{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T04:44:09Z","timestamp":1784609049278,"version":"3.55.0"},"reference-count":44,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T00:00:00Z","timestamp":1749772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Recovery and Resilience Plan (NRRP)","award":["CN00000041"],"award-info":[{"award-number":["CN00000041"]}]},{"name":"National Recovery and Resilience Plan (NRRP)","award":["CUP B93D21010860004"],"award-info":[{"award-number":["CUP B93D21010860004"]}]},{"name":"National Recovery and Resilience Plan (NRRP)","award":["Spoke 2"],"award-info":[{"award-number":["Spoke 2"]}]},{"name":"European Union\u2014Next Generation EU","award":["CN00000041"],"award-info":[{"award-number":["CN00000041"]}]},{"name":"European Union\u2014Next Generation EU","award":["CUP B93D21010860004"],"award-info":[{"award-number":["CUP B93D21010860004"]}]},{"name":"European Union\u2014Next Generation EU","award":["Spoke 2"],"award-info":[{"award-number":["Spoke 2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Over the past two decades, the copper(I)-catalyzed azide\u2013alkyne 1,3-dipolar cycloaddition (CuAAC), commonly known as click chemistry, and C\u2013H bond activation have gained significant attention and have emerged as key synthetic methodologies. In our efforts to synthesize fused nitrogen-containing heterocycles, we developed a palladium-catalyzed protocol for the synthesis of functionalized 7,10-dihydropyrrolo[3,2,1-ij][1,2,3]triazolo[4,5-c]quinolines and 5,8-dihydrobenzo[3,4][1,2,3]triazolo[4\u2032,5\u2032:5,6]azepino[1,2-a]indoles from suitable bromo-substituted N-propargyl-indoles. The reaction conditions demonstrate broad functional group compatibility including halogen, alkoxyl, cyano, ketone, and ester, affording the target compounds in good to high yields.<\/jats:p>","DOI":"10.3390\/molecules30122588","type":"journal-article","created":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T09:51:24Z","timestamp":1749808284000},"page":"2588","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Construction of 1,2,3-Triazole-Embedded Polyheterocyclic Compounds via CuAAC and C\u2013H Activation Strategies"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7792-774X","authenticated-orcid":false,"given":"Antonia","family":"Iazzetti","sequence":"first","affiliation":[{"name":"Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Universit\u00e0 Cattolica del Sacro Cuore, L.go Francesco Vito 1, 00168 Rome, Italy"},{"name":"Policlinico Universitario \u2018A. Gemelli\u2019 Foundation-IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0188-9505","authenticated-orcid":false,"given":"Dario","family":"Allevi","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Universit\u00e0 Cattolica del Sacro Cuore, L.go Francesco Vito 1, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2717-9341","authenticated-orcid":false,"given":"Giancarlo","family":"Fabrizi","sequence":"additional","affiliation":[{"name":"Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza, Universit\u00e0 di Roma, P. le A. Moro 5, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri","family":"Gazzilli","sequence":"additional","affiliation":[{"name":"Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza, Universit\u00e0 di Roma, P. le A. Moro 5, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8339-4284","authenticated-orcid":false,"given":"Antonella","family":"Goggiamani","sequence":"additional","affiliation":[{"name":"Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza, Universit\u00e0 di Roma, P. le A. Moro 5, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2350-639X","authenticated-orcid":false,"given":"Federico","family":"Marrone","sequence":"additional","affiliation":[{"name":"Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza, Universit\u00e0 di Roma, P. le A. Moro 5, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Stipa","sequence":"additional","affiliation":[{"name":"Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza, Universit\u00e0 di Roma, P. le A. Moro 5, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0360-8903","authenticated-orcid":false,"given":"Karim","family":"Ullah","sequence":"additional","affiliation":[{"name":"Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza, Universit\u00e0 