{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T11:39:02Z","timestamp":1776166742133,"version":"3.50.1"},"reference-count":53,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Federal Program","award":["No.125020601629-0"],"award-info":[{"award-number":["No.125020601629-0"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Multicomponent reactions with isocyanides (IMCRs) enable the one-step assembly of complex molecules and remain a powerful strategy for accessing bioactive scaffolds. Here, we report the first synthesis of an abietane diterpene isocyanide derived from aminoimide methyl maleopimarate 1, a levopimaric acid-maleic anhydride adduct. This isocyanide was further engaged in Passerini, Ugi, and azido-Ugi reactions to provide a series of \u03b1-acyloxy- and \u03b1-acylaminocarboxamides, as well as tetrazoles, in high yields under optimized conditions. The structures of all products were confirmed by comprehensive physicochemical analysis. In silico ADME, drug-likeness, target prediction, and toxicity studies (SwissADME, ProTox-III) revealed moderate lipophilicity with favorable membrane permeability and solubility, high gastrointestinal absorption, and selective CYP3A4 inhibition with no significant effects on other CYP450 isoforms. The compounds fulfill major drug-likeness criteria, lacking undesirable reactive fragments, with only acceptable deviations in molecular weight and flexibility typical for MCR-derived products. The modifications broaden the spectrum of predicted biological targets while maintaining low overall toxicity and absence of predicted hepato- or carcinogenicity. These results demonstrate that diterpene isocyanide is a valuable building block for chemical libraries of structurally diverse abietane derivatives with peptide-like termini and highlight its potential as a source of cytotoxic, antiviral, and anti-inflammatory candidates.<\/jats:p>","DOI":"10.3390\/ijms27083494","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T10:29:08Z","timestamp":1776162548000},"page":"3494","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A First Diversity-Oriented N-Maleopimarimido-Isocyanide for Multicomponent Reactions: Synthesis, Application, and In Silico Evaluation"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0693-220X","authenticated-orcid":false,"given":"Elena","family":"Tretyakova","sequence":"first","affiliation":[{"name":"Ufa Institute of Chemistry, Ufa Federal Research Centre, Russian Academy of Sciences, 71 Prosp. Oktyabrya, Ufa 450054, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2185-6492","authenticated-orcid":false,"given":"Anna","family":"Smirnova","sequence":"additional","affiliation":[{"name":"Ufa Institute of Chemistry, Ufa Federal Research Centre, Russian Academy of Sciences, 71 Prosp. Oktyabrya, Ufa 450054, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5606-1588","authenticated-orcid":false,"given":"Oxana","family":"Kazakova","sequence":"additional","affiliation":[{"name":"Ufa Institute of Chemistry, Ufa Federal Research Centre, Russian Academy of Sciences, 71 Prosp. Oktyabrya, Ufa 450054, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Graziano, G., Stefanachi, A., Contino, M., Prieto-D\u00edaz, R., Ligresti, A., Kumar, P., Scilimati, A., Sotelo, E., and Leonetti, F. (2023). Multicomponent Reaction-Assisted Drug Discovery: A Time- and Cost-Effective Green Approach Speeding Up Identification and Optimization of Anticancer Drugs. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24076581"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1002\/anie.198208101","article-title":"From isocyanides via four component condensations to antibiotic syntheses","volume":"21","author":"Ugi","year":"1982","journal-title":"Angew. Chem. Int. Ed. 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