{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T01:15:22Z","timestamp":1783473322604,"version":"3.55.0"},"reference-count":60,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,10]],"date-time":"2021-12-10T00:00:00Z","timestamp":1639094400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001823","name":"Ministry of Education Youth and Sports","doi-asserted-by":"publisher","award":["21-SVV\/2018"],"award-info":[{"award-number":["21-SVV\/2018"]}],"id":[{"id":"10.13039\/501100001823","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001823","name":"Ministry of Education Youth and Sports","doi-asserted-by":"publisher","award":["LM2018130"],"award-info":[{"award-number":["LM2018130"]}],"id":[{"id":"10.13039\/501100001823","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ERDF\/ESF","award":["CZ.02.1.01\/0.0\/0.0\/16_025\/0007444"],"award-info":[{"award-number":["CZ.02.1.01\/0.0\/0.0\/16_025\/0007444"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Kynurenic acid is a neuroprotective metabolite of tryptophan formed by kynurenine aminotransferase (KAT) catalyzed transformation of kynurenine. However, its high brain levels are associated with cognitive deficit and with the pathophysiology of schizophrenia. Although several classes of KAT inhibitors have been published, the search for new inhibitor chemotypes is crucial for the process of finding suitable clinical candidates. Therefore, we used pharmacophore modeling and molecular docking, which predicted derivatives of heterocyclic amino ketones as new potential irreversible inhibitors of kynurenine aminotransferase II. Thiazole and triazole-based amino ketones were synthesized within a SAR study and their inhibitory activities were evaluated in vitro. The observed activities confirmed our computational model and, moreover, the best compounds showed sub-micromolar inhibitory activity with 2-alaninoyl-5-(4-fluorophenyl)thiazole having IC50 = 0.097 \u00b5M.<\/jats:p>","DOI":"10.3390\/ph14121291","type":"journal-article","created":{"date-parts":[[2021,12,10]],"date-time":"2021-12-10T08:17:58Z","timestamp":1639124278000},"page":"1291","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Heterocyclic Cathinones as Inhibitors of Kynurenine Aminotransferase II\u2014Design, Synthesis, and Evaluation"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9593-9472","authenticated-orcid":false,"given":"Michal","family":"Mary\u0161ka","sequence":"first","affiliation":[{"name":"Forensic Laboratory of Biologically Active Substances, Department of Chemistry of Natural Compounds, Faculty of Food and Biochemical Technology, University of Chemistry and Technology Prague, Technick\u00e1 5, 16628 Prague, Czech Republic"},{"name":"National Institute of Mental Health, Topolov\u00e1 748, 250 67 Klecany, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4316-1560","authenticated-orcid":false,"given":"Lucie","family":"Svobodov\u00e1","sequence":"additional","affiliation":[{"name":"Forensic Laboratory of Biologically Active Substances, Department of Chemistry of Natural Compounds, Faculty of Food and Biochemical Technology, University of Chemistry and Technology Prague, Technick\u00e1 5, 16628 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6979-5508","authenticated-orcid":false,"given":"Wim","family":"Dehaen","sequence":"additional","affiliation":[{"name":"CZ-OPENSCREEN: National Infrastructure for Chemical Biology, Department of Informatics and Chemistry, Faculty of Chemical Technology, University of Chemistry and Technology Prague, Technick\u00e1 5, 16628 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9428-4109","authenticated-orcid":false,"given":"Martina","family":"Hrabinov\u00e1","sequence":"additional","affiliation":[{"name":"Biomedical Research Center, University Hospital Hradec Kr\u00e1lov\u00e9, Sokolsk\u00e1 581, 50005 Hradec Kralov\u00e9, Czech Republic"},{"name":"Department of Toxicology and Military Pharmacy, University of Defense, T\u0159ebe\u0161sk\u00e1 1575, 50005 Hradec Kr\u00e1lov\u00e9, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5645-8227","authenticated-orcid":false,"given":"Michaela","family":"Rumlov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Faculty of Food and Biochemical Technology, University of Chemistry and Technology Prague, Technick\u00e1 5, 16628 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6376-8701","authenticated-orcid":false,"given":"Ond\u0159ej","family":"Soukup","sequence":"additional","affiliation":[{"name":"Biomedical