopyrazine derivative and preparation method. CN105503906, 2016.
[61]
Ren G, Yi D, Chen J. B crystal form of savolitinib. CN105503905, 2016.
[62]
Yu J, Hao Y, Zhang J, et al. Salt of quinolone compound, polymorphs thereof, preparation method therefor, composition, and applications. WO2017114452, 2017.
[63]
Yu J, Guo L, Zhao F, et al. Quinoline-series compound, its preparation method, and pharmaceutical application. CN104109166, 2014.
[64]
Wu B, Shao S, Liu J. Compound containing the pharmaceutical composition and its application. CN108276418, 2018.
[65]
Guo Y, Peng X, Ji Y, et al. Synthesis of triazolotriazine derivatives as c-Met inhibitors. Mol Divers 2020.
[http://dx.doi.org/10.1007/s11030-020-10067-5] [PMID: 32157572]
[66]
Kim SC, Boggu PR, Yu HN, et al. Synthesis and biological evaluation of quinoxaline derivatives as specific c-Met kinase inhibitors. Bioorg Med Chem Lett 2020; 30(13): 127189.
[http://dx.doi.org/10.1016/j.bmcl.2020.127189] [PMID: 32371098]
[67]
Liang JW, Li SL, Wang S, Li WQ, Meng FH. Synthesis and biological evaluation of novel (E)-N′-benzylidene hydrazides as novel c-Met inhibitors through fragment based virtual screening. J Enzyme Inhib Med Chem 2020; 35(1): 468-77.
[http://dx.doi.org/10.1080/14756366.2019.1702655] [PMID: 31902266]
[68]
Frigault MM. Use of c-Met inhibitors to treat cancers harbouring met mutations. WO2018055029, 2018.
[69]
Shim SH, Lee J, Jung SY, et al. Combination therapy of c-Met-associated cancers using c-Met inhibitors and IGF-1 receptor inhibitors. US20160144027, 2016.
[70]
Aftab DT, Lamb P. Drug combinations to treat multiple myeloma. WO2016022697, 2016.
[71]
Zou Y, Ma D, Wang Y. The PROTAC technology in drug development. Cell Biochem Funct 2019; 37(1): 21-30.
[http://dx.doi.org/10.1002/cbf.3369] [PMID: 30604499]
[72]
Sun ZG, Yang YA, Zhang ZG, Zhu HL. Optimization techniques for novel c-Met kinase inhibitors. Expert Opin Drug Discov 2019; 14(1): 59-69.
[http://dx.doi.org/10.1080/17460441.2019.1551355] [PMID: 30518273]
[73]
Xu H, Wang M, Wu F, Zhuo L, Huang W, She N. Discovery of N-substituted-3-phenyl-1,6-naphthyridinone derivatives bearing quinoline moiety as selective type II c-Met kinase inhibitors against VEGFR-2. Bioorg Med Chem 2020; 28(12): 115555.
[http://dx.doi.org/10.1016/j.bmc.2020.115555] [PMID: 32503697]
[74]
Zhang B, Liu X, Xiong H, Zhang Q, Sun X, Yang Z, et al. Discovery of [1,2,4]triazolo[4,3-a]pyrazine derivatives bearing 4-oxo-pyridazinone moiety as potential c-Met kinase inhibitors. New J Chem 2020; 21.
[http://dx.doi.org/10.1039/D0NJ00575D]
[75]
Tang Q, Wang L, Tu Y, et al. Discovery of novel pyrrolo[2,3-b]pyridine derivatives bearing 1,2,3-triazole moiety as c-Met kinase inhibitors. Bioorg Med Chem Lett 2016; 26(7): 1680-4.
[http://dx.doi.org/10.1016/j.bmcl.2016.02.059] [PMID: 26923692]
[76]
Liu J, Gong Y, Shi J, et al. Design, synthesis and biological evaluation of novel N-[4-(2-fluorophenoxy)pyridin-2-yl]cyclopropanecarboxamide derivatives as potential c-Met kinase inhibitors. Eur J Med Chem 2020; 194: 112244.
[http://dx.doi.org/10.1016/j.ejmech.2020.112244] [PMID: 32224380]
[77]
Fan Y, Ding H, Kim D, et al. Antitumor activity of DFX117 by dual inhibition of c-Met and PI3Ka in non-small cell lung cancer. Cancers (Basel) 2019; 11(5): 627.
[http://dx.doi.org/10.3390/cancers11050627]
[78]
Lv PC, Yang YS, Wang ZC. Recent progress in the development of small molecule c-Met inhibitors. Curr Top Med Chem 2019; 19(15): 1276-88.
[http://dx.doi.org/10.2174/1568026619666190712205353] [PMID: 31526339]
[79]
Zhang Z, Chen Y, Wu H, et al. Design, synthesis, and biological evaluation of novel 2-amino-4-phenylthiazole derivatives as c-Met inhibitors. Youji Huaxue 2018; 38(10): 2648-56.
[http://dx.doi.org/10.6023/cjoc201803041]

Rights & Permissions Print Cite
Article Metrics
44
1
© 2024 Bentham Science Publishers | Privacy Policy