{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T23:25:02Z","timestamp":1790378702889,"version":"4.1.0"},"reference-count":167,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T00:00:00Z","timestamp":1765238400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22361132526"],"award-info":[{"award-number":["22361132526"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["24-43-00003"],"award-info":[{"award-number":["24-43-00003"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This work aimed to synthesize new derivatives of 2-hydrazinylpyridine-3-carbonitrile and to investigate their biological activity as safeners for the 2,4-D herbicide. The new 2-hydrazinylnicotinonitriles were obtained in high yields (up to quantitative) under mild conditions (25 \u00b0C, dioxane) by treating 4,6-diaryl-2-bromo-3-cyanopyridines with hydrazine hydrate. The latter were synthesized by brominating 2-(3-oxo-1,3-diarylpropyl)malononitriles, the Michael adducts, which are readily available from 1,3-diarylpropenones (chalcones) and malononitrile. An unusual side product of the bromination\/carbocyclization was isolated and characterized; it consisted of co-crystals of 3-benzoyl-4-hydroxy-4-phenyl-2,6-di-(p-tolyl)cyclohexane-1,1-dicarbonitrile and 3-benzoyl-5-bromo-4-hydroxy-4-phenyl-2,6-di-(p-tolyl)cyclohexane-1,1-dicarbonitrile at a ~4:6 ratio. The new 2-hydrazinylnicotinonitriles react with halogen-containing aromatic aldehydes to form the corresponding hydrazones. The biological activity of the new nicotinonitriles was examined for their function as 2,4-D antidotes. It was found that, under laboratory conditions, eight of the synthesized compounds exhibited a notable antidote effect against 2,4-D on sunflower seedlings.<\/jats:p>","DOI":"10.3390\/ijms262411874","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T12:42:43Z","timestamp":1765284163000},"page":"11874","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Synthesis, Reactions, and Agrochemical Studies of New 4,6-Diaryl-2-hydrazinylnicotinonitriles"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7163-0497","authenticated-orcid":false,"given":"Victor V.","family":"Dotsenko","sequence":"first","affiliation":[{"name":"Department of Organic Chemistry and Technologies, Kuban State University, 149 Stavropolskaya St., 350040 Krasnodar, Russia"},{"name":"Department of Chemistry, North Caucasus Federal University, 1a Pushkin St., 355017 Stavropol, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9960-9440","authenticated-orcid":false,"given":"Vladislav K.","family":"Kindop","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry and Technologies, Kuban State University, 149 Stavropolskaya St., 350040 Krasnodar, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9005-9668","authenticated-orcid":false,"given":"Vyacheslav K.","family":"Kindop","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry and Technologies, Kuban State University, 149 Stavropolskaya St., 350040 Krasnodar, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renat G.","family":"Achmiz","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry and Technologies, Kuban State University, 149 Stavropolskaya St., 350040 Krasnodar, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4787-7072","authenticated-orcid":false,"given":"Arina G.","family":"Levchenko","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry and Technologies, Kuban State University, 149 Stavropolskaya St., 350040 Krasnodar, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5581-0241","authenticated-orcid":false,"given":"Polina G.","family":"Dakhno","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry and Technologies, Kuban State University, 149 Stavropolskaya St., 350040 Krasnodar, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8048-4740","authenticated-orcid":false,"given":"Azamat Z.","family":"Temerdashev","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Kuban State University, 149 Stavropolskaya St., 350040 Krasnodar, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1107-5385","authenticated-orcid":false,"given":"Yu-Qi","family":"Feng","sequence":"additional","affiliation":[{"name":"School of Bioengineering and Health, Wuhan Textile University, 1 Sunshine Avenue, Jiang Xia District, Wuhan 430200, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1539-0227","authenticated-orcid":false,"given":"Quan-Fei","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Bioengineering and Health, Wuhan Textile University, 1 Sunshine Avenue, Jiang Xia District, Wuhan 430200, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8244-5925","authenticated-orcid":false,"given":"Eva S.","family":"Daus","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry and Technologies, Kuban State University, 149 Stavropolskaya St., 350040 Krasnodar, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3435-4873","authenticated-orcid":false,"given":"Igor V.","family":"Yudaev","sequence":"additional","affiliation":[{"name":"Faculty of Energetics, Kuban State Agrarian University, 13 Kalinina St., 350044 Krasnodar, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9120-7637","authenticated-orcid":false,"given":"Yuliia V.","family":"Daus","sequence":"additional","affiliation":[{"name":"Faculty of Energetics, Kuban State Agrarian University, 13 Kalinina St., 350044 Krasnodar, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6644-9949","authenticated-orcid":false,"given":"Alexander V.","family":"Aksenov","sequence":"additional","affiliation":[{"name":"Department of Chemistry, North Caucasus Federal University, 1a Pushkin St., 355017 Stavropol, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7125-9066","authenticated-orcid":false,"given":"Nicolai A.","family":"Aksenov","sequence":"additional","affiliation":[{"name":"Department of Chemistry, North Caucasus Federal University, 1a Pushkin St., 355017 Stavropol, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8083-1407","authenticated-orcid":false,"given":"Inna V.","family":"Aksenova","sequence":"additional","affiliation":[{"name":"Department of Chemistry, North Caucasus Federal University, 1a Pushkin St., 355017 Stavropol, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1023\/A:1023954524573","article-title":"Methods for the synthesis of hydrazinylpyridines and some of their characteristics. (review)","volume":"39","author":"Kobrakov","year":"2003","journal-title":"Chem. Heterocycl. Compd."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Flefel, E.M., El-Sofany, W.I., El-Shahat, M., Naqvi, A., and Assirey, E. (2018). Synthesis, molecular docking and in vitro screening of some newly synthesized triazolopyridine, pyridotriazine and pyridine\u2013pyrazole hybrid derivatives. Molecules, 23.","DOI":"10.3390\/molecules23102548"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.1134\/S1070363224100050","article-title":"6-(Pyrazol-1-yl)pyrazolo[3,4-b]pyridines: Synthesis, structure, and wheat growth regulating activity","volume":"94","author":"Dmitrieva","year":"2024","journal-title":"Russ. J. Gen. Chem."