Research Center, University Hospital Hradec Kr\u00e1lov\u00e9, Sokolsk\u00e1 581, 50005 Hradec Kralov\u00e9, Czech Republic"},{"name":"Department of Toxicology and Military Pharmacy, University of Defense, T\u0159ebe\u0161sk\u00e1 1575, 50005 Hradec Kr\u00e1lov\u00e9, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3390-5650","authenticated-orcid":false,"given":"Martin","family":"Kucha\u0159","sequence":"additional","affiliation":[{"name":"Forensic Laboratory of Biologically Active Substances, Department of Chemistry of Natural Compounds, Faculty of Food and Biochemical Technology, University of Chemistry and Technology Prague, Technick\u00e1 5, 16628 Prague, Czech Republic"},{"name":"National Institute of Mental Health, Topolov\u00e1 748, 250 67 Klecany, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/0304-3940(84)90050-8","article-title":"Kynurenic acid blocks neurotoxicity and seizures induced in rats by the related brain metabolite quinolinic acid","volume":"48","author":"Foster","year":"1984","journal-title":"Neurosci. Lett."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1111\/j.1476-5381.1991.tb12274.x","article-title":"A comparison of excitotoxic lesions of the basal forebrain by kainate, quinolinate, ibotenate, N-methyl-d-aspartate or quisqualate, and the effects on toxicity of 2-amino-5-phosphonovaleric acid and kynurenic acid in the rat","volume":"102","author":"Winn","year":"1991","journal-title":"Br. J. Pharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1038\/nrn3257","article-title":"Kynurenines in the mammalian brain: When physiology meets pathology","volume":"13","author":"Schwarcz","year":"2012","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.tips.2020.11.006","article-title":"Tryptophan Metabolism as a Pharmacological Target","volume":"42","author":"Modoux","year":"2021","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1177\/0269881106073126","article-title":"Review: Glutamate and dopamine dysregulation in schizophrenia\u2014A synthesis and selective review","volume":"21","author":"Stone","year":"2007","journal-title":"J. Psychopharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1093\/schbul\/sbw221","article-title":"Kynurenic Acid in Schizophrenia: A Systematic Review and Meta-analysis","volume":"43","author":"Plitman","year":"2017","journal-title":"Schizophr. Bull."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/S0304-3940(01)02242-X","article-title":"Kynurenic acid levels ae elevated in the cerebrospinal fluid of patients with schizophrenia","volume":"313","author":"Erhardt","year":"2001","journal-title":"Neurosci. Lett."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/S0006-3223(01)01078-2","article-title":"Increased cortical kynurenate content in schizophrenia","volume":"50","author":"Schwarcz","year":"2001","journal-title":"Biol. Psychiatry"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/hipo.23040","article-title":"Inhibition of kynurenine aminotransferase II attenuates hippocampus-dependent memory deficit in adult rats treated prenatally with kynurenine","volume":"29","author":"Pocivavsek","year":"2019","journal-title":"Hippocampus"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1007\/s40495-019-00208-2","article-title":"Neuropathology of Kynurenine Pathway of Tryptophan Metabolism","volume":"6","author":"Tutakhail","year":"2020","journal-title":"Curr. Pharmacol. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2860","DOI":"10.1038\/s41380-019-0401-9","article-title":"Dysregulation of kynurenine metabolism is related to proinflammatory cytokines, attention, and prefrontal cortex volume in schizophrenia","volume":"25","author":"Kindler","year":"2020","journal-title":"Mol. Psychiatry"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/1178646917691938","article-title":"Kynurenine Pathway of Tryptophan Metabolism: Regulatory and Functional Aspects","volume":"10","author":"Badawy","year":"2017","journal-title":"Int. J. Tryptophan Res."