{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T23:01:56Z","timestamp":1778626916894,"version":"3.51.4"},"reference-count":113,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T00:00:00Z","timestamp":1731456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia\/Minist\u00e9rio da Ci\u00eancia, Tecnologia e Ensino Superior (FCT\/MCTES)","doi-asserted-by":"publisher","award":["UIDB\/50006\/2020|UIDP\/50006\/2020"],"award-info":[{"award-number":["UIDB\/50006\/2020|UIDP\/50006\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia\/Minist\u00e9rio da Ci\u00eancia, Tecnologia e Ensino Superior (FCT\/MCTES)","doi-asserted-by":"publisher","award":["2022.02910.PTDC"],"award-info":[{"award-number":["2022.02910.PTDC"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia\/Minist\u00e9rio da Ci\u00eancia, Tecnologia e Ensino Superior (FCT\/MCTES)","doi-asserted-by":"publisher","award":["UIDB\/04565\/2020"],"award-info":[{"award-number":["UIDB\/04565\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia\/Minist\u00e9rio da Ci\u00eancia, Tecnologia e Ensino Superior (FCT\/MCTES)","doi-asserted-by":"publisher","award":["LA\/P\/0140\/2020"],"award-info":[{"award-number":["LA\/P\/0140\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia\/Minist\u00e9rio da Ci\u00eancia, Tecnologia e Ensino Superior (FCT\/MCTES)","doi-asserted-by":"publisher","award":["UIDB\/04585\/2020"],"award-info":[{"award-number":["UIDB\/04585\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia\/Minist\u00e9rio da Ci\u00eancia, Tecnologia e Ensino Superior (FCT\/MCTES)","doi-asserted-by":"publisher","award":["UIDB\/00313\/2020"],"award-info":[{"award-number":["UIDB\/00313\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Vascular endothelial growth factor receptor 2 (VEGFR-2) is a crucial mediator of angiogenesis, playing a pivotal role in both normal physiological processes and cancer progression. Tumors harness VEGFR-2 signaling to promote abnormal blood vessel growth, which is a key step in the metastasis process, making it a valuable target for anticancer drug development. While there are VEGFR-2 inhibitors approved for therapeutic use, they face challenges like drug resistance, off-target effects, and adverse side effects, limiting their effectiveness. The quest for new drug candidates with VEGFR-2 inhibitory activity often starts with the selection of key structural motifs present in molecules currently used in clinical practice, expanding the chemical space by generating novel derivatives bearing one or more of these moieties. This review provides an overview of recent advances in the development of novel VEGFR-2 inhibitors, focusing on the synthesis of new drug candidates with promising antiproliferative and VEGFR-2 inhibition activities, organizing them by relevant structural features.<\/jats:p>","DOI":"10.3390\/molecules29225341","type":"journal-article","created":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T06:23:16Z","timestamp":1731478996000},"page":"5341","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Targeting Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2): Latest Insights on Synthetic Strategies"],"prefix":"10.3390","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1697-7871","authenticated-orcid":false,"given":"Carolina S.","family":"Marques","sequence":"first","affiliation":[{"name":"LAQV-REQUIMTE, Institute for Research and Advanced Training, University of \u00c9vora, Rua Rom\u00e3o Ramalho, 59, 7000-641 Evora, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1455-7470","authenticated-orcid":false,"given":"Pedro","family":"Brand\u00e3o","sequence":"additional","affiliation":[{"name":"Egas Moniz Center for Interdisciplinary Research (CiiEM), Egas Moniz School of Health & Science, Campus Universit\u00e1tio, Quinta da Granja, Monte da Caparica, 2829-511 Caparica, Portugal"},{"name":"Centro de Qu\u00edmica de Coimbra, Institute of Molecular Sciences (CQC-IMS), Departamento de Qu\u00edmica, Faculdade de Ci\u00eancias e Tecnologia, University of Coimbra, 3004-535 Coimbra, Portugal"},{"name":"iBB-Institute for Bioengineering and Biosciences, Department of Bioengineering, Associate Laboratory i4HB\u2013Institute for Health and Bio-Economy, Instituto Superior T\u00e9cnico, University of Lisboa, Av. Rovisco Pais, 1049-001 Lisbon, Portugal"}]},{"given":"Anthony J.","family":"Burke","sequence":"additional","affiliation":[{"name":"Centro de Qu\u00edmica de Coimbra, Institute of Molecular Sciences (CQC-IMS), Departamento de Qu\u00edmica, Faculdade de Ci\u00eancias e Tecnologia, University of Coimbra, 3004-535 Coimbra, Portugal"},{"name":"Faculty of Pharmacy, University of Coimbra, P\u00f3lo das Ci\u00eancias da Sa\u00fade, 3000-548 Coimbra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Wang, X., Bove, A.M., Simone, G., and Ma, B. (2020). Molecular Bases of VEGFR-2-Mediated Physiological Function and Pathological Role. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.599281"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1158\/1078-0432.CCR-22-1366","article-title":"Molecular Mechanisms and Future Implications of VEGF\/VEGFR in Cancer Therapy","volume":"29","author":"Patel","year":"2023","journal-title":"Clin. Cancer Res."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Mabeta, P., and Steenkamp, V. (2022). The VEGF\/VEGFR Axis Revisited: Implications for Cancer Therapy. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232415585"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2540","DOI":"10.2174\/0929867327666200514082425","article-title":"Anti-angiogenic Agents: A Review on Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2) Inhibitors","volume":"28","author":"Kang","year":"2021","journal-title":"Curr. Med. Chem."},{"key":"ref_5","first-page":"50","article-title":"Tumor Angiogenesis and VEGFR-2: Mechanism, Pathways and Current Biological Therapeutic Interventions","volume":"22","author":"Altaf","year":"2021","journal-title":"Curr. Drug Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"100009","DOI":"10.1016\/j.medidd.2019.100009","article-title":"Vascular Endothelial Growth Factor Receptor (VEGFR-2)\/KDR Inhibitors: Medicinal Chemistry Perspective","volume":"2","author":"Siddharth","year":"2019","journal-title":"Med. Drug Discov."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Liu, X.-J., Zhao, H.-C., Hou, S.-J., Zhang, H.-J., Cheng, L., Yuan, S., Zhang, L.-R., Song, J., Zhang, S.-Y., and Chen, S.-W. (2023). Recent development of multi-target VEGFR-2 inhibitors for the cancer therapy. Bioorg. Chem., 133.","DOI":"10.1016\/j.bioorg.2023.106425"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1080\/14756366.2017.1334650","article-title":"VEGFR-2 inhibitors and apoptosis inducers: Synthesis and molecular design of new benzo[g]quinazolin bearing benzenesulfonamide moiety","volume":"32","author":"Ghorab","year":"2017","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Ballmer-Hofer, K. (2018). Vascular Endothelial Growth Factor, from Basic Research to Clinical Applications. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19123750"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Zhang, Q., Zheng, P., and Zhu, W. (2020). Research Progress of Small Molecule VEGFR\/c-Met Inhibitors as Anticancer Agents (2016\u2013Present). Molecules, 25.","DOI":"10.3390\/molecules25112666"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"S, V., Kajal, K., Mondal, S., Wahan, S.K., Das Kurmi, B., Das Gupta, G., and Patel, P. (2023). Novel VEGFR-2 Kinase Inhibitors as Anticancer Agents: A Review Focusing on SAR and Molecular Docking Studies (2016\u20132021). Chem. Biodivers., 20.","DOI":"10.1002\/cbdv.202200847"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1080\/13543776.2021.1935872","article-title":"An updated patent review of VEGFR-2 inhibitors (2017\u2013present)","volume":"31","author":"Farghaly","year":"2021","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1080\/14756366.2021.1901089","article-title":"Design, synthesis, anticancer evaluation, and molecular modelling studies of novel tolmetin derivatives as potential VEGFR-2 inhibitors and apoptosis inducers","volume":"36","author":"Kassab","year":"2021","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1002\/ardp.201500178","article-title":"Synthesis of Tolmetin Hydrazide\u2013Hydrazones and Discovery of a Potent Apoptosis Inducer in Colon Cancer Cells","volume":"348","author":"Orun","year":"2015","journal-title":"Arch. Pharm."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Fadaly, W.A.A., Elshaier, Y.A.M.M., Hassanein, E.H.M., and Abdellatif, K.R.A. (2020). New 1,2,4-triazole\/pyrazole hybrids linked to oxime moiety as nitric oxide donor celecoxib analogs: Synthesis, cyclooxygenase inhibition anti-inflammatory, ulcerogenicity, anti-proliferative activities, apoptosis, molecular modeling and nitric oxide release studies. Bioorg. Chem., 98.","DOI":"10.1016\/j.bioorg.2020.103752"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Dawood, D.H., Nossier, E.S., Ali, M.M., and Mahmoud, A.E. (2020). Synthesis and molecular docking study of new pyrazole derivatives as potent anti-breast cancer agents targeting VEGFR-2 kinase. Bioorg. Chem., 101.","DOI":"10.1016\/j.bioorg.2020.103916"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2100158","DOI":"10.1002\/ardp.202100158","article-title":"1,2,3-Triazole hybrids as anticancer agents: A review","volume":"355","author":"Alam","year":"2022","journal-title":"Arch. Pharm."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3269","DOI":"10.2174\/1871520622666220412133112","article-title":"Design and Development of Triazole Derivatives as Prospective Anticancer Agents: A Review","volume":"22","author":"Sachdeva","year":"2022","journal-title":"Anticancer Agents Med. