Applications of the Ritter reaction in the synthesis of biologically active compounds: A review

Reshma Bhanudas Shevale; Smita Ravindra Waghmare

doi:10.5155/eurjchem.17.3.289-318.2811

PDF

Published: Sep 30, 2026

DOI: https://doi.org/10.5155/eurjchem.17.3.289-318.2811

Keywords:

Nitriles, Alcohol, Amines, Amides, Inhibitors, Ritter reaction

Section

Review Article

Issue

Vol. 17 No. 3 (2026): September 2026

Dates

Received 2026-06-13
Accepted 2026-07-30
Published 2026-09-30

Reshma Bhanudas Shevale

Modern Education Society's Nowrosjee Wadia College, Pune-1 Affiliated to Savitribai Phule Pune University, Pune, Maharashtra 411001, India

https://orcid.org/0009-0002-0625-3853

Smita Ravindra Waghmare

Modern Education Society's Nowrosjee Wadia College, Pune-1 Affiliated to Savitribai Phule Pune University, Pune, Maharashtra 411001, India

https://orcid.org/0000-0002-6957-0189

Abstract

Nitrogen-containing compounds play a fundamental role in biological systems. Proteins, the essential macromolecules responsible for virtually all cellular functions, are composed of amino acids linked through amide (peptide) bonds, highlighting the critical importance of nitrogen-containing functionalities in life processes. Ritter reaction methodologies have provided access to novel amide-containing scaffolds, which are valuable in medicinal chemistry and the creation of drug libraries. Ritter reactions are widely used in the synthesis of highly functionalized heterocycles, fused heterocycles and linear amides. These classes of compounds exhibit notable biological activities, including antibacterial, antiviral, antiproliferative, and anticancer activities. This review aims to compile recent advancements and applications of the Ritter reaction and mainly focuses on synthetic strategies for the synthesis of different classes of bioactive compounds. The evaluation of potential therapeutic applications of the most promising molecules synthesized using Ritter reaction is also covered in the present review.

This Abstract was viewed 108 times |

Article PDF downloaded 22 times

How to Cite

(1)

Shevale, R. B.; Waghmare, S. R. Applications of the Ritter Reaction in the Synthesis of Biologically Active Compounds: A Review. Eur. J. Chem. 2026, 17, 289-318.

Links for Article

Crossref - Scopus - Google - European PMC

References

[1]. Pedrood, K.; Bahadorikhalili, S.; Lotfi, V.; Larijani, B.; Mahdavi, M. Catalytic and non-catalytic amidation of carboxylic acid substrates. Mol Divers 2021, 26 (2), 1311-1344.
https://doi.org/10.1007/s11030-021-10252-0

[2]. Chen, M.; Chen, X.; Hu, Y.; Ye, R.; Lv, J.; Li, B.; Zhang, F. Recent advances of Ritter reaction and its synthetic applications. Org. Chem. Front. 2021, 8 (16), 4623-4664.
https://doi.org/10.1039/D1QO00496D

[3]. Ritter, J. J.; Kalish, J. A New Reaction of Nitriles. II. Synthesis of t-Carbinamines. J. Am. Chem. Soc. 1948, 70 (12), 4048-4050.
https://doi.org/10.1021/ja01192a023

[4]. Ritter, J. J.; Minieri, P. P. A New Reaction of Nitriles. I. Amides from Alkenes and Mononitriles1. J. Am. Chem. Soc. 1948, 70 (12), 4045-4048.
https://doi.org/10.1021/ja01192a022

[5]. Hughes, D. L.; Smith, G. B.; Liu, J.; Dezeny, G. C.; Senanayake, C. H.; Larsen, R. D.; Verhoeven, T. R.; Reider, P. J. Mechanistic Study of the Jacobsen Asymmetric Epoxidation of Indene. J. Org. Chem. 1997, 62 (7), 2222-2229.
https://doi.org/10.1021/jo961735i

[6]. Stevens, R. V.; Kenney, P. M. Studies on the stereochemistry of nucleophilic additions to tetrahydropyridinium salts. Expeditious stereospecific total syntheses of (+)-makomakine, (+)-aristoteline, and (±)-hobartine. J. Chem, Soc, Chem, Commun, 1983, 384-386.
https://doi.org/10.1039/C39830000384

[7]. Phan Thi, P. D.; Dang, T. A.; Vu, B. D.; Phan, D. C. Simple and Economical Process for Producing Amantadine Hydrochloride. ACS Omega 2022, 7 (6), 4787-4790.
https://doi.org/10.1021/acsomega.1c04652

[8]. Liu, X.; Sun, Y.; Hong, S.; Ji, X.; Gao, W.; Yuan, H.; Zhang, Y.; Lei, B.; Tang, L.; Fan, Z. Synthesis of fungicidal morpholines and isochromenopyridinones via acid-catalyzed intramolecular reactions of isoindolinones. Org. Biomol. Chem. 2024, 22 (1), 120-125.
https://doi.org/10.1039/D3OB01717F

