{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T12:21:25Z","timestamp":1789474885940,"version":"build-2803163510"},"reference-count":51,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2021,8,4]],"date-time":"2021-08-04T00:00:00Z","timestamp":1628035200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2021,12,14]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Herein we report a microscale parallel synthetic approach allowing for rapid access to libraries of N\u2010acylated aminotriazoles and screening of their inhibitory activity against factor XIIa (FXIIa) and thrombin, which are targets for antithrombotic drugs. This approach, in combination with post\u2010screening structure optimization, yielded a potent 7\u2005nM inhibitor of FXIIa and a 25\u2005nM thrombin inhibitor; both compounds showed no inhibition of the other tested serine proteases. Selected N\u2010acylated aminotriazoles exhibited anticoagulant properties <jats:italic>in<\/jats:italic>\u2005<jats:italic>vitro<\/jats:italic> influencing the intrinsic blood coagulation pathway, but not extrinsic coagulation. Mechanistic studies of FXIIa inhibition suggested that synthesized N\u2010acylated aminotriazoles are covalent inhibitors of FXIIa. These synthesized compounds may serve as a promising starting point for the development of novel antithrombotic drugs.<\/jats:p>","DOI":"10.1002\/cmdc.202100431","type":"journal-article","created":{"date-parts":[[2021,7,18]],"date-time":"2021-07-18T22:11:42Z","timestamp":1626646302000},"page":"3672-3690","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Microscale Parallel Synthesis of Acylated Aminotriazoles Enabling the Development of Factor XIIa and Thrombin Inhibitors"],"prefix":"10.1002","volume":"16","author":[{"given":"Simon","family":"Platte","sequence":"first","affiliation":[{"name":"Institute of Pharmaceutical and Medicinal Chemistry University of M\u00fcnster  Corrensstr. 48 48149 M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marvin","family":"Korff","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical and Medicinal Chemistry University of M\u00fcnster  Corrensstr. 48 48149 M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Imberg","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical and Medicinal Chemistry University of M\u00fcnster  Corrensstr. 48 48149 M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilker","family":"Balicioglu","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical and Medicinal Chemistry University of M\u00fcnster  Corrensstr. 48 48149 M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catharina","family":"Erbacher","sequence":"additional","affiliation":[{"name":"Institute of Inorganic and Analytical Chemistry University of M\u00fcnster  Corrensstr. 30 48149 M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas M.","family":"Will","sequence":"additional","affiliation":[{"name":"Institute of Inorganic and Analytical Chemistry University of M\u00fcnster  Corrensstr. 30 48149 M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6709-3673","authenticated-orcid":false,"given":"Constantin G.","family":"Daniliuc","sequence":"additional","affiliation":[{"name":"Institute for Organic Chemistry University of M\u00fcnster  Corrensstr. 40 48149 M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1774-6787","authenticated-orcid":false,"given":"Uwe","family":"Karst","sequence":"additional","affiliation":[{"name":"Institute of Inorganic and Analytical Chemistry University of M\u00fcnster  Corrensstr. 30 48149 M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2717-5364","authenticated-orcid":false,"given":"Dmitrii V.","family":"Kalinin","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical and Medicinal Chemistry University of M\u00fcnster  Corrensstr. 48 48149 M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,8,4]]},"reference":[{"key":"e_1_2_7_1_1","unstructured":"D. Ashorobi M.\u2005A. Ameer R. Fernandez inStatPearls Treasure Island (FL) 2021."},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH16-10-0807"},{"key":"e_1_2_7_3_1","unstructured":"\u00a0"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1160\/TH07-03-0183"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1527-3466.1991.tb00415.x"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0201377"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2016.01.023"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2018016337"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c01635"},{"key":"e_1_2_7_10_1","unstructured":"\u00a0"},{"key":"e_1_2_7_11_2","first-page":"120","volume":"9","author":"Previtali E.","year":"2011","journal-title":"Blood Transfus"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11239-013-0899-7"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.12.018"},{"key":"e_1_2_7_14_1","unstructured":"\u00a0"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0030-1268866"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hest.2020.01.001"},{"key":"e_1_2_7_17_1","unstructured":"\u00a0"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2020.112753"},{"key":"e_1_2_7_19_2","author":"Kalinin D. V.","year":"2021","journal-title":"Expert Opin. Ther. Pat."},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02011"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(96)79479-1"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.3235"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2020.04.020"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0039-1692439"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2017.08.056"},{"key":"e_1_2_7_26_1","unstructured":"\u00a0"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1039\/C1CC15210F"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201104055"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1080\/00397910701860372"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr100048w"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2005.08.031"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1039\/B701677H"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajoc.201500444"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.7b00772"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tetlet.2011.03.110"},{"key":"e_1_2_7_36_1","unstructured":"\u00a0"},{"key":"e_1_2_7_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/jhet.5570240357"},{"key":"e_1_2_7_38_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules20058800"},{"key":"e_1_2_7_39_1","unstructured":"\u00a0"},{"key":"e_1_2_7_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tetlet.2009.02.172"},{"key":"e_1_2_7_41_2","doi-asserted-by":"publisher","DOI":"10.1039\/C8RA04576C"},{"key":"e_1_2_7_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2018.06.037"},{"key":"e_1_2_7_43_2","doi-asserted-by":"publisher","DOI":"10.1134\/S1070427211110097"},{"key":"e_1_2_7_44_1","unstructured":"P.\u2005M.\u2005P. Breslow J. L Selnick H. Egbertson M.; The Rockefeller University. USA. Aminotriazole immunomodulators for treating autoimmune diseases. WO2017123518. 2107."},{"key":"e_1_2_7_45_1","unstructured":"\u00a0"},{"key":"e_1_2_7_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/0049-3848(87)90308-2"},{"key":"e_1_2_7_47_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00833a063"},{"key":"e_1_2_7_48_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm981062r"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1021\/op049951d"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1107\/S2053273314026370"},{"key":"e_1_2_7_51_1","first-page":"71","author":"Sheldrick G. M.","year":"2015","journal-title":"Acta Crystallogr C Struct Chem"}],"container-title":["ChemMedChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.202100431","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cmdc.202100431","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.202100431","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T19:49:29Z","timestamp":1760298569000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cmdc.202100431"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,4]]},"references-count":51,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2021,12,14]]}},"alternative-id":["10.1002\/cmdc.202100431"],"URL":"https:\/\/doi.org\/10.1002\/cmdc.202100431","archive":["Portico"],"relation":{},"ISSN":["1860-7179","1860-7187"],"issn-type":[{"value":"1860-7179","type":"print"},{"value":"1860-7187","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,4]]},"assertion":[{"value":"2021-06-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-08-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}