},{"key":"ref_4","unstructured":"Dyadyuchenko, L.V., Balakhov, A.A., Nazarenko, D.Y., Morozovskij, V.V., and Tkach, L.N. (2017). Method of Increasing Winter Wheat Yield. (Patent RU 2623115)."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.molstruc.2018.04.010","article-title":"Synthesis, docking, QSAR, ADMET and antimicrobial evaluation of new quinoline-3-carbonitrile derivatives as potential DNA-gyrase inhibitors","volume":"1166","author":"Saad","year":"2018","journal-title":"J. Mol. Struct."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"AbdelHaleem, A., Mansour, A.O., AbdelKader, M., and Arafa, R.K. (2020). Selective VEGFR-2 inhibitors: Synthesis of pyridine derivatives, cytotoxicity and apoptosis induction profiling. Bioorg. Chem., 103.","DOI":"10.1016\/j.bioorg.2020.104222"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Meier, A.A., Moon, H.J., Sabuncu, S., Singh, P., Ronnebaum, T.A., Ou, S., Douglas, J.T., Jackson, T.A., Mo\u00ebnne-Loccoz, P., and Mure, M. (2022). Insight into the spatial arrangement of the lysine tyrosylquinone and Cu2+ in the active site of lysyl oxidase-like 2. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232213966"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Meier, A.A., Kuczera, K., and Mure, M. (2022). A 3D\u2013predicted structure of the amine oxidase domain of lysyl oxidase\u2013like 2. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232113385"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.saa.2015.01.009","article-title":"Tridentate hydrazone metal complexes derived from cephalexin and 2-hydrazinylpyridine: Synthesis, characterization and antibacterial activity","volume":"141","author":"Anacona","year":"2015","journal-title":"Spectrochim. Acta A"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1016\/S0277-5387(00)81394-7","article-title":"Complexes of palladium(II) and platinum(II) with 2-hydrazinylpyridine and 8-hydrazinylquinoline","volume":"5","author":"Edwards","year":"1986","journal-title":"Polyhedron"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1007\/s12039-019-1598-5","article-title":"Rhodium(III) complex with pyrene-pyridyl-hydrazone: Synthesis, structure, ligand redox, spectral characterization and DFT calculation","volume":"131","author":"Dinda","year":"2019","journal-title":"J. Chem. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1134\/S0036023619060020","article-title":"Soluble cytotoxic Ruthenium(II) complexes with 2-Hydrazinylpyridine","volume":"64","author":"Soliman","year":"2019","journal-title":"Russ. J. Inorg. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1007\/s11243-019-00317-3","article-title":"Metal transition complexes of tridentate Schiff base ligands derived from 2-hydrazinylpyridine: Synthesis, spectroscopic characterization and X-ray structures","volume":"44","author":"Diop","year":"2019","journal-title":"Transit. Met. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"132813","DOI":"10.1016\/j.molstruc.2022.132813","article-title":"Dioxomolybdenum (VI) and oxomolybdenum (IV) complexes with N, O, and S bidentate ligands, syntheses, spectral characterization, and DFT studies","volume":"1260","author":"Alajrawy","year":"2022","journal-title":"J. Mol. Struct."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3237","DOI":"10.1021\/ic961489t","article-title":"Synthesis and characterization of Rhenium(III) and Technetium(III) organohydrazide Chelate Complexes. reactions of 2-hydrazinylpyridine with complexes of rhenium and Technetium","volume":"36","author":"Nicholson","year":"1997","journal-title":"Inorg. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s41664-020-00120-5","article-title":"A method for simultaneous determination of 14 carbonyl-steroid hormones in human serum by ultra high performance liquid chromatography\u2013tandem mass spectrometry","volume":"4","author":"Bai","year":"2020","journal-title":"J. Anal. Test."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.clinms.2017.08.001","article-title":"Multiplexed analysis of steroid hormones in saliva by LC-MS\/MS with 2-hydrazinylpyridine derivatization","volume":"4\u20135","author":"Nadarajah","year":"2017","journal-title":"Clin. Mass Spectrom."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.jchromb.2011.01.020","article-title":"Quantification of 2-hydrazinylpyridine derivatized steroid hormones in fathead minnow (Pimephales promelas) blood plasma using LC-ESI+\/MS\/MS","volume":"879","author":"Hala","year":"2011","journal-title":"J. Chromatogr. B"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jchromb.2019.01.022","article-title":"Simultaneous determination of androgens and prostaglandins in human urine using ultra-high-performance liquid chromatography\u2013tandem mass spectrometry","volume":"1109","author":"Im","year":"2019","journal-title":"J. Chromatogr. B"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.steroids.2015.01.019","article-title":"Determination of seven selected neuro- and immunomodulatory steroids in human cerebrospinal fluid and plasma using LC-MS\/MS","volume":"98","author":"Sosvorova","year":"2015","journal-title":"Steroids"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"106080","DOI":"10.1016\/j.neuint.2025.106080","article-title":"LC-MS\/MS techniques for the analysis of steroid panel in human cerebrospinal fluid","volume":"191","author":"Skodova","year":"2025","journal-title":"Neurochem. Int."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"112447","DOI":"10.1016\/j.microc.2024.112447","article-title":"Rapid determination of \u03b1,\u03b2-unsaturated aldehydes in vegetable oils by desorption corona beam ionization-tandem mass spectrometry based on a twin derivatization strategy","volume":"208","author":"Qin","year":"2025","journal-title":"Microchem. J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"7634","DOI":"10.1021\/acs.analchem.4c00527","article-title":"Strategy to empower nontargeted metabolomics by triple-dimensional combinatorial derivatization with MS-TDF Software","volume":"96","author":"Yuan","year":"2024","journal-title":"Anal. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/b101226","article-title":"6-Hydrazinylnicotinamide derivatives as bifunctional coupling agents for 99mTc-labeling of small biomolecules","volume":"252","author":"Liu","year":"2005","journal-title":"Top. Curr. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/s41181-025-00373-4","article-title":"Development and evaluation of a 99mTc-labeled olaparib analog for PARP imaging","volume":"10","author":"Xu","year":"2025","journal-title":"EJNMMI Radiopharm. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"344812","DOI":"10.1016\/j.aca.2025.344812","article-title":"Stimuli-responsive and biocompatible pyridyhydrazone-phenol Schiff base and its Zn(II)-complex: Distinct fluorescent detection of SO42\u2212\/CO32\u2212 in cell lines and real water samples","volume":"1382","author":"Thakur","year":"2025","journal-title":"Anal. Chim. Acta"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"126979","DOI":"10.1016\/j.saa.2025.126979","article-title":"Pyridine-hydrazone-based charge-transfer probe for detecting Cu2+ and Co2+ ions in aqueous solutions","volume":"347","author":"Park","year":"2026","journal-title":"Spectrochim. Acta A"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.snb.2017.01.149","article-title":"A novel diarylethene-hydrazinylpyridine-based probe for fluorescent detection of aluminum ion and naked-eye detection of hydroxide ion","volume":"245","author":"Li","year":"2017","journal-title":"Sens. Actuators B Chem."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Eldem, A., Ozcan, B.C., Kalmaz, S., and Ucuncu, M. (2025). A Sensitive and Reversible Fluorescent Probe for Selective Detection of Hg2\u207a and Au3\u207a Ions. J. Fluoresc., in print.","DOI":"10.1007\/s10895-025-04482-w"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"133934","DOI":"10.1016\/j.tet.2024.133934","article-title":"Ratiometic fluorescent detection of Au(III) and fluorescent \u201cturn-off\u201d identification of Cu(II)\/Hg(II) with a coumarin-based probe","volume":"155","author":"Xu","year":"2024","journal-title":"Tetrahedron"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Subasi, N.T. (2025). Colorimetric sensing of Au3+ ions in aqueous media: A xanthene-based probe for rapid and visual detection. Sens. Bio-Sens. Res., 48.","DOI":"10.1016\/j.sbsr.2025.100799"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"143936","DOI":"10.1016\/j.molstruc.2025.143936","article-title":"Viscosity-sensitive fluorescent probe based on diphenylamino-substituted triazaborolopyridinium","volume":"1349","author":"Rattanopas","year":"2026","journal-title":"J. Mol. Struct."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"111013","DOI":"10.1016\/j.dyepig.2022.111013","article-title":"Boronic acid derived salicylidenehydrazinylpyridine (BOSPY) complexes with aggregation-induced emission for fluorescence imaging of cellular organelles","volume":"210","author":"Wang","year":"2023","journal-title":"Dyes Pigments"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3349","DOI":"10.1007\/s11164-018-3311-6","article-title":"Synthesis, antileishmanial and cytotoxicity activities of fused and nonfused tetrahydroquinoline derivatives","volume":"44","author":"Madkour","year":"2018","journal-title":"Res. Chem. Intermed."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"E12","DOI":"10.1002\/jhet.1020","article-title":"Synthesis and antitumor evaluation of some new fused and binary pyridines","volume":"50","author":"Waly","year":"2013","journal-title":"J. Heterocycl. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"17","DOI":"10.21608\/ejchem.2010.1202","article-title":"Focus on the synthesis and reactions of some new pyridine carbonitrile derivatives as antimicrobial and antioxidant agents","volume":"53","author":"Sayed","year":"2010","journal-title":"Egypt J. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1002\/jhet.4175","article-title":"Synthesis of 3-cyano-2-pyridone derivative and its utility in the synthesis of some heterocyclic compounds with expecting antimicrobial activity","volume":"58","author":"Shaban","year":"2021","journal-title":"J. Heterocycl. Chem."},{"key":"ref_38","first-page":"178","article-title":"Synthesis and reaction of cyanopyridone derivatives and their potential biological activities","volume":"54","author":"Salman","year":"1999","journal-title":"Pharmazie"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"100782","DOI":"10.1016\/j.rechem.2023.100782","article-title":"A review of synthetic methods of 1,2,4-triazolopyridines and their therapeutic properties","volume":"5","author":"Mahmoodi","year":"2023","journal-title":"Results Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1134\/S1070428024080013","article-title":"Organic chemistry in russian Universities. achievements of recent Years","volume":"60","author":"Stoikov","year":"2024","journal-title":"Russ. J. Org. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"105181","DOI":"10.1016\/j.arabjc.2023.105181","article-title":"Triazolopyridine, a leitmotif of synthetic methods and pharmacological attributes: An extensive review","volume":"16","author":"Mohite","year":"2023","journal-title":"Arab. J. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.2174\/1385272821666170410145554","article-title":"Recent advances of 1,2,4-triazolo[3,4-a]pyridines: Synthesis and Bioactivities","volume":"21","author":"Shen","year":"2017","journal-title":"Curr. Org. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0065-2725(02)83003-3","article-title":"The chemistry of the triazolopyridines: An update","volume":"83","author":"Jones","year":"2002","journal-title":"Adv. Heterocycl. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/S0065-2725(08)60821-1","article-title":"The chemistry of the Triazolopyridines","volume":"34","author":"Jones","year":"1983","journal-title":"Adv. Heterocycl. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Abdel-Aziem, A., and Fouad, S.A. (2025). Recent advances in pyrazolo[3,4-b]pyridine chemistry: Synthesis techniques and biological activity. Mol. Divers., in print.","DOI":"10.1007\/s11030-025-11231-5"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1111\/cbdd.14098","article-title":"Pyrazolopyridine: An efficient pharmacophore in recent drug design and development","volume":"100","author":"Atukuri","year":"2022","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1007\/s11172-022-3487-1","article-title":"Methods for the synthesis of 1H-pyrazolo[3,4-b]pyridine derivatives","volume":"71","author":"Smolobochkin","year":"2022","journal-title":"Russ. Chem. Bull."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2861","DOI":"10.1080\/00397911.2020.1786126","article-title":"Advances in 4,6-dimethyl-3-amino-3H-pyrazolo[3,4-b] pyridine-based and their annulated systems","volume":"50","author":"Zoorob","year":"2020","journal-title":"Synth. Commun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2775","DOI":"10.3390\/molecules27092775","article-title":"1H-Pyrazolo[3,4-b]quinolines: Synthesis and properties over 100 years of Research","volume":"27","author":"Danel","year":"2022","journal-title":"Molecules"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"RCR5125","DOI":"10.59761\/RCR5125","article-title":"The chemistry of heterocycles in the 21st century","volume":"93","author":"Charushin","year":"2024","journal-title":"Russ. Chem. Rev."