{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T11:57:05Z","timestamp":1773921425563,"version":"3.50.1"},"reference-count":47,"publisher":"Wiley","issue":"48","license":[{"start":{"date-parts":[[2019,12,20]],"date-time":"2019-12-20T00:00:00Z","timestamp":1576800000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007689","name":"Universidade de Aveiro","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007689","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemistrySelect"],"published-print":{"date-parts":[[2019,12,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The versatility of\n                    <jats:italic>N<\/jats:italic>\n                    \u2010methyl\u2010nitroindazolylacetonitriles as templates for further modifications was evidenced by their successfully alkylation with a series of alkyl halides using DBU as base affording the monoalkylated derivatives in high yields. Another synthetic strategy used to modify the nitroindazolylacetonitrile derivatives was the Knoevenagel condensation with a series of aldehydes in the presence of piperidine; such condensation allowed the preparation of the desired products in good to excellent yields. The reaction of a series of nitroindazolylacetonitriles with salicylaldehyde showed to be an efficient and fast methodology to prepare chromenone\u2010imine\u2010indazoles (83\u201092%), which by acid hydrolysis were converted into the corresponding chromenone\u2010indazole derivatives (88\u201094%). The structures of derivatives\n                    <jats:bold>8\u2009h<\/jats:bold>\n                    ,\n                    <jats:bold>8\u2009l<\/jats:bold>\n                    and\n                    <jats:bold>10<\/jats:bold>\n                    were unequivocally confirmed by single crystal X\u2010ray diffraction. The drug\u2010likeness properties of the compounds were evaluated\n                    <jats:italic>in silico<\/jats:italic>\n                    and none of the tested nitroindazolylacetonitriles violated the Lipinski's \u201crule of five\u201d. The antiproliferative activity against human cervical cancer cells (HeLa) and normal human dermal fibroblasts was evaluated by MTT assay and revealed that compounds\n                    <jats:bold>7\u2009b<\/jats:bold>\n                    ,\n                    <jats:bold>8\u2009d<\/jats:bold>\n                    and\n                    <jats:bold>14\u2009a<\/jats:bold>\n                    are those who presented higher antiproliferative effect against HeLa cancer cells.\n                  <\/jats:p>","DOI":"10.1002\/slct.201904344","type":"journal-article","created":{"date-parts":[[2019,12,20]],"date-time":"2019-12-20T07:33:33Z","timestamp":1576827213000},"page":"14335-14342","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Synthesis and Biological Evaluation of New Functionalized Nitroindazolylacetonitrile Derivatives"],"prefix":"10.1002","volume":"4","author":[{"given":"Mohammed","family":"Eddahmi","sequence":"first","affiliation":[{"name":"Laboratory of Organic and Analytic Chemistry, Faculty of Sciences and Technics Sultan Moulay Slimane University BP 523  2300 Beni-Mellal Morocco"},{"name":"QOPNA &amp; LAQV-REQUIMTE, Department of Chemistry University of Aveiro  3810-193 Aveiro Portugal"}]},{"given":"Nuno M. M.","family":"Moura","sequence":"additional","affiliation":[{"name":"QOPNA &amp; LAQV-REQUIMTE, Department of Chemistry University of Aveiro  3810-193 Aveiro Portugal"}]},{"given":"Latifa","family":"Bouissane","sequence":"additional","affiliation":[{"name":"Laboratory of Organic and Analytic Chemistry, Faculty of Sciences and Technics Sultan Moulay Slimane University BP 523  2300 Beni-Mellal Morocco"}]},{"given":"Maria A. F.","family":"Faustino","sequence":"additional","affiliation":[{"name":"QOPNA &amp; LAQV-REQUIMTE, Department of Chemistry University of Aveiro  3810-193 Aveiro Portugal"}]},{"given":"Jos\u00e9 A. S.","family":"Cavaleiro","sequence":"additional","affiliation":[{"name":"QOPNA &amp; LAQV-REQUIMTE, Department of Chemistry University of Aveiro  3810-193 Aveiro Portugal"}]},{"given":"Filipe A. A.","family":"Paz","sequence":"additional","affiliation":[{"name":"CICECO - Aveiro Institute of Materials, Chemistry Department University of Aveiro  3810-193 Aveiro Portugal"}]},{"given":"Ricardo F.","family":"Mendes","sequence":"additional","affiliation":[{"name":"CICECO - Aveiro Institute of Materials, Chemistry Department University of Aveiro  3810-193 Aveiro Portugal"}]},{"given":"Joana","family":"Figueiredo","sequence":"additional","affiliation":[{"name":"CICS-UBI - Centro de Investiga\u00e7\u00e3o em Ci\u00eancias da Sa\u00fade Universidade da Beira Interior  Av. Infante D. Henrique 6200-506 Covilh\u00e3 Portugal"}]},{"given":"Josu\u00e9","family":"Carvalho","sequence":"additional","affiliation":[{"name":"CICS-UBI - Centro de Investiga\u00e7\u00e3o em Ci\u00eancias da Sa\u00fade Universidade da Beira Interior  Av. Infante D. Henrique 6200-506 Covilh\u00e3 Portugal"}]},{"given":"Carla","family":"Cruz","sequence":"additional","affiliation":[{"name":"CICS-UBI - Centro de Investiga\u00e7\u00e3o em Ci\u00eancias da Sa\u00fade Universidade da Beira Interior  