},{"key":"ref_13","first-page":"423","article-title":"Astrocytes as Pharmacological Targets in the Treatment of Schizophrenia: Focus on Kynurenic Acid","volume":"Volume 23","author":"Pletnikov","year":"2016","journal-title":"Modeling the Psychopathological Dimensions of Schizophrenia"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Fukuwatari, T. (2020). Possibility of Amino Acid Treatment to Prevent the Psychiatric Disorders via Modulation of the Production of Tryptophan Metabolite Kynurenic Acid. Nutrients, 12.","DOI":"10.3390\/nu12051403"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.1038\/npp.2010.39","article-title":"Reduction of Endogenous Kynurenic Acid Formation Enhances Extracellular Glutamate, Hippocampal Plasticity, and Cognitive Behavior","volume":"35","author":"Potter","year":"2010","journal-title":"Neuropsychopharmacology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5684","DOI":"10.1021\/jm100464k","article-title":"Crystal structure-based selective targeting of the pyridoxal 5\u2019-phosphate dependent enzyme kynurenine aminotransferase II for cognitive enhancement","volume":"53","author":"Rossi","year":"2010","journal-title":"J. Med. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1002\/cmdc.200800109","article-title":"Sequence Variants in Kynurenine Aminotransferase II (KAT II) Orthologs Determine Different Potencies of the Inhibitor S-ESBA","volume":"3","author":"Pellicciari","year":"2008","journal-title":"ChemMedChem"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1002\/cmdc.200500095","article-title":"Modulators of the Kynurenine Pathway of Tryptophan Metabolism: Synthesis and Preliminary Biological Evaluation of (S)-4-(Ethylsulfonyl)benzoylalanine, a Potent and Selective Kynurenine Aminotransferase II (KAT II) Inhibitor","volume":"1","author":"Pellicciari","year":"2006","journal-title":"ChemMedChem"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1021\/ml200204m","article-title":"Discovery of Brain-Penetrant, Irreversible Kynurenine Aminotransferase II Inhibitors for Schizophrenia","volume":"3","author":"Dounay","year":"2012","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/11786469211041368","article-title":"Blockade of KAT II Facilitates LTP in Kynurenine 3-Monooxygenase Depleted Mice","volume":"14","author":"Imbeault","year":"2021","journal-title":"Int. J. Tryptophan Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.neuropharm.2014.03.004","article-title":"A systemically-available kynurenine aminotransferase II (KAT II) inhibitor restores nicotine-evoked glutamatergic activity in the cortex of rats","volume":"82","author":"Gritton","year":"2014","journal-title":"Neuropharmacology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.neuropharm.2015.10.028","article-title":"Inhibition of kynurenine aminotransferase II reduces activity of midbrain dopamine neurons","volume":"102","author":"Linderholm","year":"2016","journal-title":"Neuropharmacology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.brainresbull.2018.12.014","article-title":"Investigating KYNA production and kynurenergic manipulation on acute mouse brain slice preparations","volume":"146","author":"Cseh","year":"2019","journal-title":"Brain Res. Bull."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1002\/jnr.24489","article-title":"Modification of kynurenine pathway via inhibition of kynurenine hydroxylase attenuates surgical brain injury complications in a male rat model","volume":"98","author":"Zakhary","year":"2020","journal-title":"J. Neurosci. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.bbrc.2019.11.130","article-title":"A covalent small molecule inhibitor of glutamate-oxaloacetate transaminase 1 impairs pancreatic cancer growth","volume":"522","author":"Yoshida","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1007\/s00213-020-05507-x","article-title":"Stress-induced impairment in fear discrimination is causally related to increased kynurenic acid formation in the prefrontal cortex","volume":"237","author":"Klausing","year":"2020","journal-title":"Psychopharmacology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"10592","DOI":"10.1523\/JNEUROSCI.1107-14.2014","article-title":"Reduction of Brain Kynurenic Acid Improves Cognitive Function","volume":"34","author":"Kozak","year":"2014","journal-title":"J. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1039\/C2MD20166F","article-title":"Discovery of hydroxamate bioisosteres as KAT II inhibitors with improved oral bioavailability and pharmacokinetics","volume":"4","author":"Henderson","year":"2013","journal-title":"Med. Chem. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1021\/ml300237v","article-title":"Structure-Based Design of Irreversible Human KAT II Inhibitors: Discovery of New Potency-Enhancing Interactions","volume":"4","author":"Tuttle","year":"2013","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_30","unstructured":"Claffey, M.M., Dounay, A.B., Gan, X., Hayward, M.M., Rong, S., Tuttle, J.B., and Verhoest, P.R. (2010). Bicyclic and Tricyclic Compounds as KAT II Inhibitors. (2010\/146488A1), WO Patent."