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2","DOI":"10.2174\/1570178616666190411102031","article-title":"Recent development in the chemistry of bicyclic 6+5 Systems, part I: Chemistry of Pyrazolo[3,4-b]pyridines","volume":"17","author":"Gouda","year":"2019","journal-title":"Lett. Org. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1007\/s10593-020-02830-1","article-title":"Microwave-assisted synthesis of pyrazolo[3,4-b]pyridine derivatives (microreview)","volume":"56","author":"Dyadyuchenko","year":"2020","journal-title":"Chem. Heterocycl. Compd."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"RCR5099","DOI":"10.59761\/RCR5099","article-title":"Functional pyrazolylpyridine ligands in the design of metal complexes with tunable properties","volume":"92","author":"Titova","year":"2023","journal-title":"Russ. Chem. Rev."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1002\/jhet.986","article-title":"Synthesis of pyrazolo[3,4-b]pyridin-6-ones","volume":"49","author":"Komarova","year":"2012","journal-title":"J. Heterocycl. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1517\/13543776.2013.749861","article-title":"Pyrazolo[3,4-b]pyridine kinase inhibitors: A patent review (2008\u2013present)","volume":"23","author":"Wenglowsky","year":"2013","journal-title":"Expert. Opin. Ther. Pat."},{"key":"ref_56","first-page":"136","article-title":"1,2,4-Triazine Chemistry part III: Synthetic strategies to functionalized bridgehead nitrogen heteroannulated 1,2,4-triazine systems and their regiospecific and pharmacological properties","volume":"10","author":"Makki","year":"2013","journal-title":"Curr. Org. Synth."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Dotsenko, V.V., Kindop, V.K., Kindop, V.K., Daus, E.S., Yudaev, I.V., Daus, Y.V., Bespalov, A.V., Buryi, D.S., Lukina, D.Y., and Aksenov, N.A. (2025). Synthesis of new phenothiazine\/3-cyanoquinoline and phenothiazine\/3-aminothieno[2,3-b]pyridine(-quinoline) heterodimers. Int. J. Mol. Sci., 26.","DOI":"10.20944\/preprints202509.1685.v1"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2699","DOI":"10.1134\/S1070363225604417","article-title":"Synthesis of (pyrido[3\u2019,2\u2019:4,5]thieno[3,2-d]pyrimidin-2-ylthio)acetic acids esters by the reaction of N-(thieno[2,3-b]pyridin-3-yl)-\u03b1-chloroacetamides with potassium thiocyanate","volume":"95","author":"Rudenko","year":"2025","journal-title":"Russ. J. Gen. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"134889","DOI":"10.1016\/j.tet.2025.134889","article-title":"Synthesis and structural characterization of 2-iminothiazoline\/quinoline and 2-iminothiazoline\/thieno[2,3-b]quinoline molecular hybrids with herbicide safening properties","volume":"186","author":"Kindop","year":"2025","journal-title":"Tetrahedron"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"609","DOI":"10.3390\/molecules28020609","article-title":"Alkyl 4-Aryl-6-amino-7-phenyl-3-(phenylimino)-4,7-dihydro- 3H-[1,2]dithiolo[3,4-b]pyridine-5-carboxylates: Synthesis and agrochemical Studies","volume":"28","author":"Dotsenko","year":"2023","journal-title":"Molecules"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Dotsenko, V.V., Jassim, N.T., Temerdashev, A.Z., Abdul-Hussein, Z.R., Aksenov, N.A., and Aksenova, I.V. (2023). New 6\u2032-Amino-5\u2032-cyano-2-oxo-1,2-dihydro-1\u2032H-spiro[indole-3,4\u2032-pyridine]-3\u2032-carboxamides: Synthesis, reactions, molecular docking studies and biological activity. Molecules, 28.","DOI":"10.3390\/molecules28073161"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1134\/S1070363220060043","article-title":"Reaction of 3-Amino-4,6-diarylthieno[2,3-b]pyridine-2-carboxamides with ninhydrin","volume":"90","author":"Dotsenko","year":"2020","journal-title":"Russ. J. Gen. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.1007\/s00706-019-02505-4","article-title":"Substituted N-(thieno[2,3-b]pyridine-3-yl)acetamides: Synthesis, reactions, and biological activity","volume":"150","author":"Dotsenko","year":"2019","journal-title":"Monatsh. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1134\/S1070363225601954","article-title":"Synthesis of 2,2-dimethyl-2,3-dihydropyrido[3\u2032,2\u2032: 4,5]thieno[3,2-d]pyrimidin-4(1H)-ones by reaction of 3-aminothieno[2,3-b]pyridine- 2-carboxamides with acetone","volume":"95","author":"Dotsenko","year":"2025","journal-title":"Russ. J. Gen. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1134\/S1070363223070046","article-title":"Mannich reaction involving 6-amino-4-methyl-2-(thio)oxo-1,2-dihydropyridine-3,5-dicarbonitriles","volume":"93","author":"Panaetov","year":"2023","journal-title":"Russ. J. Gen. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Temerdashev, A., Zorina, M., Feng, Y.Q., Gashimova, E., Dotsenko, V.V., Ioutsi, V., and Atapattu, S.N. (2024). Cyanoacetohydrazide as a novel derivatization agent for the determination of UHPLC-HRMS steroids in urine. Molecules, 29.","DOI":"10.3390\/molecules29112433"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"100162","DOI":"10.1016\/j.jcoa.2024.100162","article-title":"Phthalylglycyl chloride as a derivatization reagent for determination of urinary amino acids using ultra high-performance liquid chromatography coupled with high resolution mass spectrometry","volume":"6","author":"Temerdashev","year":"2024","journal-title":"J. Chromatogr. Open"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"124760","DOI":"10.1016\/j.jchromb.2025.124760","article-title":"A novel ionic liquid 3-(2-hydrazinyl-2-oxoethyl)-1-methyl-1H-imidazol-3-ium chloride as a derivatization reagent for HPLC-HRMS determination of steroid hormones in urine","volume":"1265","author":"Zorina","year":"2025","journal-title":"J. Chromatogr. B"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"100268","DOI":"10.1016\/j.jcoa.2025.100268","article-title":"Application of alrestatin chloride as a derivatizing reagent for the determination of amino acids, catecholamines and biogenic amines in urine","volume":"8","author":"Temerdashev","year":"2025","journal-title":"J. Chromatogr. Open"},{"key":"ref_70","first-page":"33","article-title":"Antidote and Growth-Regulating Activity of N1-Aryl-N2-(Substituted Nicotinonitrile) Hydrazones","volume":"N 7","author":"Dyadyuchenko","year":"2014","journal-title":"Agrochemistry"},{"key":"ref_71","first-page":"57","article-title":"A new growth regulator for rice plants","volume":"N 4","author":"Dyadyuchenko","year":"2021","journal-title":"Agrochemistry"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1134\/S1070363221100145","article-title":"Synthesis and biological Activity of new 3-Pyrazolyl-6-hydrazinylpyridazine Derivatives","volume":"91","author":"Gomktsyan","year":"2021","journal-title":"Russ. J. Gen. Chem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2401","DOI":"10.1134\/S107036321710022X","article-title":"A series of pyridines and pyridine based sulfa-drugs as antimicrobial agents: Design, synthesis and antimicrobial activity","volume":"87","author":"Moustafa","year":"2017","journal-title":"Russ. J. Gen. