{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T17:01:30Z","timestamp":1790010090315,"version":"4.0.1"},"reference-count":18,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Clausthal University of Technology","id":[{"id":"https:\/\/ror.org\/04qb8nc58","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>A new synthetic strategy for pyrazolo[1,5-d][1,2,4]triazin-7(6H)-ones 4 through intramolecular cyclization of alkyl 2-(4-nitro-1H-pyrazol-3-yl)methylene)hydrazine-1-carboxylates 3 is described, allowing us to selectively modify the N-substituent in 3-position. The reduction in nitro compounds 4 with tin(II) chloride leads to amines 5, and their acetylation leads to acetamides 6. Via alkylation of 4 with bromoacetic acid alkyl esters and 2-chloro-5-(chloromethyl)pyridine, and the subsequent reduction in alkylated nitro compounds 7, the corresponding amines 8 and amides 9 were accessible in very good yields. The molecular structure of ethyl 2-(2-morpholino-3-nitro-7-oxopyrazolo[1,5-d][1,2,4]triazin-6(7H)-yl)acetate (7b) was confirmed by single-crystal X-Ray diffraction analysis. Antibacterial and cytotoxic properties were evaluated for 61 synthesized compounds.<\/jats:p>","DOI":"10.3390\/molecules30183792","type":"journal-article","created":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T12:24:25Z","timestamp":1758198265000},"page":"3792","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Synthesis and Microbiological Activities of 3-Nitropyrazolo-[1,5-d][1,2,4]triazin-7(6H)-ones and Derivatives"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5477-8702","authenticated-orcid":false,"given":"Viktor A.","family":"Zapol\u2019skii","sequence":"first","affiliation":[{"name":"Institute of Organic Chemistry, Clausthal University of Technology, Leibnizstra\u00dfe 6, 38678 Clausthal-Zellerfeld, Germany"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2647-5954","authenticated-orcid":false,"given":"Diana C.","family":"Munoz Castillo","sequence":"additional","affiliation":[{"name":"Helmholtz Centre for Infection Research (HZI), Inhoffenstra\u00dfe 7, 38124 Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Brigitte","family":"Pawletta","sequence":"additional","affiliation":[{"name":"Helmholtz Centre for Infection Research (HZI), Inhoffenstra\u00dfe 7, 38124 Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2952-1208","authenticated-orcid":false,"given":"Ursula","family":"Bilitewski","sequence":"additional","affiliation":[{"name":"Helmholtz Centre for Infection Research (HZI), Inhoffenstra\u00dfe 7, 38124 Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Mimoza","family":"Gjikaj","sequence":"additional","affiliation":[{"name":"Institute of Inorganic and Analytical Chemistry, Clausthal University of Technology, Paul-Ernst-Stra\u00dfe 4, 38678 Clausthal-Zellerfeld, Germany"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Christoff","family":"Br\u00fcdigam","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry, Clausthal University of Technology, Leibnizstra\u00dfe 6, 38678 Clausthal-Zellerfeld, Germany"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9790-828X","authenticated-orcid":false,"given":"Dieter E.","family":"Kaufmann","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry, Clausthal University of Technology, Leibnizstra\u00dfe 6, 38678 Clausthal-Zellerfeld, Germany"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1070\/RC1997v066n10ABEH000310","article-title":"Nitrobutadienes and their halogen derivatives: Synthesis and reactions","volume":"66","author":"Kaberdin","year":"1997","journal-title":"Russ. Chem. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Zapol\u2019skii, V.A., Bilitewski, U., Kupiec, S.R., Ramming, I., and Kaufmann, D.E. (2020). Polyhalonitrobutadienes as Versatile Building Blocks for the Biotargeted Synthesis of Substituted N-Heterocyclic Compounds. Molecules, 25.","DOI":"10.3390\/molecules25122863"},{"key":"ref_3","unstructured":"(2025, August 19). SciFinder\u00ae\u2014A Database of Chemical and Bibliographic Information, a Product of CAS\u2014Columbus, Ohio, United States. Available online: https:\/\/scifinder.cas.org."