},{"key":"ref_31","unstructured":"Dounay, A.B., McAllister, L.A., Parikh, V.D., Rong, S., and Verhoest, P.R. (2012). KAT II Inhibitors. (2012\/073143A1), WO Patent."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1016\/j.bmcl.2013.02.039","article-title":"PF-04859989 as a template for structure-based drug design: Identification of new pyrazole series of irreversible KAT II inhibitors with improved lipophilic efficiency","volume":"23","author":"Dounay","year":"2013","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_33","unstructured":"Dounay, A.B., Tuttle, J.B., and Verhoest, P.R. (2013). Preparation of Tricyclic Compounds as KAT II Inhibitors. (2013\/186666A1), WO Patent."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"S152","DOI":"10.1093\/schbul\/sbt157","article-title":"Targeting Kynurenine Aminotransferase II in Psychiatric Diseases: Promising Effects of an Orally Active Enzyme Inhibitor","volume":"40","author":"Wu","year":"2014","journal-title":"Schizophr. Bull."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"10243","DOI":"10.1038\/s41598-019-46666-y","article-title":"Selective and competitive inhibition of kynurenine aminotransferase 2 by glycyrrhizic acid and its analogues","volume":"9","author":"Yoshida","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Jayawickrama, G.S., Nematollahi, A., Sun, G., and Church, W.B. (2018). Improvement of kynurenine aminotransferase-II inhibitors guided by mimicking sulfate esters. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0196404"},{"key":"ref_37","unstructured":"Okuyama, M., Fukunaga, K., Usui, K., Hayashi, N., Iijima, D., Horiuchi, H., and Itagaki, N. (2015). Novel Bicyclic or Tricyclic Heterocyclic Compounds and Their Pharmaceutical Compositions for Prophylactic and Therapeutic Treatment of KAT (Kynurenine Aminotransferase) II-Associated Disorders. (2015\/163339A1), WO Patent."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"127060","DOI":"10.1016\/j.bmcl.2020.127060","article-title":"Discovery of sulfonamides and 9-oxo-2,8-diazaspiro[5,5]undecane-2-carboxamides as human kynurenine aminotransferase 2 (KAT2) inhibitors","volume":"30","author":"Kalliokoski","year":"2020","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2665","DOI":"10.1021\/ol020092s","article-title":"A practical approach to the synthesis of 2,4-disubstituted oxazoles from amino acids","volume":"4","author":"Morwick","year":"2002","journal-title":"Org. Lett."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1002\/hlca.200690010","article-title":"Transformation of amino acids into nonracemic 1-(heteroaryl)ethanamines by the enamino ketone methodology","volume":"89","author":"Pirc","year":"2006","journal-title":"Helv. Chim. Acta"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"8223","DOI":"10.1016\/S0040-4039(02)02031-2","article-title":"Improved syntheses of \u03b1-BOC-aminoketones from \u03b1-BOC-amino-Weinreb amides using a pre-deprotonation protocol","volume":"43","author":"Liu","year":"2002","journal-title":"Tetrahedron Lett."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1021\/ja0471525","article-title":"Copper(I)-catalyzed synthesis of azoles. DFT study predicts unprecedented reactivity and intermediates","volume":"127","author":"Himo","year":"2005","journal-title":"J. Am. Chem. Soc."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Andersen, J., Madsen, U., Bj\u00f6rkling, F., and Liang, X. (2005). Rapid Synthesis of Aryl Azides from Aryl Halides under Mild Conditions. Synlett, 2209\u20132213.","DOI":"10.1055\/s-2005-872248"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3676","DOI":"10.1021\/ol501458p","article-title":"Oxidative Esterification of Aldehydes Using Mesoionic 1,2,3-Triazolyl Carbene Organocatalysts","volume":"16","author":"Berry","year":"2014","journal-title":"Org. Lett."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3704","DOI":"10.1021\/ol501514b","article-title":"Synthesis of 3-pyrrolin-2-ones by rhodium-catalyzed transannulation of 1-sulfonyl-1,2,3-triazole with ketene silyl acetal","volume":"16","author":"Ran","year":"2014","journal-title":"Org. Lett."