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2962","DOI":"10.1016\/j.bmcl.2013.03.042","article-title":"Novel VEGFR-2 kinase inhibitor identified by the back-to-front approach","volume":"23","author":"Sanphanya","year":"2013","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Al-Hussain, S.A., Farghaly, T.A., Zaki, M.E.A., Abdulwahab, H.G., Al-Qurashi, N.T., and Muhammad, Z.A. (2020). Discovery of novel indolyl-1,2,4-triazole hybrids as potent vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitors with potential anti-renal cancer activity. Bioorg. Chem., 105.","DOI":"10.1016\/j.bioorg.2020.104330"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"10558","DOI":"10.1021\/acs.jmedchem.3c00721","article-title":"1,5-Diaryl-1,2,4-triazole Ureas as New SLC-0111 Analogues Endowed with Dual Carbonic Anhydrase and VEGFR-2 Inhibitory Activities","volume":"66","author":"Elsawi","year":"2023","journal-title":"J. Med. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Atta-Allah, S.R., AboulMagd, A.M., and Farag, P.S. (2021). Design, microwave assisted synthesis, and molecular modeling study of some new 1,3,4-thiadiazole derivatives as potent anticancer agents and potential VEGFR-2 inhibitors. Bioorg. Chem., 112.","DOI":"10.1016\/j.bioorg.2021.104923"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"136448","DOI":"10.1016\/j.molstruc.2023.136448","article-title":"Novel azole-urea hybrids as VEGFR-2 inhibitors: Synthesis, in vitro antiproliferative evaluation and in silico studies","volume":"1294","author":"Shirzad","year":"2023","journal-title":"J. Mol. Struct."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Sayed, A.M., Taher, F.A., Abdel-Samad, M.R.K., El-Gaby, M.S.A., El-Adl, K., and Saleh, N.M. (2021). Design, synthesis, molecular docking, in silico ADMET profile and anticancer evaluations of sulfonamide endowed with hydrazone-coupled derivatives as VEGFR-2 inhibitors. Bioorg. Chem., 108.","DOI":"10.1016\/j.bioorg.2021.104669"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"El-Adl, K., El-Helby, A.-G.A., Sakr, H., Eissa, I.H., El-Hddad, S.S.A., and Shoman, F.M.I.A. (2020). Design, synthesis, molecular docking and anticancer evaluations of 5-benzylidenethiazolidine-2,4-dione derivatives targeting VEGFR-2 enzyme. Bioorg. Chem., 102.","DOI":"10.1016\/j.bioorg.2020.104059"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"27801","DOI":"10.1039\/D3RA05689A","article-title":"Synthesis, biological evaluation and computer-aided discovery of new thiazolidine-2,4-dione derivatives as potential antitumor VEGFR-2 inhibitors","volume":"13","author":"Elkady","year":"2023","journal-title":"RSC Adv."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1903","DOI":"10.1080\/14756366.2022.2085693","article-title":"Design and synthesis of thiazolidine-2,4-diones hybrids with 1,2-dihydroquinolones and 2-oxindoles as potential VEGFR-2 inhibitors: In-vitro anticancer evaluation and in-silico studies","volume":"37","author":"Taghour","year":"2022","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.bioorg.2018.10.071","article-title":"Design, synthesis, biological evaluation and dynamics simulation of indazole derivatives with antiangiogenic and antiproliferative anticancer activity","volume":"82","author":"Elsayed","year":"2019","journal-title":"Bioorg. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.ejmech.2017.04.068","article-title":"Design, synthesis, molecular docking and cytotoxic evaluation of novel 2-furybenzimidazoles as VEGFR-2 inhibitors","volume":"136","author":"Abdullaziz","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Abdel-Mohsen, H.-T., Abdullaziz, M.A., El Kerdawy, A.M., Ragab, F.A.F., Flanagan, K.J., Mahmoud, A.E.E., Ali, M.M., El Diwani, H.I., and Senge, M.O. (2020). Targeting Receptor Tyrosine Kinase VEGFR-2 in Hepatocellular Cancer: Rational Design, Synthesis and Biological Evaluation of 1,2-Disubstituted Benzimidazoles. Molecules, 25.","DOI":"10.3390\/molecules25040770"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1002\/cmdc.201600224","article-title":"Discovery of a Nanomolar Multikinase Inhibitor (KST016366): A New Benzothiazole Derivative with Remarkable Broad-Spectrum Antiproliferative Activity","volume":"11","author":"Cho","year":"2016","journal-title":"Chem. Med. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1900178","DOI":"10.1002\/ardp.201900178","article-title":"Benzoxazole\/benzothiazole-derived VEGFR-2 inhibitors: Design, synthesis, molecular docking, and anticancer evaluations","volume":"352","author":"Sakr","year":"2019","journal-title":"Arch. Pharm."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1080\/14756366.2021.2015343","article-title":"New benzoxazole derivatives as potential VEGFR-2 inhibitors and apoptosis inducers: Design, synthesis, anti-proliferative evaluation, flowcytometric analysis, and in silico studies","volume":"37","author":"Elkady","year":"2022","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.ejmech.2019.06.054","article-title":"Design, synthesis and in vitro evaluation of 6-amide-2-aryl benzoxazole\/benzimidazole derivatives against tumor cells by inhibiting VEGFR-2 kinase","volume":"179","author":"Yuan","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"7222","DOI":"10.1080\/10408398.2021.1913091","article-title":"Natural products targeting into cancer hallmarks: An update on caffeine, theobromine, and (+)-catechin","volume":"62","author":"Dantas","year":"2022","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.4155\/fmc-2023-0089","article-title":"New theobromine derivatives inhibiting VEGFR-2: Design, synthesis, antiproliferative, docking and molecular dynamics simulations","volume":"15","author":"Mahdy","year":"2023","journal-title":"Future Med. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Eissa, I.H., Yousef, R.G., Elkady, H., Elkaeed, E.B., Alsfouk, A.A., Husein, D.Z., Ibrahim, I.M., Elhendawy, M.A., Godfrey, M., and Metwaly, A.M. (2023). Design, semi-synthesis, anti-cancer assessment, docking, MD simulation, and DFT studies of novel theobromine-based derivatives as VEGFR-2 inhibitors and apoptosis inducers. Comput. Biol. Chem., 107.","DOI":"10.1016\/j.compbiolchem.2023.107953"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"23285","DOI":"10.1039\/D3RA04007K","article-title":"Identification of new theobromine-based derivatives as potent VEGFR-2 inhibitors: Design, semi-synthesis, biological evaluation, and in silico studies","volume":"13","author":"Eissa","year":"2023","journal-title":"RSC Adv."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.ejmech.2019.02.050","article-title":"Design, synthesis and docking study of novel picolinamide derivatives as anticancer agents and VEGFR-2 inhibitors","volume":"168","author":"Zeidan","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1021\/ml500066m","article-title":"Discovery of Anilinopyrimidines as Dual Inhibitors of c-Met and VEGFR-2: Synthesis, SAR, and Cellular Activity","volume":"5","author":"Zhan","year":"2014","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.ejmech.2018.03.018","article-title":"Structure-activity relationships of 2, 4-disubstituted pyrimidines as dual ER\u03b1\/VEGFR-2 ligands with anti-breast cancer activity","volume":"150","author":"Luo","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"112457","DOI":"10.1016\/j.ejmech.2020.112457","article-title":"Exploration of carbamide derived pyrimidine-thioindole conjugates as potential VEGFR-2 inhibitors with anti-angiogenesis effect","volume":"200","author":"Sana","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"22122","DOI":"10.1039\/D3RA04182D","article-title":"Design, synthesis, in silico studies, and biological evaluation of novel pyrimidine-5-carbonitrile derivatives as potential anti-proliferative agents, VEGFR-2 inhibitors and apoptotic inducers","volume":"13","author":"Saleh","year":"2023","journal-title":"RSC Adv."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.ejmech.2019.06.063","article-title":"Novel potent substituted 4-amino-2-thiopyrimidines as dual VEGFR-2 and BRAF kinase inhibitors","volume":"179","author":"Omar","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1900089","DOI":"10.1002\/ardp.201900089","article-title":"New 2,4-disubstituted-2-thiopyrimidines as VEGFR-2 inhibitors: Design, synthesis, and biological evaluation","volume":"352","author":"Girgis","year":"2019","journal-title":"Arch. Pharm."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Aziz, M.A., Serya, R.A.T., Lasheen, D.S., Abdel-Aziz, A.K., Esmat, A., Mansour, A.M., Singab, A.N.B., and Abouzid, K.A.M. (2016). Discovery of Potent VEGFR-2 Inhibitors based on Furopyrimidine and Thienopyrimidne Scaffolds as Cancer Targeting Agents. Sci. Rep., 6.","DOI":"10.1038\/srep24460"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.bioorg.2018.10.008","article-title":"Design, synthesis and molecular modeling study of certain VEGFR-2 inhibitors based on thienopyrimidne scaffold as cancer targeting agents","volume":"83","author":"Ghith","year":"2019","journal-title":"Bioorg. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"El-Metwally, S.A., Abou-El-Regal, M.M., Eissa, I.H., Mehany, A.B.M., Mahdy, H.A., Elkady, H., Elwan, A., and Elkaeed, E.B. (2021). Discovery of thieno[2,3-d]pyrimidine-based derivatives as potent VEGFR-2 kinase inhibitors and anti-cancer agents. Bioorg. Chem., 112.","DOI":"10.1016\/j.bioorg.2021.104947"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"6497","DOI":"10.1016\/j.bmc.2015.08.010","article-title":"Synthesis, antiangiogenesis evaluation and molecular docking studies of 1-aryl-3-[(thieno[3,2-b]pyridin-7-ylthio)phenyl]ureas: Discovery of a new substitution pattern for type II VEGFR-2 Tyr kinase inhibitors","volume":"23","author":"Machado","year":"2015","journal-title":"Bioorg. Med. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2791","DOI":"10.1002\/jcb.25580","article-title":"Antiangiogenic 1-Aryl-3-[3-(thieno[3,2-b]pyridin-7-ylthio) phenyl]ureas Inhibit MCF-7 and MDA-MB-231 Human Breast Cancer Cell Lines Through PI3K\/Akt and MAPK\/Erk Pathways","volume":"117","author":"Machado","year":"2016","journal-title":"J. Cell. Biochem."