{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:48:39Z","timestamp":1792003719006,"version":"4.4.0"},"reference-count":49,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2026,10,14]]},"abstract":"<jats:p>\n                    In this work, a versatile and efficient synthetic strategy for the selective\n                    <jats:italic>N<\/jats:italic>\n                    \u20101 alkylation of nitro\u2010substituted 3\u2010haloindazoles was developed using a complex base of NaH\/\n                    <jats:italic>t<\/jats:italic>\n                    \u2010BuOK. Various alkylating agents were employed under an argon atmosphere in DMF. This method successfully yielded several\n                    <jats:italic>N<\/jats:italic>\n                    \u20101\u2010alkylated indazole derivatives, including 1\u2010benzyl\u20103\u2010chloro\u20106\u2010nitro\u20101\n                    <jats:italic>H<\/jats:italic>\n                    \u2010indazole, 1\u2010benzyl\u20103\u2010bromo\u20106\u2010nitro\u20101\n                    <jats:italic>H<\/jats:italic>\n                    \u2010indazole, and related analogs, with good to excellent yields (62%\u2013100%). Subsequent amination reactions of the 3\u2010bromoindazole intermediates with anilines provided\n                    <jats:italic>N<\/jats:italic>\n                    \u2010arylindazoles at the C\u20103 position in moderate yields (11%\u201370%). In parallel, Suzuki\u2013Miyaura cross\u2010coupling reactions with boronic acids provided direct access to arylindazoles at the C\u20103 position with yields ranging from 54% to 92%. Of the compounds evaluated biologically,\n                    <jats:bold>16<\/jats:bold>\n                    and\n                    <jats:bold>18c<\/jats:bold>\n                    stand out, having shown high inhibition of CDK2 (100% at 10\u2009\u03bcM), while\n                    <jats:bold>13e<\/jats:bold>\n                    and\n                    <jats:bold>16<\/jats:bold>\n                    showed maximum inhibition of ERK2 (100% at 10\u2009\u03bcM), both proteins implicated in cancer.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.70522","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T06:25:43Z","timestamp":1791527143000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synthesis of Substituted Indazoles With Potential Kinase Inhibitory Activity"],"prefix":"10.1002","volume":"21","author":[{"given":"Achraf","family":"Hibot","sequence":"first","affiliation":[{"name":"Laboratory of Medicinal Chemistry Department of Pharmacology, Toxicology and Medicinal Chemistry Faculty of Pharmacy and Food Sciences University of Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abderrafia","family":"Hafid","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Chemistry, Materials and Catalysis Faculty of Sciences and Technics Sultan Moulay Slimane University  Beni\u2010Mellal Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5858-5334","authenticated-orcid":false,"given":"Mostafa","family":"Khouili","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Chemistry, Materials and Catalysis Faculty of Sciences and Technics Sultan Moulay Slimane University  Beni\u2010Mellal Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1061-034X","authenticated-orcid":false,"given":"Maria Dolors","family":"Pujol","sequence":"additional","affiliation":[{"name":"Laboratory of Medicinal Chemistry Department of Pharmacology, Toxicology and Medicinal Chemistry Faculty of Pharmacy and Food Sciences University of Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,8]]},"reference":[{"key":"e_1_2_9_2_1","volume-title":"Heterocyclic Chemistry","author":"Gilchrist T. L.","year":"1997"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871520620666200705214917"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2021.113165"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871523017666180126150901"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.4155\/fmc\u20102019\u20100063"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612826666200417154810"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570163814666170915134018"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2020.115585"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2020.1713771"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/11110867"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tetlet.2007.07.162"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo0613784"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tetlet.2005.03.157"},{"key":"e_1_2_9_15_1","first-page":"191","article-title":"Silica Sulfuric Acid: An Efficient Catalyst for the Synthesis of Substituted Indazoles","volume":"3","author":"Gaikwad D. D.","year":"2010","journal-title":"Journal of the Iranian Chemical Research"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2007.01.010"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1039\/D3OB00121K"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S109640"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265\u2010015\u20100483\u2010x"},{"key":"e_1_2_9_20_1","first-page":"33","volume-title":"Small Molecules in Oncology. Recent Results in Cancer Research","author":"Kelly R. J.","year":"2010"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.13753"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1080\/1120009X.1992.11739190"},{"key":"e_1_2_9_23_1","first-page":"127","article-title":"Benzydamine Hydrochloride (Tantum) in the Management of Oral Inflammatory Conditions","volume":"61","author":"Turnbull R. S.","year":"1995","journal-title":"Journal of the Canadian Dental Association"},{"key":"e_1_2_9_24_1","first-page":"1169","article-title":"The Efficacy and Safety of Indisetron Hydrochloride for the Management of Nausea\/Vomiting Caused by Chemotherapy for Gynecologic Cancer","volume":"35","author":"Ushijima K.","year":"2008","journal-title":"Cancer and Chemotherapy"},{"key":"e_1_2_9_25_1","first-page":"1489","article-title":"The Efficacy of Indisetron Hydrochloride for the Management of Chemotherapy\u2010Induced Nausea and Vomiting for Lung Cancer","volume":"36","author":"Iritani E.","year":"2009","journal-title":"Cancer and Chemotherapy"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11523\u2010018\u20100582\u20101"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1RA03979B"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201800253"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2025.109083"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2008.11.105"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2016.04.029"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/ddr.21979"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm0490890"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2023.133523"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4RA00598H"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.3762\/bjoc.17.127"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.joc.1c00560"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/jhet.5570200538"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2006.07.011"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.6b00512"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1021\/ar800098p"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/jhet.1602"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.oprd.2c00051"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201600182"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1080\/00397911003707212"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tetlet.2015.11.071"},{"key":"e_1_2_9_47_1","first-page":"2799","article-title":"Halogenation of Indazole and Its Derivatives With Complex Compounds of Halogens and Dioxane","volume":"34","author":"Pozharskii F. T.","year":"1964","journal-title":"Journal of General Chemistry of the USSR"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2018.11.037"},{"key":"e_1_2_9_49_1","unstructured":"Eurofinsdiscovery accessed September\u00a010 2025 https:\/\/emea.eurofinsdiscovery.com\/catalog\/cdk2\u2010cyclina\u2010human\u2010cmgc\u2010kinase\u2010enzymatic\u2010radiometric\u2010km\u2010atp\u2010kinaseprofiler\u2010leadhunter\u2010assay\u2010fr\/14\u2010448KP."},{"key":"e_1_2_9_50_1","unstructured":"Eurofinsdiscovery accessed September 10 2025 https:\/\/emea.eurofinsdiscovery.com\/catalog\/erk2\u2010mapk1\u2010human\u2010cmgc\u2010kinase\u2010kinomescan\u2010kdelect\u2010binding\u2010leadhunter\u2010assay\u2010us\/87\u20100007\u20101150."}],"container-title":["ChemMedChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.70522","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cmdc.70522","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.70522","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:08:22Z","timestamp":1792001302000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cmdc.70522"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,8]]},"references-count":49,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2026,10,14]]}},"alternative-id":["10.1002\/cmdc.70522"],"URL":"https:\/\/doi.org\/10.1002\/cmdc.70522","archive":["Portico"],"relation":{},"ISSN":["1860-7179","1860-7187"],"issn-type":[{"value":"1860-7179","type":"print"},{"value":"1860-7187","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,8]]},"assertion":[{"value":"2025-12-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70522"}}