di Roma, P. le A. Moro 5, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Zoppoli","sequence":"additional","affiliation":[{"name":"Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza, Universit\u00e0 di Roma, P. le A. Moro 5, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"66260","DOI":"10.1039\/C5RA12497B","article-title":"An expedient route to highly diversified [1,2,3]triazolo[1,5-a][1,4]benzodiazepines and their evaluation for antimicrobial, antiproliferative, and in silico studies","volume":"5","author":"Sudhapriya","year":"2015","journal-title":"RSC Adv."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2642","DOI":"10.1039\/C6GC00497K","article-title":"A pot-economical and diastereoselective synthesis involving catalyst-free click reaction for fused-triazolobenzodiazepines","volume":"18","author":"Zhang","year":"2016","journal-title":"Green Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3080","DOI":"10.1039\/c2ob07042a","article-title":"Fused ring aziridines as a facile entry into triazole fused tricyclic and bicyclic heterocycles","volume":"10","author":"Fang","year":"2012","journal-title":"Org. Biomol. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2815","DOI":"10.1021\/cr100120f","article-title":"Synthesis of DNA-Interactive Pyrrolo[2,1-c][1,4]benzodiazepines (PBDs)","volume":"111","author":"Antonow","year":"2011","journal-title":"Chem. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1021\/acsmedchemlett.7b00389","article-title":"Design, Synthesis, and Biological Activity of 1,2,3-Triazolobenzodiazepine BET Bromodomain Inhibitors","volume":"8","author":"Sharp","year":"2017","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"115101","DOI":"10.1016\/j.ejmech.2023.115101","article-title":"Triazole-fused pyrimidines in target-based anticancer drug discovery","volume":"249","author":"Dai","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Gour, J., Gatadi, S., Pooladanda, V., Ghouse, S.M., Malasala, S., Madhavi, Y.V., Godugu, C., and Nanduri, S. (2019). Facile synthesis of 1,2,3-triazole-fused indolo- and pyrrolo[1,4]diazepines, DNA-binding and evaluation of their anticancer activity. Bioorganic Chem., 93.","DOI":"10.1016\/j.bioorg.2019.103306"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1016\/j.drudis.2017.05.014","article-title":"The 1,2,3-triazole ring as a bioisostere in medicinal chemistry","volume":"22","author":"Bonandi","year":"2017","journal-title":"Drug Discov. Today"},{"key":"ref_9","first-page":"4889","article-title":"Progress in the Synthesis of Fused 1,2,3-Triazoles","volume":"6","author":"Kumar","year":"2021","journal-title":"Chem. Sel."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"43638","DOI":"10.1039\/C6RA06755G","article-title":"Palladium catalyzed domino reaction of 1,4-disubstituted 1,2,3-triazoles via double C\u2013H functionalization: One-pot synthesis of triazolo[1,5-f]phenanthridines","volume":"6","author":"Kumar","year":"2016","journal-title":"RSC Adv."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2710","DOI":"10.1039\/c2ra22799a","article-title":"Synthesis of fused triazolo [4, 5-d] quinoline\/chromene\/thiochromene derivatives via palladium catalysis mediated by tetrabutylammonium iodide","volume":"3","author":"Chen","year":"2013","journal-title":"RSC Adv."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1872","DOI":"10.1002\/ajoc.202000486","article-title":"Transition Metal-Catalyzed Cycloaddition of Azides with Internal Alkynes","volume":"9","author":"Ma","year":"2020","journal-title":"Asian J. Org. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"14188","DOI":"10.1039\/C6CC06194J","article-title":"Regioselective synthesis of multisubstituted 1,2,3-triazoles: Moving beyond the copper-catalyzed azide\u2013alkyne cycloaddition","volume":"52","author":"Wei","year":"2016","journal-title":"Commu. Chem. Nications"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1002\/adsc.201600918","article-title":"Recent Advances in Multicomponent Synthesis of 1,4,5-Trisubstituted 1,2,3-Triazoles","volume":"359","author":"Chen","year":"2017","journal-title":"Adv. Synth. Catal."