},{"key":"ref_4","first-page":"997","article-title":"1H-pyrazolo [2,3-d][1,2,4]triazine-3,7-diones as a new class of human leukocyte elastase inhibitors","volume":"49","author":"Baraldi","year":"1999","journal-title":"Arzneim. Forsch."},{"key":"ref_5","unstructured":"Walensky, L.D. (2013). Pyrazol-3-Ones that Activate Pro-Apoptotic. (WO2013055949), BAX. Patent."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/0092-8674(93)90509-O","article-title":"Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programed cell death","volume":"74","author":"Oltvai","year":"1993","journal-title":"Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1021\/jo00155a028","article-title":"1,3-Dipolar cycloaddition reactions of diazopyrazolinones with electron-deficient dipolarophiles","volume":"48","author":"Padwa","year":"1983","journal-title":"J. Org. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"5969","DOI":"10.1016\/j.tet.2012.05.062","article-title":"1,3-Dipolar cycloaddition reaction of 3-trifluoromethyl-4-diazopyrazolinones with acetylenedicarboxylates","volume":"68","author":"Zhang","year":"2012","journal-title":"Tetrahedron"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1515\/znb-2010-0710","article-title":"Chemistry of Polyhalogenated Nitrobutadienes, Part 9: Acyclic and Heterocyclic Nitroenamines and Nitroimines from 2-Nitroperchlorobuta-1,3-diene","volume":"65","author":"Namyslo","year":"2010","journal-title":"Z. Fur Naturforschung Sect. B A J. Chem. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.3762\/bjoc.10.170","article-title":"Efficient synthesis of functionalized (Z)-2-allylidenethiazolidin-4-ones","volume":"10","author":"Namyslo","year":"2014","journal-title":"Beilstein J. Org. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.jbiotec.2016.06.021","article-title":"Screening and characterization of molecules that modulate the biological activity of IFNs-I","volume":"233","author":"Hinkelmann","year":"2016","journal-title":"J. Biotechnol."},{"key":"ref_12","unstructured":"(2025, February 12). Available online: https:\/\/www.periodensystem-online.de\/index.php?sel=wertdesc&prop=pKb-Werte&show=list&el=92&id=-acid."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6093","DOI":"10.1021\/ja900450h","article-title":"Identification of an imino group indispensable for cleavage by a small ribozyme","volume":"131","author":"Spitale","year":"2009","journal-title":"J. Am. Chem. Soc."},{"key":"ref_14","first-page":"68","article-title":"Nitration of 2-H-pentachloro-1,3-butadiene","volume":"40","author":"Potkin","year":"1996","journal-title":"Dokl. Natl. Acad. Sci. Belarus"},{"key":"ref_15","first-page":"981","article-title":"Reaction of 2-nitropentachloro-1,3-butadiene with secondary amines","volume":"15","author":"Kaberdin","year":"1979","journal-title":"J. Org. Chem. USSR Engl. Transl."},{"key":"ref_16","first-page":"39","article-title":"Reaction of 2-nitropentachloro-1,3-butadiene with primary amines","volume":"15","author":"Kaberdin","year":"1979","journal-title":"J. Org. Chem. USSR Engl. Transl."},{"key":"ref_17","first-page":"11989","article-title":"Synthesis of new types of compounds modulating the biological activity of Type I Interferons (IFN-I)","volume":"2023","author":"Oggero","year":"2023","journal-title":"Arkivoc"},{"key":"ref_18","first-page":"3","article-title":"Crystal structure refinement with SHELXL","volume":"71","author":"Sheldrick","year":"2015","journal-title":"Acta Crystallogr."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/18\/3792\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:07:20Z","timestamp":1790006840000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/18\/3792"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,18]]},"references-count":18,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["molecules30183792"],"URL":"https:\/\/doi.org\/10.3390\/molecules30183792","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,18]]}}}