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Soares, P., Costa, R., Froufe, H.J.C., Calhelha, R.C., Peixoto, D., Ferreira, I.C.F.R., Abreu, R.M.V., Soares, R., and Queiroz, M.-J.R.P. (2013). 1-Aryl-3-[4-(thieno[3,2-d]pyrimidin-4-yloxy)phenyl]ureas as VEGFR-2 Tyrosine Kinase Inhibitors: Synthesis, Biological Evaluation, and Molecular Modelling Studies. Biomed Res. Int., 2013.","DOI":"10.1155\/2013\/154856"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"El-Metwally, S.A., Abuelkhir, A.A., Elkady, H., Taghour, M.S., Ibrahim, I.M., Husein, D.Z., Alsfouk, A.A., Sultan, A., Ismail, A., and Elkhawaga, S.Y. (2023). In vitro and in silico evaluation of new thieno[2,3-d]pyrimidines as anti-cancer agents and apoptosis inducers targeting VEGFR-2. Comput. Biol. Chem., 106.","DOI":"10.1016\/j.compbiolchem.2023.107928"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"23365","DOI":"10.1039\/D3RA03128D","article-title":"Design, synthesis, anti-proliferative evaluation, docking, and MD simulation studies of new thieno[2,3-d]pyrimidines targeting VEGFR-2","volume":"13","author":"Elkady","year":"2023","journal-title":"RSC Adv."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1016\/j.ejmech.2018.09.050","article-title":"Exploration of novel pyrrolo[2,1-f][1,2,4]triazine derivatives with improved anticancer efficacy as dual inhibitors of c-Met\/VEGFR-2","volume":"158","author":"Shi","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.ejmech.2018.05.054","article-title":"Design, synthesis, biological evaluation and molecular modeling of novel 1H-pyrazolo[3,4-d]pyrimidine derivatives as BRAFV600E and VEGFR-2 dual inhibitors","volume":"155","author":"Wang","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"101712","DOI":"10.1016\/j.jscs.2023.101712","article-title":"Novel pyrrolo[2,3-d]pyrimidine derivatives as multi-kinase inhibitors with VEGFR-2 selectivity","volume":"27","author":"Alotaibi","year":"2023","journal-title":"J. Saudi Chem. Soc."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1080\/14756366.2020.1861606","article-title":"Novel piperazine\u2013chalcone hybrids and related pyrazoline analogues targeting VEGFR-2 kinase; design, synthesis, molecular docking studies, and anticancer evaluation","volume":"36","author":"Ahmed","year":"2021","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"115626","DOI":"10.1016\/j.ejmech.2023.115626","article-title":"Quinazoline-based VEGFR-2 inhibitors as potential anti-angiogenic agents: A contemporary perspective of SAR and molecular docking studies","volume":"259","author":"Moradi","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"4367","DOI":"10.1039\/c3ob40368h","article-title":"Novel 5-anilinoquinazoline-8-nitro derivatives as inhibitors of VEGFR-2 tyrosine kinase: Synthesis, biological evaluation and molecular docking","volume":"11","author":"Xi","year":"2013","journal-title":"Org. Biomol. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejmech.2013.10.058","article-title":"Novel 2-chloro-4-anilino-quinazoline derivatives as EGFR and VEGFR-2 dual inhibitors","volume":"71","author":"Lima","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"4735","DOI":"10.1016\/j.bmc.2014.07.008","article-title":"Discovery of quinazolin-4-amines bearing benzimidazole fragments as dual inhibitors of c-Met and VEGFR-2","volume":"22","author":"Shi","year":"2014","journal-title":"Bioorg. Med. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.ejmech.2015.12.032","article-title":"Design and discovery of 4-anilinoquinazoline-acylamino derivatives as EGFR and VEGFR-2 dual TK inhibitors","volume":"109","author":"Zhang","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.ejmech.2016.09.039","article-title":"Design and discovery of 4-anilinoquinazoline-urea derivatives as dual TK inhibitors of EGFR and VEGFR-2","volume":"125","author":"Zhang","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"111552","DOI":"10.1016\/j.ejmech.2019.07.055","article-title":"Design, synthesis and biological evaluation of novel 4-anilinoquinazoline derivatives as hypoxia-selective EGFR and VEGFR-2 dual inhibitors","volume":"181","author":"Wei","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.ejmech.2014.04.007","article-title":"Inhibition of tumor cell growth and angiogenesis by 7-Aminoalkoxy-4-aryloxy-quinazoline ureas, a novel series of multi-tyrosine kinase inhibitors","volume":"79","author":"Ravez","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1021\/acs.jmedchem.7b01091","article-title":"Discovery of Novel Potent VEGFR-2 Inhibitors Exerting Significant Antiproliferative Activity against Cancer Cell Lines","volume":"61","author":"Zhang","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Hou, F., Yao, Y., Wei, Y., Wang, Y., Cao, Y., Liu, X., Zheng, L., Zhang, Q., Jiao, Y., and Chen, Y. (2023). Design and discovery of new selective and potent VEGF receptor 2 tyrosine kinase inhibitors. Bioorg. Med. Chem., 91.","DOI":"10.1016\/j.bmc.2023.117404"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Eissa, I.H., El-Helby, A.