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1002\/adsc.201400904","article-title":"Multicomponent Syntheses based upon Copper-Catalyzed Alkyne-Azide Cycloaddition","volume":"357","author":"Hassan","year":"2015","journal-title":"Adv. Synth. Catal."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1039\/b901970g","article-title":"Cu-free click cycloaddition reactions in chemical biology","volume":"39","author":"Jewett","year":"2010","journal-title":"Chem. Soc. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4905","DOI":"10.1021\/cr200409f","article-title":"Click Chemistry for Drug Development and Diverse Chemical\u2013Biology Applications","volume":"113","author":"Thirumurugan","year":"2013","journal-title":"Chem. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"108905","DOI":"10.1016\/j.dyepig.2020.108905","article-title":"Recent developments in 1,2,3-triazole-based chemosensors","volume":"185","author":"Ahmed","year":"2021","journal-title":"Dye. Pigment."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1002\/jhet.4767","article-title":"Research progress of triazole derivatives in the discovery of agricultural chemicals","volume":"61","author":"Song","year":"2024","journal-title":"J. Heterocycl. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"239","DOI":"10.2174\/092986712803414213","article-title":"Recent researches in triazole compounds as medicinal drugs","volume":"19","author":"Zhou","year":"2012","journal-title":"Curr. Med. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2307989","DOI":"10.1080\/17518253.2024.2307989","article-title":"Biological importance and synthesis of 1,2,3-triazole derivatives: A review","volume":"17","author":"Vaishnani","year":"2024","journal-title":"Green Chem. Lett. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/nchem.1607","article-title":"C\u2013H bond activation enables the rapid construction and late-stage diversification of functional molecules","volume":"5","author":"Glorius","year":"2013","journal-title":"Nat. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1021\/acscentsci.0c01413","article-title":"C\u2013H Activation: Toward Sustainability and Applications","volume":"7","author":"Dalton","year":"2021","journal-title":"ACS Cent. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1039\/C0OB00501K","article-title":"Copper catalysis in the construction of indole and benzo[b]furan rings","volume":"9","author":"Cacchi","year":"2011","journal-title":"Org. Biomol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"PR215","DOI":"10.1021\/cr100403z","article-title":"Update 1 of: Synthesis and Functionalization of Indoles Through Palladium-Catalyzed Reactions","volume":"111","author":"Cacchi","year":"2011","journal-title":"Chem. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3143","DOI":"10.1039\/D4OB02066A","article-title":"Pd-catalyzed intramolecular C\u2013H activation for the synthesis of fused-1,2,3-triazole quinolines and dihydroquinolines","volume":"23","author":"Ullah","year":"2025","journal-title":"Org. Biomol. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"9142","DOI":"10.1039\/c2ob26741a","article-title":"Dibenzo[a,c]carbazoles from 2-(2-bromoaryl)-3-arylindoles via a palladium-catalyzed intramolecular C\u2013H functionalization\/C\u2013C bond formation process","volume":"10","author":"Cacchi","year":"2012","journal-title":"Org. Biomol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1248\/cpb.57.610","article-title":"Two New Amaryllidaceae Alkaloids from the Bulbs of Lycoris radiata","volume":"57","author":"Wang","year":"2009","journal-title":"Chem. Pharm. Bull."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1021\/jm00361a010","article-title":"Synthesis and anticonvulsant activity of some tetracyclic indole derivatives","volume":"26","author":"Stanton","year":"1983","journal-title":"J. Med. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/S0960-894X(00)00141-4","article-title":"Pyrrolo[3,2,1-ij]quinoline derivatives, a 5-HT2c receptor agonist with selectivity over the 5-HT2a receptor: Potential therapeutic applications for epilepsy and obesity","volume":"10","author":"Isaac","year":"2000","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.bmcl.2008.12.039","article-title":"Discovery of pentacyclic compounds as potent inhibitors of hepatitis C virus NS5B RNA polymerase","volume":"19","author":"Habermann","year":"2009","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1021\/jm980684+","article-title":"Mapping the Melatonin Receptor. 