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1007\/BF00510110","article-title":"Some nucleophilic substitution reactions of 2-chloro-3-cyanopyridines","volume":"12","author":"Bomika","year":"1976","journal-title":"Chem. Heterocycl. Compd."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Radwan, M.A.A., Alshubramy, M.A., Abdel-Motaal, M., Hemdan, B.A., and El-Kady, D.S. (2020). Synthesis, molecular docking and antimicrobial activity of new fused pyrimidine and pyridine derivatives. Bioorg. Chem., 96.","DOI":"10.1016\/j.bioorg.2019.103516"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1080\/14756366.2022.2135512","article-title":"Biological evaluation, docking studies, and in silico ADME prediction of some pyrimidine and pyridine derivatives as potential EGFRWT and EGFRT790M inhibitors","volume":"38","author":"Elmaaty","year":"2023","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"ref_77","first-page":"861","article-title":"New pyridine and triazolopyridine derivatives: Synthesis, antimicrobial and antioxidant evaluation","volume":"74","author":"Kotb","year":"2017","journal-title":"Acta Pol. Pharm. Drug Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.3987\/COM-95-7037","article-title":"Cyclization of 2-dicyanomethylene-1,2-dihydro-pyridine-3-carbonitriles with hydrogen halides: A re-examination on the regioselectivity","volume":"41","author":"Victory","year":"1995","journal-title":"Heterocycles"},{"key":"ref_79","first-page":"667","article-title":"A concise synthesis and antimicrobial activity of a novel series of naphthylpyridine-3-carbonitrile compounds","volume":"70","author":"Kotb","year":"2013","journal-title":"Acta Pol. Pharm."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1134\/S1070363225601127","article-title":"Synthesis and spectral\u2013luminescent properties of 2-amino-6-chloro-4-(4-(dimethylamino)phenyl)pyridine-3,5-dicarbonitrile and compounds based on it","volume":"95","author":"Bardasov","year":"2025","journal-title":"Russ. J. Gen. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1007\/BF02251662","article-title":"Investigations on furopyridines. 10. Synthesis of 4-N-substituted 1H-furo[3,4]pyridin-3-ones","volume":"35","author":"Arustamova","year":"1999","journal-title":"Chem. Heterocycl. Compd."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1007\/BF00515429","article-title":"Azaindole derivatives. 67. Synthesis of N-substituted 1-benzyl-4-methyl-5-cyano-6-amino-7-azaindoles","volume":"22","author":"Sycheva","year":"1986","journal-title":"Chem. Heterocycl. Compd."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Flefel, E.M., Abbas, H.A.S., Abdel Mageid, R.E., and Zaghary, W.A. (2016). Synthesis and cytotoxic effect of some novel 1,2-dihydropyridin-3-carbonitrile and nicotinonitrile derivatives. Molecules, 21.","DOI":"10.3390\/molecules21010030"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"El-Sayed, A.A., Amr, A.E.G.E.E., EL-Ziaty, A.K., and Elsayed, E.A. (2019). Cytotoxic effects of newly synthesized heterocyclic candidates containing nicotinonitrile and pyrazole moieties on hepatocellular and cervical carcinomas. Molecules, 24.","DOI":"10.3390\/molecules24101965"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Aboukhatwa, S.M., Ibrahim, A.O., Aoyama, H., Al-Behery, A.S., Shaldam, M.A., El-Ashmawy, G., and Tawfik, H.O. (2022). Nicotinonitrile-derived apoptotic inducers: Design, synthesis, X-ray crystal structure and pim kinase inhibition. Bioorg. Chem., 129.","DOI":"10.1016\/j.bioorg.2022.106126"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1007\/s11164-016-2633-5","article-title":"Synthesis and anticancer activity of novel 2-substituted pyranopyridine derivatives","volume":"43","author":"Mohamed","year":"2017","journal-title":"Res. Chem. Intermed."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1016\/j.bmcl.2006.12.086","article-title":"Identification and structure\u2013activity relationships of substituted pyridones as inhibitors of Pim-1 kinase","volume":"17","author":"Cheney","year":"2007","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1002\/jhet.1990","article-title":"The use of Pinner type reaction for the synthesis of new indeno[2,1-c]pyridine-4-carbonitrile derivatives","volume":"52","author":"Nikam","year":"2015","journal-title":"J. Heterocycl. Chem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1002\/ardp.201300183","article-title":"Synthesis, Antibacterial, and antiviral Evaluation of new Heterocycles containing the pyridine Moiety","volume":"346","author":"Salem","year":"2013","journal-title":"Arch. Pharm."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1002\/jhet.3764","article-title":"Synthesis and in vitro evaluation of novel tetralin-pyrazolo[3,4-b]pyridine hybrids as potential anticancer agents","volume":"57","author":"Hamza","year":"2020","journal-title":"J. Heterocycl. Chem."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"10902","DOI":"10.3390\/molecules170910902","article-title":"Synthesis of a new series of pyridine and fused pyridine derivatives","volume":"17","year":"2012","journal-title":"Molecules"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"133261","DOI":"10.1016\/j.molstruc.2022.133261","article-title":"Functionalization of novel anti-microbial drug based on molecular docking study for nicotinonitrile analogs prepared by microwave irradiation","volume":"1264","author":"Alsafi","year":"2022","journal-title":"J. Mol. Struct."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Elewa, S.I., Abdel-Haleem, D.R., Tantawy, A.H., Mohamed, H.I., and Lashin, W.H. (2025). Exploring the larvicidal and pupicidal activities of new functionalized pyridines against Culex pipiens L. referring to molecular docking and SAR studies. Bioorg. Chem., 157.","DOI":"10.1016\/j.bioorg.2025.108283"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"3384","DOI":"10.1002\/jhet.4058","article-title":"Design and synthesis of new series of 3-cyanopyridine and pyrazolopyridine derivatives","volume":"57","author":"Keshk","year":"2020","journal-title":"J. Heterocycl. Chem."