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Multi-step reactions leading to the title compounds included two amide bond formations. The first amide bond was achieved by the reaction of (\n                    <jats:italic>E<\/jats:italic>\n                    )-ethyl 4-chloro-4-oxobut-2-enoate (\n                    <jats:bold>1<\/jats:bold>\n                    ) and\n                    <jats:italic>N<\/jats:italic>\n                    <jats:sup>1<\/jats:sup>\n                    -(2,8-bis(trifluoromethyl)quinolin-4-yl) butane-1,4-diamine (\n                    <jats:bold>2<\/jats:bold>\n                    ). The obtained ester\n                    <jats:bold>3<\/jats:bold>\n                    was hydrolyzed and gave acid\n                    <jats:bold>4<\/jats:bold>\n                    , which then reacted with the selected halogenanilines in the presence of HATU\/DIEA and formed products\n                    <jats:bold>5\u201310<\/jats:bold>\n                    . Title compounds showed marked, dose dependent activity\n                    <jats:italic>in vitro<\/jats:italic>\n                    against hepatic stages of\n                    <jats:italic>Plasmodium berghei. IC<\/jats:italic>\n                    <jats:sub>50<\/jats:sub>\n                    values of the most active compounds\n                    <jats:bold>5<\/jats:bold>\n                    ,\n                    <jats:bold>7<\/jats:bold>\n                    and\n                    <jats:bold>9<\/jats:bold>\n                    bearing 3-fluoro, 3-chloro and 3-trifluoromethyl substituents were 3.04\u20134.16 \u00b5mol L\n                    <jats:sup>\u22121<\/jats:sup>\n                    , respectively. On the other hand, the compounds exerted only weak activity against the erythrocytic stages of two\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    strains (\n                    <jats:italic>Pf<\/jats:italic>\n                    3D7 and\n                    <jats:italic>Pf<\/jats:italic>\n                    Dd2)\n                    <jats:italic>in vitro<\/jats:italic>\n                    , with the exception of compound\n                    <jats:bold>5<\/jats:bold>\n                    (\n                    <jats:italic>IC<\/jats:italic>\n                    <jats:sub>50<\/jats:sub>\n                    = 2.9 \u00b5mol L\n                    <jats:sup>\u22121<\/jats:sup>\n                    ).\n                  <\/jats:p>","DOI":"10.2478\/acph-2019-0019","type":"journal-article","created":{"date-parts":[[2019,4,1]],"date-time":"2019-04-01T13:30:46Z","timestamp":1554125446000},"page":"233-248","source":"Crossref","is-referenced-by-count":7,"title":["Synthesis and antiplasmodial evaluation of novel mefloquine-based fumardiamides"],"prefix":"10.2478","volume":"69","author":[{"given":"Maja","family":"Beus","sequence":"first","affiliation":[{"name":"University of Zagreb Faculty of Pharmacy and Biochemistry Department of Medicinal Chemistry 10 000 Zagreb , Croatia"}]},{"given":"Diana","family":"Fontinha","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular Faculdade de Medicina , Universidade de Lisboa , 1649-028 Lisboa , Portugal"}]},{"given":"Jana","family":"Held","sequence":"additional","affiliation":[{"name":"University of T\u00fcbingen Institute of Tropical Medicine 72 074 T\u00fcbingen , Germany"}]},{"given":"Zrinka","family":"Raji\u0107","sequence":"additional","affiliation":[{"name":"University of Zagreb Faculty of Pharmacy and Biochemistry Department of Medicinal Chemistry 10 000 Zagreb , Croatia"}]},{"given":"Miguel","family":"Prud\u00eancio","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular Faculdade de Medicina , Universidade de Lisboa , 1649-028 Lisboa , Portugal"}]},{"given":"Branka","family":"Zorc","sequence":"additional","affiliation":[{"name":"University of Zagreb Faculty of Pharmacy and Biochemistry Department of Medicinal Chemistry 10 000 Zagreb , Croatia"}]}],"member":"374","published-online":{"date-parts":[[2019,3,28]]},"reference":[{"key":"2026051008524835379_j_acph-2019-0019_ref_001_w2aab3b7c17b1b6b1ab1ab1Aa","doi-asserted-by":"crossref","unstructured":"1. 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