{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T14:06:20Z","timestamp":1770473180078,"version":"3.49.0"},"reference-count":37,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bioorganic Chemistry"],"published-print":{"date-parts":[[2021,12]]},"DOI":"10.1016\/j.bioorg.2021.105359","type":"journal-article","created":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T11:40:20Z","timestamp":1632224420000},"page":"105359","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":18,"special_numbering":"C","title":["Property activity refinement of 2-anilino 4-amino substituted quinazolines as antimalarials with fast acting asexual parasite activity"],"prefix":"10.1016","volume":"117","author":[{"given":"Trent D.","family":"Ashton","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Ngo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Favuzza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hayley E.","family":"Bullen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria R.","family":"Gancheva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ornella","family":"Romeo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Molly","family":"Parkyn Schneider","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nghi","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan W.J.","family":"Steel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Duffy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kym N.","family":"Lowes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helene Jousset","family":"Sabroux","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vicky M.","family":"Avery","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin A.","family":"Boddey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danny W.","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan F.","family":"Cowman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul R.","family":"Gilson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brad E.","family":"Sleebs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.bioorg.2021.105359_b0005","author":"World Malaria Report"},{"issue":"1\u20132 Suppl","key":"10.1016\/j.bioorg.2021.105359_b0010","doi-asserted-by":"crossref","first-page":"97","DOI":"10.4269\/ajtmh.2001.64.97","article-title":"The neglected burden of Plasmodium vivax malaria","volume":"64","author":"Mendis","year":"2001","journal-title":"Am. J. Trop. Med. Hyg."},{"issue":"10","key":"10.1016\/j.bioorg.2021.105359_b0015","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1016\/j.pt.2016.07.001","article-title":"Persistent parasitism: the adaptive biology of malariae and ovale Malaria","volume":"32","author":"Sutherland","year":"2016","journal-title":"Trends Parasitol."},{"issue":"7","key":"10.1016\/j.bioorg.2021.105359_b0020","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/j.cmi.2015.03.017","article-title":"Human infections with Plasmodium knowlesi\u2013zoonotic malaria","volume":"21","author":"Millar","year":"2015","journal-title":"Clin. Microbiol Infect."},{"issue":"5","key":"10.1016\/j.bioorg.2021.105359_b0025","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1056\/NEJMoa1314981","article-title":"Spread of Artemisinin resistance in Plasmodium falciparum Malaria","volume":"371","author":"Ashley","year":"2014","journal-title":"N. Engl. J. Med."},{"issue":"10","key":"10.1016\/j.bioorg.2021.105359_b0030","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1038\/s41591-020-1005-2","article-title":"Emergence and clonal expansion of in vitro artemisinin-resistant Plasmodium falciparum kelch13 R561H mutant parasites in Rwanda","volume":"26","author":"Uwimana","year":"2020","journal-title":"Nat. Med."},{"issue":"23","key":"10.1016\/j.bioorg.2021.105359_b0035","doi-asserted-by":"crossref","first-page":"10526","DOI":"10.1021\/acs.jmedchem.9b00761","article-title":"The development process for discovery and clinical advancement of modern antimalarials","volume":"62","author":"Ashton","year":"2019","journal-title":"J. Med. Chem."},{"issue":"3","key":"10.1016\/j.bioorg.2021.105359_b0040","doi-asserted-by":"crossref","first-page":"e01804","DOI":"10.1128\/AAC.01804-18","article-title":"Evaluation of 4-amino 2-anilinoquinazolines against Plasmodium and other apicomplexan parasites in vitro and in a P. falciparum humanized NOD-scid IL2R\u03b3(null) mouse model of malaria","volume":"63","author":"Gilson","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"issue":"3","key":"10.1016\/j.bioorg.2021.105359_b0045","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1021\/acs.jmedchem.6b01673","article-title":"Optimization of 2-anilino 4-amino substituted qinazolines into potent antimalarial agents with oral in vivo activity","volume":"60","author":"Gilson","year":"2017","journal-title":"J. Med. Chem."