6. Melatonin Agonists and Antagonists Derived from 6H-Isoindolo[2,1-a]indoles, 5,6-Dihydroindolo[2,1-a]isoquinolines, and 6,7-Dihydro-5H-benzo[c]azepino[2,1-a]indoles","volume":"43","author":"Faust","year":"2000","journal-title":"J. Med. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2696","DOI":"10.1016\/j.bmcl.2008.03.015","article-title":"Identification of prostaglandin D2 receptor antagonists based on a tetrahydropyridoindole scaffold","volume":"18","author":"Beaulieu","year":"2008","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1002\/adfm.200600055","article-title":"A DCM-Type Red-Fluorescent Dopant for High-Performance Organic Electroluminescent Devices","volume":"17","author":"Yao","year":"2007","journal-title":"Adv. Funct. Mater."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"8078","DOI":"10.1002\/anie.200902440","article-title":"Copper-Catalyzed C-C Bond Formation through C\u2013H Functionalization: Synthesis of Multisubstituted Indoles from N-Aryl Enaminones","volume":"48","author":"Bernini","year":"2009","journal-title":"Angewandte Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6738","DOI":"10.1016\/j.tetlet.2007.07.077","article-title":"Pd-catalyzed reduction of aryl halides using dimethylformamide as the hydride source","volume":"48","author":"Zawisza","year":"2007","journal-title":"Tetrahedron Lett."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"8313","DOI":"10.1016\/j.tet.2009.06.091","article-title":"N,N-Dimethylformamide: Much more than a solvent","volume":"65","author":"Muzart","year":"2009","journal-title":"Tetrahedron"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5428","DOI":"10.1021\/om400713y","article-title":"Solvent-Induced Reduction of Palladium-Aryls, a Potential Interference in Pd Catalysis","volume":"32","author":"Espinet","year":"2013","journal-title":"Organometallics"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"9346","DOI":"10.1016\/j.tet.2015.10.002","article-title":"A facile palladium-catalyzed route to 2,5,7-trisubstituted indoles","volume":"71","author":"Cacchi","year":"2015","journal-title":"Tetrahedron"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3457","DOI":"10.1021\/ol8012292","article-title":"2-Arylhydroxytyrosol Derivatives via Suzuki\u2212Miyaura Cross-Coupling","volume":"10","author":"Bernini","year":"2008","journal-title":"Org. Lett."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1246\/cl.2010.1118","article-title":"Overview of the Mechanistic Work on the Concerted Metallation\u2013Deprotonation Pathway","volume":"39","author":"Lapointe","year":"2010","journal-title":"Chem. Lett."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2333","DOI":"10.1021\/ol070697u","article-title":"Direct Pd-Catalyzed Arylation of1,2,3-Triazoles","volume":"9","author":"Chuprakov","year":"2007","journal-title":"Org. Lett."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1039\/C0CC02472D","article-title":"Synthesis of phosphonamidate peptides by Staudinger reactions of silylated phosphinic acids and esters","volume":"47","author":"Wilkening","year":"2011","journal-title":"Chem. Commun."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"15028","DOI":"10.1021\/acs.jmedchem.2c00432","article-title":"A 1, 2, 3-Triazole derivative of quinazoline exhibits antitumor activity by tethering RNF168 to SQSTM1\/P62","volume":"65","author":"Wang","year":"2022","journal-title":"J. Med. Chem."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/12\/2588\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:51:34Z","timestamp":1760032294000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/12\/2588"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,13]]},"references-count":44,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["molecules30122588"],"URL":"https:\/\/doi.org\/10.3390\/molecules30122588","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,13]]}}}