{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:19:40Z","timestamp":1785435580935,"version":"3.56.0"},"reference-count":16,"publisher":"Beilstein Institut","license":[{"start":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T00:00:00Z","timestamp":1749513600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T00:00:00Z","timestamp":1749513600000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T00:00:00Z","timestamp":1749513600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1024314"],"award-info":[{"award-number":["APP1024314"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["LE0668477"],"award-info":[{"award-number":["LE0668477"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["LE140100119"],"award-info":[{"award-number":["LE140100119"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["LE0237908"],"award-info":[{"award-number":["LE0237908"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Beilstein J. Org. Chem."],"accepted":{"date-parts":[[2025,5,20]]},"abstract":"<jats:p>\n                    1,2,4-Triazolo[4,3-\n                    <jats:italic>a<\/jats:italic>\n                    ]pyrazines have previously been explored by the Open Source Malaria project as potent in vitro and in vivo antimalarial drug leads. With a view to generating a library of unique antimalarial 1,2,4-triazolo[4,3-\n                    <jats:italic>a<\/jats:italic>\n                    ]pyrazines and exploring regiochemical preference for nucleophilic amines, we utilised the known synthetic 5-chloro-3-(4-chlorophenyl)-[1,2,4]triazolo[4,3-\n                    <jats:italic>a<\/jats:italic>\n                    ]pyrazine (\n                    <jats:bold>1<\/jats:bold>\n                    ) as a scaffold for aminations with 14 commercially available primary amines. Reacting scaffold\n                    <jats:bold>1<\/jats:bold>\n                    with excess primary amine at room temperature for 16 h generated the desired amine analogues in respectable yields (18\u201387%) and high purity (\u226595%) following chromatography workup. The structures of the 14 previously undescribed amine analogues\n                    <jats:bold>2<\/jats:bold>\n                    \u2013\n                    <jats:bold>15<\/jats:bold>\n                    were fully characterised following 1D\/2D NMR, UV, and HRMS data analyses. X-ray crystallographic analysis of crystals obtained from the aminated products\n                    <jats:bold>2<\/jats:bold>\n                    ,\n                    <jats:bold>7<\/jats:bold>\n                    ,\n                    <jats:bold>10<\/jats:bold>\n                    , and\n                    <jats:bold>15<\/jats:bold>\n                    are also reported here. The new library of amine-substituted triazolopyrazines was screened against the\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    3D7 strain. The tertiary alkylamine products\n                    <jats:bold>10<\/jats:bold>\n                    \u2013\n                    <jats:bold>14<\/jats:bold>\n                    displayed antimalarial activity with IC\n                    <jats:sub>50<\/jats:sub>\n                    values ranging from 9.90 to 23.30 \u00b5M against\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    3D7, with compounds\n                    <jats:bold>10<\/jats:bold>\n                    \u2013\n                    <jats:bold>12<\/jats:bold>\n                    demonstrating no toxicity at 80 \u00b5M against the human embryonic kidney cell line HEK293.\n                  <\/jats:p>","DOI":"10.3762\/bjoc.21.90","type":"journal-article","created":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T05:02:21Z","timestamp":1749531741000},"page":"1126-1134","source":"Crossref","is-referenced-by-count":2,"title":["Investigations of amination reactions on an antimalarial 1,2,4-triazolo[4,3-\n                    <i>a<\/i>\n                    ]pyrazine scaffold"],"prefix":"10.3762","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-1026-1286","authenticated-orcid":false,"given":"Henry S T","family":"Smith","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02sc3r913","id-type":"ROR","asserted-by":"publisher"},{"id":"https:\/\/www.isni.org\/0000000404375432","id-type":"ISNI","asserted-by":"publisher"}]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Giuliani","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02sc3r913","id-type":"ROR","asserted-by":"publisher"},{"id":"https:\/\/www.isni.org\/0000000404375432","id-type":"ISNI","asserted-by":"publisher"}]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6697-5025","authenticated-orcid":false,"given":"Kanchana","family":"Wijesekera","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02sc3r913","id-type":"ROR","asserted-by":"publisher"},{"id":"https:\/\/www.isni.org\/0000000404375432","id-type":"ISNI","asserted-by":"publisher"}]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9843-7814","authenticated-orcid":false,"given":"Kah Yean","family":"Lum","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02sc3r913","id-type":"ROR","asserted-by":"publisher"},{"id":"https:\/\/www.isni.org\/0000000404375432","id-type":"ISNI","asserted-by":"publisher"}]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2814-1193","authenticated-orcid":false,"given":"Sandra","family":"Duffy","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02sc3r913","id-type":"ROR","asserted-by":"publisher"},{"id":"https:\/\/www.isni.org\/0000000404375432","id-type":"ISNI","asserted-by":"publisher"}]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2092-3413","authenticated-orcid":false,"given":"Aaron","family":"Lock","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02sc3r913","id-type":"ROR","asserted-by":"publisher"},{"id":"https:\/\/www.isni.org\/0000000404375432","id-type":"ISNI","asserted-by":"publisher"}]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0707-6257","authenticated-orcid":false,"given":"Jonathan M","family":"White","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01ej9dk98","id-type":"ROR","asserted-by":"publisher"},{"id":"https:\/\/www.isni.org\/000000012179088X","id-type":"ISNI","asserted-by":"publisher"}]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4914-2299","authenticated-orcid":false,"given":"Vicky M","family":"Avery","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02sc3r913","id-type":"ROR","asserted-by":"publisher"},{"id":"https:\/\/www.isni.org\/0000000404375432","id-type":"ISNI","asserted-by":"publisher"}]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4291-7573","authenticated-orcid":false,"given":"Rohan A","family":"Davis","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02sc3r913","id-type":"ROR","asserted-by":"publisher"},{"id":"https:\/\/www.isni.org\/0000000404375432","id-type":"ISNI","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/02sc3r913","id-type":"ROR","asserted-by":"publisher"},{"id":"https:\/\/www.isni.org\/0000000404375432","id-type":"ISNI","asserted-by":"publisher"}]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2086","published-online":{"date-parts":[[2025,6,10]]},"reference":[{"key":"ref1","volume-title":"World malaria report 2024: addressing inequity in the global malaria response","year":"2024"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-024-01008-2"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201900565"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1021\/ml2001517"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.1c00313"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c00746"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26092421"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1021\/acs.joc.0c01045"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.3762\/bjoc.19.11"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1002\/mrc.1984"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1021\/np500856u"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1016\/j.phytochem.2021.112887"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2012.11-0302"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-13-s1-p34"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.3390\/ijms242015104"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.3390\/molecules22101715"}],"container-title":["Beilstein Journal of Organic Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.beilstein-journals.org\/bjoc\/articles\/21\/90","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.beilstein-journals.org\/bjoc\/content\/pdf\/1860-5397-21-90.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.beilstein-journals.org\/bjoc\/articles\/21\/90","content-type":"text\/html","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T05:02:23Z","timestamp":1749531743000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.beilstein-journals.org\/bjoc\/articles\/21\/90"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,10]]},"references-count":16,"URL":"https:\/\/doi.org\/10.3762\/bjoc.21.90","archive":["Portico"],"relation":{},"ISSN":["1860-5397"],"issn-type":[{"value":"1860-5397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,10]]}}}