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.1002\/jhet.4533","article-title":"Efficient synthesis and biological evaluation of some new series of pyridine derivatives: Promising and potent new class of anticancer agents","volume":"59","author":"Abbas","year":"2022","journal-title":"J. Heterocycl. Chem."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1002\/jhet.966","article-title":"Synthesis and Anti-avian Influenza virus (H5N1) evaluation of some novel nicotinonitriles and their N-acylic nucleosides","volume":"49","author":"Rashad","year":"2012","journal-title":"J. Heterocycl. Chem."},{"key":"ref_97","first-page":"896","article-title":"Synthesis of new pyridoquinoxalines, thienopyridoquinoxalines and pyrimidothienopyridoquinoxalines","volume":"55","author":"Moustafa","year":"2000","journal-title":"Pharmazie"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1847","DOI":"10.1080\/00397911.2018.1468911","article-title":"Facile synthesis and characterization of novel pyrido[3\u2032,2\u2032:4,5]thieno[3,2-d]pyrimidin-4(3H)-one and pyrido[2\u2032,3\u2032:3,4]pyrazolo[1,5-a]pyrimidine incorporating 1,3-diarylpyrazole moiety","volume":"48","author":"Sanad","year":"2018","journal-title":"Synth. Commun."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1007\/s10593-010-0507-0","article-title":"A convenient route for the synthesis of some new bi- and triheterocondensed uracils","volume":"46","year":"2010","journal-title":"Chem. Heterocycl. Compd."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1080\/17415993.2011.593635","article-title":"Synthesis and antimicrobial evaluation of some new thienopyridine, pyrazolopyridine and pyridothienopyrimidine derivatives","volume":"32","author":"Rateb","year":"2011","journal-title":"J. Sulfur. Chem."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"8648","DOI":"10.1016\/j.tet.2014.09.047","article-title":"New heterocyclic systems derived from pyridine: New substrates for the investigation of the azide\/tetrazole equilibrium","volume":"70","author":"Sirakanyan","year":"2014","journal-title":"Tetrahedron"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1007\/s10593-012-1017-z","article-title":"New heterocyclic systems based on 1-hydrazinyl-5,6,7,8- tetrahydro[2,7]naphthyridine: 7,8,9,10-tetrahydro[1,2,4]triazolo[3,4-a]- and 7,8,9,10-tetrahydro[1,2,4]triazolo[5,1-a][2,7]- naphthyridines","volume":"48","author":"Sirakanyan","year":"2012","journal-title":"Chem. Heterocycl. Compd."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2215","DOI":"10.1021\/acs.jmedchem.6b01576","article-title":"Discovery of first-in-class, potent, and orally bioavailable embryonic ectoderm development (EED) inhibitor with robust anticancer efficacy","volume":"60","author":"Huang","year":"2017","journal-title":"J. Med. Chem."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1007\/BF00529375","article-title":"Synthesis and structure of 6-hydrazinyl-2,4,5-trichloronicotinonitrile","volume":"28","author":"Kvartsev","year":"1992","journal-title":"Chem. Heterocycl. Compd."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2000377","DOI":"10.1002\/ardp.202000377","article-title":"Synthesis and anticancer properties of novel hydrazone derivatives incorporating pyridine and isatin moieties","volume":"354","author":"Zebbiche","year":"2021","journal-title":"Arch. Pharm."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1248\/cpb.13.113","article-title":"Janovsky reaction of Nitropyridines. II. Preparation of 5-nitronicotinic acid and its related compounds","volume":"13","author":"Nakadate","year":"1965","journal-title":"Chem. Pharm. Bull."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1021\/jm00331a005","article-title":"Vitamin B6 Analogs. II.1,2 synthesis of 4,6-dimethyl-5-mercapto-3-pyridinemethanol and of 5-mercapto-6-methyl-3,4-pyridinedimethanol hydrochlorides","volume":"7","author":"Greene","year":"1964","journal-title":"J. Med. Chem."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1002\/jhet.5570020216","article-title":"Pyrazolo[3,4-b]pyridines and pyrazolo[3\u2032,4\u2032:6,5]pyrido[2,3-d]pyrimidines","volume":"2","author":"Cottis","year":"1965","journal-title":"J. Heterocycl. Chem."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.molstruc.2011.06.033","article-title":"Synthesis, X-ray and spectroscopic analysis of 2-hydrazinyl-6-methyl-4-(methoxymethyl)-5-nitropyridine-3-carbonitrile","volume":"1001","author":"Halambek","year":"2011","journal-title":"J. Mol. Struct."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1134\/S1070428018060088","article-title":"Synthesis of 2-Hydrazinylpyridine-3,4-dicarbonitriles and their Reaction with salicylaldehyde Derivatives","volume":"54","author":"Ershov","year":"2018","journal-title":"Russ. J. Org. Chem."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"4461","DOI":"10.1016\/S0040-4020(01)87286-0","article-title":"Acces aux alkyl (ou aryl)-4 diamino-3,6 pyrazolo[3,4-b]pyridines substituees en 5 par un groupe SR ou Cl","volume":"42","author":"Pochat","year":"1986","journal-title":"Tetrahedron"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2241","DOI":"10.1246\/bcsj.65.2241","article-title":"Studies on fused 2(1H)-pyridenethiones: New routes for the synthesis of fused 1H-pyrazolo[3,4-b]pyridines and fused thieno[2,3-b]pyridines","volume":"65","author":"Elgemeie","year":"1992","journal-title":"Bull. Chem. Soc. Jpn."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1023\/A:1010438307254","article-title":"Synthesis and anticonvulsant activity of pyrazolo[3,4-b]pyrano(thiopyrano)[4,3-d]pyridine and pyrazolo[3,4-c]isoquinoline derivatives","volume":"35","author":"Paronikyan","year":"2001","journal-title":"Pharm. Chem. J."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1023\/A:1023979230025","article-title":"Synthesis ad some conversions of partially hydrogenated 1-aminopyrano(thiopyrano)[4,3-d]pyrazolo[3,4-b]pyridines and pyrazolo[3,4-c]isoquinolines","volume":"39","author":"Paronikyan","year":"2003","journal-title":"Chem. Heterocycl. Compd."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1134\/S1070428022070089","article-title":"Synthesis and optical Properties of 3,4-diamino-6-aryl-1H-pyrazolo[3,4-b]pyridine-5-carbonitriles","volume":"58","author":"Alekseeva","year":"2022","journal-title":"Russ. J. Org. Chem."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1134\/S1070363222090109","article-title":"Synthesis of new fused derivatives of 4-(fur-2-yl)pyrano[4,3-b]pyridines","volume":"92","author":"Dabaeva","year":"2022","journal-title":"Russ. J. Gen. Chem."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1134\/S1070428020050176","article-title":"Synthesis of novel 1-pyrazolyl-2,7-naphthyridine derivatives","volume":"56","author":"Sirakanyan","year":"2020","journal-title":"Russ. J. Org. Chem."