-G.A., Mahdy, H.A., Khalifa, M.M., Elnagar, H.A., Mehany, A.B.M., Metwaly, A.M., Elhendawy, M.A., Radwan, M.M., and ElSohly, M.A. (2020). Discovery of new quinazolin-4(3H)-ones as VEGFR-2 inhibitors: Design, synthesis, and anti-proliferative evaluation. Bioorg. Chem., 105.","DOI":"10.1016\/j.bioorg.2020.104380"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Mahdy, H.A., Ibrahim, M.K., Metwaly, A.M., Belal, A., Mehany, A.B.M., El-Gamal, K.M.A., El-Sharkawy, A., Elhendawy, M.A., Radwan, M.M., and Elsohly, M.A. (2020). Design, synthesis, molecular modeling, in vivo studies and anticancer evaluation of quinazolin-4(3H)-one derivatives as potential VEGFR-2 inhibitors and apoptosis inducers. Bioorg. Chem., 94.","DOI":"10.1016\/j.bioorg.2019.103422"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"El-Adl, K., El-Helby, A.-G.A., Ayyad, R.R., Mahdy, H.A., Khalifa, M.M., Elnagar, H.A., Mehany, A.B.M., Metwaly, A.M., Elhendawy, M.A., and Radwan, M.M. (2021). Design, synthesis, and anti-proliferative evaluation of new quinazolin-4(3H)-ones as potential VEGFR-2 inhibitors. Bioorg. Med. Chem., 29.","DOI":"10.1016\/j.bmc.2020.115872"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Eissa, I.H., Ibrahim, M.K., Metwaly, A.M., Belal, A., Mehany, A.B.M., Abdelhady, A.A., Elhendawy, M.A., Radwan, M.M., ElSohly, M.A., and Mahdy, H.A. (2021). Design, molecular docking, in vitro, and in vivo studies of new quinazolin-4(3H)-ones as VEGFR-2 inhibitors with potential activity against hepatocellular carcinoma. Bioorg. Chem., 107.","DOI":"10.1016\/j.bioorg.2020.104532"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1016\/j.bmcl.2014.03.042","article-title":"Synthesis and biological evaluation of 2,3-diaryl isoquinolinone derivatives as anti-breast cancer agents targeting ERa and VEGFR-2","volume":"24","author":"Tang","year":"2014","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.ejmech.2016.04.029","article-title":"Design, synthesis and evaluation of 6-aryl-indenoisoquinolone derivatives dual targeting ER\u03b1 and VEGFR-2 as anti-breast cancer agents","volume":"118","author":"Tang","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1016\/j.bmcl.2016.02.037","article-title":"Synthesis and antiproliferative activity of 6,7-disubstituted-4-phenoxyquinoline derivatives bearing the 2-oxo-4-chloro-1,2-dihydroquinoline-3-carboxamide moiety","volume":"26","author":"Tang","year":"2016","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2000068","DOI":"10.1002\/ardp.202000068","article-title":"Design, synthesis, molecular docking, and anticancer evaluations of 1-benzylquinazoline-2,4(1H,3H)-dione bearing different moieties as VEGFR-2 inhibitors","volume":"353","author":"Sakr","year":"2020","journal-title":"Arch. Pharm."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"El-Fakharany, Z.S., Nissan, Y.M., Sedky, N.K., Arafa, R.K., and Abou-Seri, S.M. (2023). New proapoptotic chemotherapeutic agents based on the quinolone-3-carboxamide scaffold acting by VEGFR-2 inhibition. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-38264-w"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.ejmech.2016.02.029","article-title":"Increasing the binding affinity of VEGFR-2 inhibitors by extending their hydrophobic interaction with the active site: Design, synthesis and biological evaluation of 1-substituted-4-(4-methoxybenzyl)phthalazine derivatives","volume":"113","author":"Eldehna","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1700240","DOI":"10.1002\/ardp.201700240","article-title":"Design, Synthesis, Molecular Docking, and Anticancer Activity of Phthalazine Derivatives as VEGFR-2 Inhibitors","volume":"350","author":"Ayyad","year":"2017","journal-title":"Arch. Pharm."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Saleh, N.M., El-Gaby, M.S.A., El-Adl, K., and Abd El-Sattar, N.E.A. (2020). Design, green synthesis, molecular docking and anticancer evaluations of diazepam bearing sulfonamide moieties as VEGFR-2 inhibitors. Bioorg. Chem., 104.","DOI":"10.1016\/j.bioorg.2020.104350"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.1080\/14756366.2021.1945591","article-title":"Discovery of new 3-methylquinoxalines as potential anti-cancer agents and apoptosis inducers targeting VEGFR-2: Design, synthesis, and in silico studies","volume":"36","author":"Alanazi","year":"2021","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1080\/14756366.2021.1956488","article-title":"Design, synthesis, docking, ADMET studies, and anticancer evaluation of new 3-methylquinoxaline derivatives as VEGFR-2 inhibitors and apoptosis inducers","volume":"36","author":"Alanazi","year":"2021","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"El-Adl, K., Sakr, H.M., Yousef, R.G., Mehany, A.B.M., Metwaly, A.M., Elhendawy, M.A., Radwan, M.M., ElSohly, M.A., Abulkhair, H.S., and Eissa, I.H. (2021). Discovery of new quinoxaline-2(1H)-one-based anticancer agents targeting VEGFR-2 as inhibitors: Design, synthesis, and anti-proliferative evaluation. Bioorg. Chem., 114.","DOI":"10.1016\/j.bioorg.2021.105105"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Alanazi, M.M., Mahdy, H.A., Alsaif, N.A., Obaidullah, A.J., Alkahtani, H.M., Al-Mehizia, A.A., Alsubaie, S.M., Dahab, M.A., and Eissa, I.H. (2021). New bis([1,2,4]triazolo)[4,3-a:3\u2032,4\u2032-c]quinoxaline derivatives as VEGFR-2 inhibitors and apoptosis inducers: Design, synthesis, in silico studies, and anticancer evaluation. Bioorg. Chem., 112.","DOI":"10.1016\/j.bioorg.2021.104949"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1080\/14756366.2021.1915303","article-title":"Discovery of new VEGFR-2 inhibitors based on bis([1, 2, 4]triazolo)[4,3-a:3\u2032,4\u2032-c]quinoxaline derivatives as anticancer agents and apoptosis inducers","volume":"36","author":"Alsaif","year":"2021","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Alsaif, N.A., Dahab, M.A., Alanazi, M.M., Obaidullah, A.J., Al-Mehizia, A.A., Alanazi, M.M., Aldawas, S., Mahdy, H.A., and Elkady, H. (2021). New quinoxaline derivatives as VEGFR-2 inhibitors with anticancer and apoptotic activity: Design, molecular modeling, and synthesis. Bioorg. Chem., 110.","DOI":"10.1016\/j.bioorg.2021.104807"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Ismail, M.M.F., Shawer, T.Z., Ibrahim, R.S., Allam, R.M., and Ammar, Y.A. (2023). Novel quinoxaline-based VEGFR-2 inhibitors to halt angiogenesis. Bioorg. Chem., 139.","DOI":"10.1016\/j.bioorg.2023.106735"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Stefanachi, A., Leonetti, F., Pisani, L., Catto, M., and Carotti, A. (2018). Coumarin: A Natural, Privileged and Versatile Scaffold for Bioactive Compounds. Molecules, 23.","DOI":"10.3390\/molecules23020250"},{"key":"ref_88","first-page":"100006","article-title":"Coumarin-heterocycle framework: A privileged approach in promising anticancer drug design","volume":"2","author":"Dorababu","year":"2021","journal-title":"Eur. J. Med. Chem. Reports"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1700064","DOI":"10.1002\/ardp.201700064","article-title":"New Coumarin Derivatives as Anti-Breast and Anti-Cervical Cancer Agents Targeting VEGFR-2 and p38\u03b1 MAPK","volume":"350","author":"Batran","year":"2017","journal-title":"Arch. Pharm."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.bioorg.2018.12.040","article-title":"Synthesis, anticancer effect and molecular modeling of new thiazolylpyrazolyl coumarin derivatives targeting VEGFR-2 kinase and inducing cell cycle arrest and apoptosis","volume":"85","author":"Mohamed","year":"2019","journal-title":"Bioorg. Chem."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.ejmech.2017.09.015","article-title":"Novel SERMs based on 3-aryl-4-aryloxy-2H-chromen-2-one skeleton\u2014A possible way to dual ER\u03b1\/VEGFR-2 ligands for treatment of breast cancer","volume":"140","author":"Luo","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Ahmed, E.Y., Abdel Latif, N.A., El-Mansy, M.F., Elserwy, W.S., and Abdelhafez, O.M. (2020). VEGFR-2 inhibiting effect and molecular modeling of newly synthesized coumarin derivatives as anti-breast cancer agents. Bioorg. Med. Chem., 28.","DOI":"10.1016\/j.bmc.2020.115328"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"113102","DOI":"10.1016\/j.ejmech.2020.113102","article-title":"The application of isatin-based multicomponent-reactions in the quest for new bioactive and druglike molecules","volume":"211","author":"Marques","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1002\/tcr.202000167","article-title":"Engaging Isatins in Multicomponent Reactions (MCRs)\u2014Easy Access to Structural Diversity","volume":"21","author":"Marques","year":"2021","journal-title":"Chem. Rec."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Cheke, R.S., Patil, V.M., Firke, S.D., Ambhore, J.P., Ansari, I.A., Patel, H.M., Shinde, S.D., Pasupuleti, V.R., Hassan, M.I., and Adnan, M. (2022). Therapeutic Outcomes of Isatin and Its Derivatives against Multiple Diseases: Recent Developments in Drug Discovery. Pharmaceuticals, 15.","DOI":"10.3390\/ph15030272"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"4927","DOI":"10.1016\/j.tet.2018.06.015","article-title":"Recent advances in the asymmetric catalytic synthesis of chiral 3-hydroxy and 3-aminooxindoles and derivatives: Medicinally relevant compounds","volume":"74","author":"Burke","year":"2018","journal-title":"Tetrahedron"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.1021\/acsmedchemlett.1c00344","article-title":"Ugi Reaction Synthesis of Oxindole\u2013Lactam Hybrids as Selective Butyrylcholinesterase Inhibitors","volume":"12","author":"Leitzbach","year":"2021","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"3434","DOI":"10.1002\/ajoc.202100684","article-title":"Ugi Adducts of Isatin as Promising Antiproliferative Agents with Druglike Properties","volume":"10","author":"Puerta","year":"2021","journal-title":"Asian J. Org. Chem."