},{"issue":"3","key":"10.1016\/j.bioorg.2021.105359_b0050","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1021\/jm401760c","article-title":"2,4-Diaminothienopyrimidines as orally active antimalarial agents","volume":"57","author":"Gonz\u00e1lez Cabrera","year":"2014","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2021.105359_b0055","doi-asserted-by":"crossref","first-page":"6715","DOI":"10.1038\/ncomms7715","article-title":"Triaminopyrimidine is a fast-killing and long-acting antimalarial clinical candidate","volume":"6","author":"Hameed","year":"2015","journal-title":"Nat. Commun."},{"issue":"2","key":"10.1016\/j.bioorg.2021.105359_b0060","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1128\/AAC.04419-14","article-title":"Histone methyltransferase inhibitors are orally bioavailable, fast-acting molecules with activity against different species causing malaria in humans","volume":"59","author":"Malmquist","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"issue":"14","key":"10.1016\/j.bioorg.2021.105359_b0065","doi-asserted-by":"crossref","first-page":"4027","DOI":"10.1016\/j.bmcl.2010.05.095","article-title":"Discovery of novel 1H-imidazol-2-yl-pyrimidine-4,6-diamines as potential antimalarials","volume":"20","author":"Deng","year":"2010","journal-title":"Bioorg. Med. Chem. Lett."},{"issue":"1","key":"10.1016\/j.bioorg.2021.105359_b0070","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.bmcl.2009.10.133","article-title":"Synthesis and antiplasmodial activity of novel 2,4-diaminopyrimidines","volume":"20","author":"Martyn","year":"2010","journal-title":"Bioorg. Med. Chem. Lett."},{"issue":"17","key":"10.1016\/j.bioorg.2021.105359_b0075","doi-asserted-by":"crossref","first-page":"6985","DOI":"10.1021\/jm4008642","article-title":"Evaluating the differences in cycloalkyl ether metabolism using the design parameter \u201clipophilic metabolism efficiency\u201d (LipMetE) and a matched molecular pairs analysis","volume":"56","author":"Stepan","year":"2013","journal-title":"J. Med. Chem."},{"issue":"1","key":"10.1016\/j.bioorg.2021.105359_b0080","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s12936-016-1675-x","article-title":"New developments in anti-malarial target candidate and product profiles","volume":"16","author":"Burrows","year":"2017","journal-title":"Malar. J."},{"issue":"3","key":"10.1016\/j.bioorg.2021.105359_b0085","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1073\/pnas.91.3.1143","article-title":"Selection for mefloquine resistance in Plasmodium falciparum is linked to amplification of the pfmdr1 gene and cross-resistance to halofantrine and quinine","volume":"91","author":"Cowman","year":"1994","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"6272","key":"10.1016\/j.bioorg.2021.105359_b0090","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/345255a0","article-title":"Several alleles of the multidrug-resistance gene are closely linked to chloroquine resistance in Plasmodium falciparum","volume":"345","author":"Foote","year":"1990","journal-title":"Nature"},{"issue":"6220","key":"10.1016\/j.bioorg.2021.105359_b0095","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1126\/science.1260867","article-title":"Drug resistance. K13-propeller mutations confer artemisinin resistance in Plasmodium falciparum clinical isolates","volume":"347","author":"Straimer","year":"2015","journal-title":"Science"},{"key":"10.1016\/j.bioorg.2021.105359_b0100","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1186\/1475-2875-12-408","article-title":"Identification of inhibitors of Plasmodium falciparum gametocyte development","volume":"12","author":"Duffy","year":"2013","journal-title":"Malaria J."},{"issue":"9","key":"10.1016\/j.bioorg.2021.105359_b0105","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1080\/15548627.2015.1067361","article-title":"Long-term live imaging reveals cytosolic immune responses of host hepatocytes against Plasmodium infection and parasite escape mechanisms","volume":"11","author":"Prado","year":"2015","journal-title":"Autophagy"},{"issue":"1","key":"10.1016\/j.bioorg.2021.105359_b0110","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.molbiopara.2004.04.007","article-title":"A Plasmodium berghei reference line that constitutively expresses GFP at a high level throughout the complete life cycle","volume":"137","author":"Franke-Fayard","year":"2004","journal-title":"Mol. Biochem. Parasitol."},{"key":"10.1016\/j.bioorg.2021.105359_b0115","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.ejmech.2018.05.022","article-title":"Enhanced antimalarial activity of plasmepsin V inhibitors by modification of the P(2) position of PEXEL peptidomimetics","volume":"154","author":"Nguyen","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.bioorg.2021.105359_b0120","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1038\/ncomms2612","article-title":"Expansion of host cellular niche can drive adaptation of a zoonotic malaria parasite to humans","volume":"4","author":"Lim","year":"2013","journal-title":"Nat. Commun."