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4397","DOI":"10.1039\/c4ob00515e","article-title":"A reagent for safe and efficient diazo-transfer to primary amines: 2-azido-1,3-dimethylimidazolinium hexafluorophosphate","volume":"12","author":"Kitamura","year":"2014","journal-title":"Org. Biomol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5836","DOI":"10.1021\/acs.orglett.7b02806","article-title":"Rapid Access to a Broad Range of 6\u2032-Substituted Firefly Luciferin Analogues Reveals Surprising Emitters and Inhibitors","volume":"19","author":"Sharma","year":"2017","journal-title":"Org. Lett."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1248\/cpb.46.623","article-title":"Synthesis and Antifungal Activity of Novel Thiazole-Containing Triazole Antifungals. II. Optically Active ER-30346 and Its Derivatives","volume":"46","author":"Tsuruoka","year":"1998","journal-title":"Chem. Pharm. Bull."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1021\/acs.joc.9b02803","article-title":"Synthesis of Tetrasubstituted Thiophenes via Direct Metalation","volume":"85","author":"Janeba","year":"2020","journal-title":"J. Org. Chem."},{"key":"ref_50","unstructured":"(2021). Molecular Operating Environment (MOE), 2019.01, Chemical Computing Group ULC."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.ab.2016.02.003","article-title":"Development of a RapidFire mass spectrometry assay and a fluorescence assay for the discovery of kynurenine aminotransferase II inhibitors to treat central nervous system disorders","volume":"501","author":"Lu","year":"2016","journal-title":"Anal. Biochem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2483","DOI":"10.1002\/chem.202004468","article-title":"Probing \u03b1-Amino Aldehydes as Weakly Acidic Pronucleophiles: Direct Access to Quaternary \u03b1-Amino Aldehydes by an Enantioselective Michael Addition Catalyzed by Br\u00f8nsted Bases","volume":"27","author":"Mielgo","year":"2021","journal-title":"Chem. \u2013 A Eur. J."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3453","DOI":"10.1021\/ol101252y","article-title":"Total Synthesis of Syringolin A","volume":"12","author":"Dai","year":"2010","journal-title":"Org. Lett."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"82","DOI":"10.3184\/174751916X14539789662063","article-title":"An Efficient Preparation of Novel Epoxyketone Intermediates for the Synthesis of Carfilzomib and Its Derivatives","volume":"40","author":"Du","year":"2016","journal-title":"J. Chem. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1021\/acs.jmedchem.7b01690","article-title":"Discovery of a Novel Oral Glucocorticoid Receptor Modulator (AZD9567) with Improved Side Effect Profile","volume":"61","author":"Ripa","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_56","first-page":"282","article-title":"Diastereoselective Synthesis of N-Protected \u03b2-Amino-\u03b1-Hydroxyacids (Norstatines) from Urethane N-Carboxyanhydrides (UNCAs)","volume":"4","author":"Audin","year":"1999","journal-title":"J. Chem. Res. Synopses"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"5614","DOI":"10.1021\/jo900693a","article-title":"Synthesis of Substituted Pyrrolin-4-Ones from Amino Acids in Mild Conditions via a Gold-Catalyzed Approach","volume":"74","author":"Gouault","year":"2009","journal-title":"J. Org. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"9670","DOI":"10.1021\/acs.orglett.0c03732","article-title":"Divergent Strategies for the \u03c0-Extension of Heteroaryl Halides Using Norbornadiene as an Acetylene Synthon","volume":"22","author":"Jeong","year":"2020","journal-title":"Org. Lett."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.1002\/cmdc.201000265","article-title":"\u03b1-Ketoheterocycles as Inhibitors of Leishmania Mexicana Cysteine Protease CPB","volume":"5","author":"Steert","year":"2010","journal-title":"ChemMedChem"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1016\/j.tetlet.2019.05.043","article-title":"A Convenient Synthesis of 2-Acyl Benzothiazoles\/Thiazoles from Benzothiazole\/Thiazole and N,N\u2019-Carbonyldiimidazole Activated Carboxylic Acids","volume":"60","author":"Huang","year":"2019","journal-title":"Tetrahedron Lett."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/14\/12\/1291\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:45:04Z","timestamp":1760168704000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/14\/12\/1291"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,10]]},"references-count":60,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["ph14121291"],"URL":"https:\/\/doi.org\/10.3390\/ph14121291","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,10]]}}}