Av. Infante D. Henrique 6200-506 Covilh\u00e3 Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7953-8166","authenticated-orcid":false,"given":"Maria G. P. M. S.","family":"Neves","sequence":"additional","affiliation":[{"name":"QOPNA &amp; LAQV-REQUIMTE, Department of Chemistry University of Aveiro  3810-193 Aveiro Portugal"}]},{"given":"El Mostapha","family":"Rakib","sequence":"additional","affiliation":[{"name":"Laboratory of Organic and Analytic Chemistry, Faculty of Sciences and Technics Sultan Moulay Slimane University BP 523  2300 Beni-Mellal Morocco"}]}],"member":"311","published-online":{"date-parts":[[2019,12,20]]},"reference":[{"key":"e_1_2_7_1_1","unstructured":"\u00a0"},{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2018.11.059"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.2174\/1385272820666160919112919"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.11648\/j.sjc.20180605.12"},{"key":"e_1_2_7_5_1","volume-title":"The Chemistry of Heterocyclic Compounds: Pyrazoles and Reduced and Condensed Pyrazoles, Vol. 22","author":"Wiley R.","year":"2009"},{"key":"e_1_2_7_6_1","unstructured":"\u00a0"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-1280(02)00167-7"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1039\/B617988F"},{"key":"e_1_2_7_9_1","unstructured":"\u00a0"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1080\/00304948.2010.513898"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejoc.200800227"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja402761p"},{"key":"e_1_2_7_13_1","unstructured":"\u00a0"},{"key":"e_1_2_7_14_2","first-page":"1228","volume":"18","author":"Yichao W.","year":"2018","journal-title":"Anti-Cancer Agents Med. Chem."},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules23112783"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201800253"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1080\/13543776.2018.1472240"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b01208"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-894X(01)00156-1"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2007.03.024"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2009.07.067"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2011.01.027"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201600204"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2014.11.029"},{"key":"e_1_2_7_25_2","first-page":"235","volume-title":"Advances in Heterocyclic Chemistry, Vol 125, Vol. 125","author":"Hassan A. A.","year":"2018"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1039\/C8MD00475G"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2016.04.073"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2016.03.026"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2016.03.036"},{"key":"e_1_2_7_30_1","unstructured":"\u00a0"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1039\/C4TA01891E"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.inorgchem.5b01630"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1039\/C5TB01150G"},{"key":"e_1_2_7_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcis.2016.03.023"},{"key":"e_1_2_7_35_1","unstructured":"\u00a0"},{"key":"e_1_2_7_36_2","doi-asserted-by":"publisher","DOI":"10.1080\/17415993.2014.966105"},{"key":"e_1_2_7_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2005.09.037"},{"key":"e_1_2_7_38_2","doi-asserted-by":"publisher","DOI":"10.3987\/COM-11-12149"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/hc.21270"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1039\/C9NJ02807B"},{"key":"e_1_2_7_41_1","unstructured":"\u00a0"},{"key":"e_1_2_7_42_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.6b00574"},{"key":"e_1_2_7_43_2","doi-asserted-by":"publisher","DOI":"10.1039\/C0CS00027B"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b00104"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1056-8719(00)00107-6"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm020017n"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2015.03.016"}],"container-title":["ChemistrySelect"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fslct.201904344","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/slct.201904344","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/slct.201904344","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/slct.201904344","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T14:27:36Z","timestamp":1761488856000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/slct.201904344"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,20]]},"references-count":47,"journal-issue":{"issue":"48","published-print":{"date-parts":[[2019,12,30]]}},"alternative-id":["10.1002\/slct.201904344"],"URL":"https:\/\/doi.org\/10.1002\/slct.201904344","archive":["Portico"],"relation":{},"ISSN":["2365-6549","2365-6549"],"issn-type":[{"value":"2365-6549","type":"print"},{"value":"2365-6549","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,20]]},"assertion":[{"value":"2019-11-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-12-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-12-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}