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The synthesis followed established routes starting with esters <jats:bold>9<\/jats:bold> or <jats:bold>15<\/jats:bold> and anhydride <jats:bold>21<\/jats:bold>. The synthesized 3\u2010arylpyrazoles and 3\u2010aryl\u20101,2,4\u2010triazoles had only very low antileishmanial activity. The 2\u2010fluorophenyl\u2010substituted pyrazole <jats:bold>18c<\/jats:bold> revealed the highest antileishmanial activity of this series of compounds, but its <jats:italic>IC<\/jats:italic><jats:sub>50<\/jats:sub> value (20\u2005\u03bcM) still indicates low activity. However, low micromolar antitrypanosomal activity was detected for the pyridin\u20103\u2010yl\u2010substituted pyrazoles <jats:bold>12b<\/jats:bold> (<jats:italic>IC<\/jats:italic><jats:sub>50<\/jats:sub>=4.7\u2005\u03bcM) and <jats:bold>14a<\/jats:bold> (<jats:italic>IC<\/jats:italic><jats:sub>50<\/jats:sub>=2.1\u2005\u03bcM). Their <jats:italic>IC<\/jats:italic><jats:sub>50<\/jats:sub> values are comparable with the <jats:italic>IC<\/jats:italic><jats:sub>50<\/jats:sub> values of the reference compounds benznidazole and nifurtimox. Whereas only low unspecific cytotoxicity at the primary peritoneal mouse macrophages (PMM) was detected, considerable cytotoxicity at MRC\u20105 human fibroblast cells was found for both pyrazoles <jats:bold>12b<\/jats:bold> an <jats:bold>14a<\/jats:bold>. The activity of pyrazole <jats:bold>12b<\/jats:bold> against <jats:italic>T. cruzi<\/jats:italic> is 4\u2010fold higher than its unspecific MRC\u20105 cytotoxicity.<\/jats:p>","DOI":"10.1002\/cmdc.202400220","type":"journal-article","created":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T16:08:46Z","timestamp":1714493326000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["N\u2010Pyrazolyl\u2010 and N\u2010Triazolylamines and \u2010Ureas as Antileishmanial and Antitrypanosomal Drugs"],"prefix":"10.1002","volume":"19","author":[{"given":"Tobias","family":"Winge","sequence":"first","affiliation":[{"name":"Universit\u00e4t M\u00fcnster Institut f\u00fcr Pharmazeutische und Medizinische Chemie  Corrensstra\u00dfe 48 D-48149 M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Imberg","sequence":"additional","affiliation":[{"name":"Universit\u00e4t M\u00fcnster Institut f\u00fcr Pharmazeutische und Medizinische Chemie  Corrensstra\u00dfe 48 D-48149 M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Perry","sequence":"additional","affiliation":[{"name":"Drugs for Neglected Diseases initiative  15 chemin Camille-Vidart 1202 Geneva Switzerland"},{"name":"current Address: Medicxi Ventures  10 Cours de Rive 1204 Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An","family":"Matheeussen","sequence":"additional","affiliation":[{"name":"University of Antwerpen Laboratory of Microbiology, Parasitology and Hygiene (LMPH), Infla-Med Centre of Excellence, Campus CDE, S7.24  Universiteitsplein 1 B-2610 Wilrijk-Antwerpen"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Caljon","sequence":"additional","affiliation":[{"name":"University of Antwerpen Laboratory of Microbiology, Parasitology and Hygiene (LMPH), Infla-Med Centre of Excellence, Campus CDE, S7.24  Universiteitsplein 1 B-2610 Wilrijk-Antwerpen"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitrii","family":"Kalinin","sequence":"additional","affiliation":[{"name":"Universit\u00e4t M\u00fcnster Institut f\u00fcr Pharmazeutische und Medizinische Chemie  Corrensstra\u00dfe 48 D-48149 M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9030-8417","authenticated-orcid":false,"given":"Bernhard","family":"W\u00fcnsch","sequence":"additional","affiliation":[{"name":"Universit\u00e4t M\u00fcnster Institut f\u00fcr Pharmazeutische und Medizinische Chemie  Corrensstra\u00dfe 48 D-48149 M\u00fcnster Germany"},{"name":"GRK 2515 Chemical biology of ion channels (Chembion) Universit\u00e4t M\u00fcnster  Corrensstr. 48 D-48149 M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,6,19]]},"reference":[{"key":"e_1_2_9_1_1","unstructured":"WHO \u201cIntegrating Neglected Tropical Diseases into Global Health and Development\u201d to be found under https:\/\/apps.who.int\/iris\/bitstream\/handle\/10665\/255011\/9789241565448-eng.pdf?sequence=1 2017."},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-13822-1"},{"key":"e_1_2_9_3_1","unstructured":"World Health Organization World Health Organ. 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