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"11419","DOI":"10.1021\/acs.jmedchem.5c00375","article-title":"Design, synthesis, and evaluation of pyrazolopyridine derivatives as novel calreticulin (CALR) ligands that inhibit triple-negative breast cancer (TNBC) via inducing calcium overloading","volume":"68","author":"Lu","year":"2025","journal-title":"J. Med. Chem."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"8770","DOI":"10.1021\/jm3010724","article-title":"Discovery of 3-cyclopropylmethyl-7-(4-phenylpiperidin-1-yl)-8-trifluoromethyl [1,2,4]triazolo[4,3-a]pyridine (JNJ-42153605): A positive allosteric modulator of the metabotropic glutamate 2 receptor","volume":"55","author":"Cid","year":"2012","journal-title":"J. Med. Chem."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"8685","DOI":"10.1021\/jm300912k","article-title":"Synthesis, Evaluation, and radiolabeling of new potent positive allosteric modulators of the metabotropic glutamate receptor 2 as potential tracers for positron emission tomography imaging","volume":"55","author":"Cid","year":"2012","journal-title":"J. Med. Chem."},{"key":"ref_121","first-page":"548","article-title":"Cyclization reactions of nitriles. V. 2-Aryl-3-(2-thenoyl)-1,1-dicyanopropanes and pyridine derivatives based on them","volume":"18","author":"Sharanin","year":"1982","journal-title":"J. Org. Chem. USSR"},{"key":"ref_122","first-page":"1382","article-title":"Cyclization of nitriles. IX. Syntheses based on 2-aryl-3-aroyl-1,1-dicyanopropanes","volume":"20","author":"Shestopalov","year":"1984","journal-title":"J. Org. Chem. USSR"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1002\/recl.19941130105","article-title":"New pyridinecarbonitriles from fluoro arylpropenones","volume":"113","author":"Mishriky","year":"1994","journal-title":"Recl. Trav. Chim. Pays-Bas"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"5375","DOI":"10.1016\/S0040-4039(00)92390-6","article-title":"The reaction of malononitrile with chalcone: A controversial chemical process","volume":"32","author":"Victory","year":"1991","journal-title":"Tetrahedron Lett."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Igushkina, A.V., Golovanov, A.A., Boyarskaya, I.A., Kolesnikov, I.E., and Vasilyev, A.V. (2020). Stereoselective synthesis of multisubstituted cyclohexanes by reaction of conjugated enynones with malononitrile in the presence of LDA. Molecules, 25.","DOI":"10.3390\/molecules25245920"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1055\/s-1990-27123","article-title":"Michael-addition of malononitrile to 1,3-diaryl-2-propen-1-ones","volume":"1990","author":"Tabba","year":"1990","journal-title":"Synthesis"},{"key":"ref_127","first-page":"567","article-title":"New aspects of Michael reaction: Reaction of 1,3-diarylpropenones with active cyano compounds","volume":"30","author":"Sharaf","year":"1991","journal-title":"Ind. J. Chem. Sect. B"},{"key":"ref_128","first-page":"373","article-title":"Reactions of vinylketones and \u03b2-chloroketones with malononitrile: A novel synthesis of cyclohexanol derivatives","volume":"44","author":"Darwish","year":"2001","journal-title":"Egypt. J. Chem."},{"key":"ref_129","first-page":"135","article-title":"A rapid one-pot synthesis of 2,4,6-triaryl-3-aroyl-4-hydroxy-1,1-cyclohexane- dicarbonitriles and 2-aminoisophthalo nitriles under microwave activation","volume":"42","author":"Laskar","year":"2003","journal-title":"Ind. J. Chem. Sect. B"},{"key":"ref_130","first-page":"205","article-title":"Synthesis of trifluoromethyl-containing carbo- and heterocycles based on reactions of \u03b1,\u03b2-unsaturated ketones with malonodinitrile and cyanoacetamides","volume":"33","author":"Sanin","year":"1997","journal-title":"Russ. J. Nondestruct. Test."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1007\/s00706-004-0265-8","article-title":"Reactions of heteroaryl substituted propenones","volume":"136","author":"Sprang","year":"2005","journal-title":"Monatsh. Chem."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"o1766","DOI":"10.1107\/S1600536806012086","article-title":"3-Benzoyl-4-hydroxy-2,4,6-triphenylcyclohexane-1,1-dicarbonitrile","volume":"62","author":"Rong","year":"2006","journal-title":"Acta Crystallogr. E"},{"key":"ref_133","first-page":"1977","article-title":"A clean and efficient method for the synthesis of 3-aroyl-2,4,6-triaryl-4-hydroxy-1,1-cyclohexanedicarbonitriles in water","volume":"22","author":"Wang","year":"2010","journal-title":"Asian J. Chem."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"147","DOI":"10.3184\/174751911X12977065405044","article-title":"Synthesis of a series of highly substituted cyclohexanols via Michael addition in an aqueous medium","volume":"35","author":"Lu","year":"2011","journal-title":"J. Chem. Res."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1134\/S1070428011080227","article-title":"Synthesis of 2,6-diaryl-3-benzoyl-4-hydroxy-4-phenyl- 1,1-cyclohexanedinitriles","volume":"47","author":"Gein","year":"2011","journal-title":"Russ. J. Org. Chem."},{"key":"ref_136","first-page":"1064","article-title":"Synthesis of 1,3,5-triaryl-2-aroylcyclohexanol derivatives and crystal structure under solvent-free conditions","volume":"31","author":"Diao","year":"2011","journal-title":"Chin. J. Org. Chem."},{"key":"ref_137","first-page":"3678","article-title":"Quinine catalysed asymmetric Michael additions in a sustainable solvent","volume":"5","author":"Comerford","year":"2014","journal-title":"RSC Adv."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"4516","DOI":"10.1016\/j.tet.2019.06.041","article-title":"Multicomponent reaction of conjugated enynones with malononitrile and sodium alkoxides: Complex reaction mechanism of the formation of pyridine derivatives","volume":"75","author":"Kuznetcova","year":"2019","journal-title":"Tetrahedron"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"13205","DOI":"10.1021\/acs.joc.3c01435","article-title":"Enantioselective Michael addition of malononitrile to unsaturated ketones catalyzed by rare-earth metal amides RE[N(SiMe3)2]3 with phenoxy-functionalized TsDPEN ligands","volume":"88","author":"Ren","year":"2023","journal-title":"J. Org. Chem."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"5349","DOI":"10.1021\/acs.joc.4c02444","article-title":"Unanticipated three-component cascade and sequential cyclization: Highly diastereoselective synthesis of polyfunctionalized cyclohexanes","volume":"90","author":"He","year":"2025","journal-title":"J. Org. Chem."},{"key":"ref_141","unstructured":"Benko, Z.L., Crouse, G.D., Erickson, W.R., Gifford, J.M., Gustafson, G.D., Orr, N., and Watson, G.B. (2009). Pesticidal Compositions. (U.S. Patent 20090093500)."