},{"issue":"3","key":"10.1016\/j.bioorg.2021.105359_b0125","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1128\/AAC.01881-12","article-title":"Defining the timing of action of antimalarial drugs against Plasmodium falciparum","volume":"57","author":"Wilson","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.bioorg.2021.105359_b0130","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2021.113253","article-title":"Structure activity refinement of phenylsulfonyl piperazines as antimalarials that block erythrocytic invasion","volume":"214","author":"Nguyen","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.bioorg.2021.105359_b0135","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1186\/s12936-015-1011-x","article-title":"An improved SYBR Green-1-based fluorescence method for the routine monitoring of Plasmodium falciparum resistance to anti-malarial drugs","volume":"14","author":"Dery","year":"2015","journal-title":"Malar. J."},{"issue":"11","key":"10.1016\/j.bioorg.2021.105359_b0140","doi-asserted-by":"crossref","first-page":"e112571","DOI":"10.1371\/journal.pone.0112571","article-title":"Plasmodium falciparum transfected with ultra bright NanoLuc luciferase offers high sensitivity detection for the screening of growth and cellular trafficking inhibitors","volume":"9","author":"Azevedo","year":"2014","journal-title":"PloS one"},{"key":"10.1016\/j.bioorg.2021.105359_b0145","doi-asserted-by":"crossref","first-page":"37502","DOI":"10.1038\/srep37502","article-title":"Identification of inhibitors that dually target the new permeability pathway and dihydroorotate dehydrogenase in the blood stage of Plasmodium falciparum","volume":"6","author":"Dickerman","year":"2016","journal-title":"Sci. Rep."},{"issue":"6","key":"10.1016\/j.bioorg.2021.105359_b0150","doi-asserted-by":"crossref","first-page":"739","DOI":"10.4269\/ajtmh.1993.48.739","article-title":"Parasite lactate dehydrogenase as an assay for Plasmodium falciparum drug sensitivity","volume":"48","author":"Makler","year":"1993","journal-title":"Am. J. Trop. Med. Hyg."},{"issue":"1","key":"10.1016\/j.bioorg.2021.105359_b0155","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1186\/1475-2875-12-408","article-title":"Identification of inhibitors of Plasmodium falciparum gametocyte development","volume":"12","author":"Duffy","year":"2013","journal-title":"Malar. J."},{"issue":"5","key":"10.1016\/j.bioorg.2021.105359_b0160","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1038\/nprot.2016.056","article-title":"Large-scale production of Plasmodium falciparum gametocytes for malaria drug discovery","volume":"11","author":"Duffy","year":"2016","journal-title":"Nat. Protoc."},{"issue":"4","key":"10.1016\/j.bioorg.2021.105359_b0165","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/j.chom.2020.02.005","article-title":"Dual plasmepsin-targeting antimalarial agents disrupt multiple stages of the malaria parasite life cycle","volume":"27","author":"Favuzza","year":"2020","journal-title":"Cell Host Microbe"},{"issue":"11","key":"10.1016\/j.bioorg.2021.105359_b0170","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1016\/S0090-9556(24)14938-0","article-title":"Prediction of human clearance of twenty-nine drugs from hepatic microsomal intrinsic clearance data: an examination of in vitro half-life approach and non-specific binding to microsomes","volume":"27","author":"Obach","year":"1999","journal-title":"Drug Metab. Dispos."},{"issue":"10","key":"10.1016\/j.bioorg.2021.105359_b0175","doi-asserted-by":"crossref","first-page":"5148","DOI":"10.1021\/acs.jmedchem.9b00462","article-title":"Identification of 5-substituted 2-acylaminothiazoles that activate tat-mediated transcription in HIV-1 latency models","volume":"62","author":"Nguyen","year":"2019","journal-title":"J. Med. Chem."},{"issue":"8","key":"10.1016\/j.bioorg.2021.105359_b0180","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1021\/ac9912247","article-title":"A high-throughput screening method for the determination of aqueous drug solubility using laser nephelometry in microtiter plates","volume":"72","author":"Bevan","year":"2000","journal-title":"Anal. Chem."},{"key":"10.1016\/j.bioorg.2021.105359_b0185","unstructured":"Calculator Plugins were used for structure property prediction and calculation, MarvinSketch 6.0.6., 2013, ChemAxon (http:\/\/www.chemaxon.com)."}],"container-title":["Bioorganic Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0045206821007367?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0045206821007367?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T08:23:31Z","timestamp":1758615811000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0045206821007367"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12]]},"references-count":37,"alternative-id":["S0045206821007367"],"URL":"https:\/\/doi.org\/10.1016\/j.bioorg.2021.105359","relation":{},"ISSN":["0045-2068"],"issn-type":[{"value":"0045-2068","type":"print"}],"subject":[],"published":{"date-parts":[[2021,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Property activity refinement of 2-anilino 4-amino substituted quinazolines as antimalarials with fast acting asexual parasite activity","name":"articletitle","label":"Article Title"},{"value":"Bioorganic Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bioorg.2021.105359","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"105359"}}