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.3762\/bjoc.20.104","article-title":"The Ugi4CR as effective tool to access promising anticancer isatin-based \u03b1-acetamide carboxamide oxindole hybrids","volume":"20","author":"Marques","year":"2024","journal-title":"Beilstein J. Org. Chem."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1039\/D2NJ03627D","article-title":"Easy access to Ugi-derived isatin-peptoids and their potential as small-molecule anticancer agents","volume":"47","author":"Marques","year":"2022","journal-title":"New J. Chem."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1039\/D2MD00044J","article-title":"N-1,2,3-Triazole\u2013isatin derivatives: Anti-proliferation effects and target identification in solid tumour cell lines","volume":"13","author":"Busto","year":"2022","journal-title":"RSC Med. Chem."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.ejmech.2015.05.040","article-title":"Indoline ureas as potential anti-hepatocellular carcinoma agents targeting VEGFR-2: Synthesis, in vitro biological evaluation and molecular docking","volume":"100","author":"Eldehna","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.ejmech.2018.10.068","article-title":"Enhancement of the tail hydrophobic interactions within the carbonic anhydrase IX active site via structural extension: Design and synthesis of novel N-substituted isatins-SLC-0111 hybrids as carbonic anhydrase inhibitors and antitumor agents","volume":"162","author":"Eldehna","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.ejmech.2018.11.061","article-title":"Type IIA\u2014Type IIB protein tyrosine kinase inhibitors hybridization as an efficient approach for potent multikinase inhibitor development: Design, synthesis, anti-proliferative activity, multikinase inhibitory activity and molecular modeling of novel indolinone-based ureides and amides","volume":"163","author":"Eldehna","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"115707","DOI":"10.1016\/j.ejmech.2023.115707","article-title":"Discovery of indolinone-bearing benzenesulfonamides as new dual carbonic anhydrase and VEGFR-2 inhibitors possessing anticancer and pro-apoptotic properties","volume":"259","author":"Saied","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Alanazi, M.M., and Alanazi, A.S. (2023). Novel 7-Deazapurine Incorporating Isatin Hybrid Compounds as Protein Kinase Inhibitors: Design, Synthesis, In Silico Studies, and Antiproliferative Evaluation. Molecules, 28.","DOI":"10.3390\/molecules28155869"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"113083","DOI":"10.1016\/j.ejmech.2020.113083","article-title":"Design, synthesis, and in vitro and in vivo anti-angiogenesis study of a novel vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitor based on 1,2,3-triazole scaffold","volume":"211","author":"Wang","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"2751","DOI":"10.1021\/acs.jmedchem.9b01541","article-title":"Urea Derivatives in Modern Drug Discovery and Medicinal Chemistry","volume":"63","author":"Ghosh","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1039\/D1MD00058F","article-title":"Recent advances in urea- and thiourea-containing compounds: Focus on innovative approaches in medicinal chemistry and organic synthesis","volume":"12","author":"Ronchetti","year":"2021","journal-title":"RSC Med. Chem."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Ismail, R.S.M., El Kerdawy, A.M., Soliman, D.H., Georgey, H.H., Abdel Gawad, N.M., Angeli, A., and Supuran, C.T. (2023). Discovery of a new potent oxindole multi-kinase inhibitor among a series of designed 3-alkenyl-oxindoles with ancillary carbonic anhydrase inhibitory activity as antiproliferative agents. BMC Chem., 17.","DOI":"10.1186\/s13065-023-00994-3"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.ejmech.2014.11.032","article-title":"Discovery of novel VEGFR-2 inhibitors. Part II: Biphenyl urea incorporated with salicylaldoxime","volume":"90","author":"Gao","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"104745","DOI":"10.18632\/oncotarget.20065","article-title":"Discovery and evaluation of triple inhibitors of VEGFR-2, TIE-2 and EphB4 as anti-angiogenic and anti-cancer agents","volume":"8","author":"Zhang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"El-Naggar, M., Almahli, H., Ibrahim, H.S., Eldehna, W.M., and Abdel-Aziz, H.A. (2018). Pyridine-Ureas as Potential Anticancer Agents: Synthesis and In Vitro Biological Evaluation. Molecules, 23.","DOI":"10.3390\/molecules23061459"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/22\/5341\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:31:29Z","timestamp":1760113889000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/22\/5341"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,13]]},"references-count":113,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["molecules29225341"],"URL":"https:\/\/doi.org\/10.3390\/molecules29225341","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,13]]}}}