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1002\/ps.1829","article-title":"The unique role of halogen substituents in the design of modern agrochemicals","volume":"66","author":"Jeschke","year":"2010","journal-title":"Pest. Manag. Sci."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1002\/ps.4540","article-title":"Latest generation of halogen-containing pesticides","volume":"73","author":"Jeschke","year":"2017","journal-title":"Pest. Manag. Sci."},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Jeschke, P., Kr\u00e4mer, W., Schirmer, U., and Witschel, M. (2012). The unique role of halogen substituents in the design of modern crop protection compounds (Chapter 4). Modern Methods in Crop Protection Research, Wiley.","DOI":"10.1002\/9783527655908"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"e202101513","DOI":"10.1002\/ejoc.202101513","article-title":"Manufacturing approaches of new Halogenated Agrochemicals","volume":"2022","author":"Jeschke","year":"2022","journal-title":"Eur. J. Org. Chem."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1002\/(SICI)1521-3897(199907)341:5<417::AID-PRAC417>3.0.CO;2-A","article-title":"Influence of chlorine substituents on biological activity of chemicals","volume":"341","author":"Naumann","year":"1999","journal-title":"J. Prakt. Chem."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.plantsci.2018.02.014","article-title":"Review on the significance of chlorine for crop yield and quality","volume":"270","author":"Geilfus","year":"2018","journal-title":"Plant Sci."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"e202401042","DOI":"10.1002\/cssc.202401042","article-title":"New active ingredients for sustainable modern chemical crop protection in agriculture","volume":"18","author":"Jeschke","year":"2025","journal-title":"ChemSusChem"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"233","DOI":"10.3390\/reactions3020018","article-title":"Recent progresses in the preparation of chlorinated molecules: Electrocatalysis and photoredox catalysis in the spotlight","volume":"3","author":"Parisotto","year":"2022","journal-title":"Reactions"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1007\/s10593-020-02843-w","article-title":"Good pyridine hunting: A biomimic compound, a modifier and a unique pharmacophore in agrochemicals","volume":"56","author":"Zakharychev","year":"2020","journal-title":"Chem. Heterocycl. Compd."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.bmc.2015.09.031","article-title":"Discovery of pyridine-based agrochemicals by using intermediate derivatization methods","volume":"24","author":"Guan","year":"2016","journal-title":"Bioorg. Med. Chem."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.aac.2024.10.002","article-title":"Development of novel pyridine-based agrochemicals: A review","volume":"4","author":"Zakharychev","year":"2025","journal-title":"Adv. Agrochem."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1614\/WT-D-15-00131.1","article-title":"2,4-D past, present, and future: A review","volume":"30","author":"Peterson","year":"2016","journal-title":"Weed Technol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"145","DOI":"10.32931\/io1921r","article-title":"Antidotes for reduction of phytotoxicity of the residues of sulfonylurea herbicides","volume":"2","author":"Chkanikov","year":"2019","journal-title":"INEOS OPEN"},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Deng, X. (2022). Current advances in the action mechanisms of safeners. Agronomy, 12.","DOI":"10.3390\/agronomy12112824"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"5499","DOI":"10.1021\/acs.jafc.2c01565","article-title":"Research progress in the design and synthesis of herbicide safeners: A review","volume":"70","author":"Jia","year":"2022","journal-title":"J. Agric. Food Chem."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"11320","DOI":"10.1021\/acs.jafc.3c03585","article-title":"Review on the discovery of novel natural herbicide safeners","volume":"71","author":"Leng","year":"2023","journal-title":"J. Agric. Food Chem."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"2451","DOI":"10.1021\/acs.jafc.3c08923","article-title":"Herbicide safeners: From molecular structure design to safener activity","volume":"72","author":"Zhao","year":"2024","journal-title":"J. Agric. Food Chem."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1134\/S1070363222090080","article-title":"Oxidation of 2-cyanothioacrylamides with sodium nitrite in acidic medium","volume":"92","author":"Dahno","year":"2022","journal-title":"Russ. J. Gen. Chem."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1007\/s13738-022-02688-4","article-title":"Bromine- and iodine-mediated oxidative dimerization of cyanothioacetamide derivatives: Synthesis of new functionalized 1,2,4-thiadiazoles","volume":"20","author":"Krivokolysko","year":"2023","journal-title":"J. Iran. Chem. Soc."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1134\/S1070363223060063","article-title":"7-(2-Aryl-1-cyanovinyl)-1,2,3,4-tetrahydropyrazolo[1,5-a][1,3,5]triazine-8-carbonitriles: Synthesis and biological Activity","volume":"93","author":"Stepanova","year":"2023","journal-title":"Russ. J. Gen. Chem."},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Dotsenko, V.V., Bespalov, A.V., Sinotsko, A.E., Temerdashev, A.Z., Vasilin, V.K., Varzieva, E.A., Strelkov, V.D., Aksenov, N.A., and Aksenova, I.V. (2024). 6-Amino-4-aryl-7-phenyl-3-(phenylimino)-4,7-dihydro-3H-[1,2]dithiolo[3,4-b]pyridine-5-carboxamides: Synthesis, biological activity, quantum chemical studies and in silico docking studies. Int. J. Mol. Sci., 25.","DOI":"10.20944\/preprints202312.0487.v1"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.jfluchem.2008.10.005","article-title":"Synthesis of 3-cyano-2-fluoropyridines","volume":"130","author":"Shestopalov","year":"2009","journal-title":"J. Fluor. Chem."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"6070","DOI":"10.1021\/acs.jmedchem.1c01941","article-title":"Overcoming paradoxical Kinase priming by a novel MNK1 Inhibitor","volume":"65","author":"Alarcon","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1107\/S0021889808042726","article-title":"OLEX2: A Complete Structure Solution, Refinement and Analysis Program","volume":"42","author":"Dolomanov","year":"2009","journal-title":"J. Appl. Crystallogr."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1107\/S0108767307043930","article-title":"A Short History of SHELX","volume":"64","author":"Sheldrick","year":"2008","journal-title":"Acta Crystallogr. Sect. A"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1107\/S2053229614024218","article-title":"Crystal structure refinement with SHELXL","volume":"71","author":"Sheldrick","year":"2015","journal-title":"Acta Crystallogr. Sect. 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