[9]. Rozhkova, Y. S.; Pegushina, A. S.; Morozov, V. V.; Eroshenko, D. V.; Shklyaev, Y. V. Acid-catalyzed domino reaction of 2-(2-methoxyphenyl)-substituted cycloalkanols with aromatic/heteroaromatic ortho-aminonitriles: Diastereoselective access to polycyclic acridines and related heterocycles. Tetrahedron Lett. 2026, 175, 155904.
https://doi.org/10.1016/j.tetlet.2025.155904

[10]. Jiang, Z.; Ye, J.; Jiang, L.; Zhao, Y. New approach to 3-oxo-4-aza-5α-androst-1-ene-17β-(--butylcarboxamide). Steroids 2005, 70 (10), 690-693.
https://doi.org/10.1016/j.steroids.2005.03.009

[11]. Rasmusson, G. H.; Reynolds, G. F.; Utne, T.; Jobson, R. B.; Primka, R. L.; Berman, C.; Brooks, J. R. Azasteroids as inhibitors of rat prostatic 5.alpha.-reductase. J. Med. Chem. 1984, 27 (12), 1690-1701.
https://doi.org/10.1021/jm00378a028

[12]. Rasmusson, G. H.; Reynolds, G. F.; Steinberg, N. G.; Walton, E.; Patel, G. F.; Liang, T.; Cascieri, M. A.; Cheung, A. H.; Brooks, J. R.; Berman, C. Azasteroids: structure-activity relationships for inhibition of 5.alpha.-reductase and of androgen receptor binding. J. Med. Chem. 1986, 29 (11), 2298-2315.
https://doi.org/10.1021/jm00161a028

[13]. Rasmusson, G. H.; Reynolds. G. F. Merck & Co. Inc., USA. Europe Patent 1985, 18, 85-155096. https://patentimages.storage.googleapis.com/01/f1/24/51111a65714731/EP0155096B1.pdf

[14]. Heinzl, S. Androgenetic alopecia: finasteride treated hair loss. Med. Monatsschr. Pharm. 1999, 22, 124-127.

[15]. Tosti, A.; Piraccini, B. M. Finasteride and the hair cycle. J. Am. Acad. Dermatol. 2000, 42 (5), 848-849.
https://doi.org/10.1067/mjd.2000.103272

[16]. Coltman, Jr., C. A.; Thompson, Jr., I. M.; Feigl, P. Prostate Cancer Prevention Trial (PCPT) Update. Eur. Urol. 1999, 35 (5-6), 544-547.
https://doi.org/10.1159/000019895

[17]. Brink, C. B.; Harvey, B. H.; Bodenstein, J.; Venter, D. P.; Oliver, D. W. Recent advances in drug action and therapeutics: Relevance of novel concepts in G‐protein‐coupled receptor and signal transduction pharmacology. Brit J. Clinical Pharma 2004, 57 (4), 373-387.
https://doi.org/10.1111/j.1365-2125.2003.02046.x

[18]. Hulshof, J. W.; Vischer, H. F.; Verheij, M. H.; Fratantoni, S. A.; Smit, M. J.; de Esch, I. J.; Leurs, R. Synthesis and pharmacological characterization of novel inverse agonists acting on the viral-encoded chemokine receptor US28. Bioorg. amp; Med. Chem. 2006, 14 (21), 7213-7230.
https://doi.org/10.1016/j.bmc.2006.06.054

[19]. Von Rybinski, W.; Hill, K. Novel Surfactants: Preparation Application, and Biodegradability; Marcel Dekker; New York; (Ed.: K. Holmberg), Marcel Dekker, New York, 1998, 31-85.

[20]. Hill, K.; Rybinski, W. v.; Stoll, G. Alkyl Polyglycosides: Technology, Properties, Applications; Hill, K.; etc.; Rybinski, W. von; Stoll, G., Eds.; Wiley-VCH Verlag: Weinheim, Germany, 1996.
https://doi.org/10.1002/9783527614691

[21]. Yamaguchi, T. New horizons in hydrogen bonded clusters in solution. Pure Appl. Chem. 1999, 71 (9), 1741-1751.
https://doi.org/10.1351/pac199971091741

[22]. Fabry, B. D. Surfactant mixtures and compositions containing these. DE:4400632:C1, March 23, 1995. https://patents.google.com/patent/DE4400632C1/en?oq=DE+4%2c400%2c632%2c

[23]. Fabry, B. D. Mouth and tooth care agent. DE:4406745:A1, September 7, 1995. https://patents.google.com/patent/DE4406745A1/en?oq=DE+4%2c406%2c745

[24]. Hildreth, J. E. N-d-Gluco-N-methylalkanamide compounds, a new class of non-ionic detergents for membrane biochemistry. Biochem. J. 1982, 207 (2), 363-366.
https://doi.org/10.1042/bj2070363

[25]. Sato, I.; Morihira, K.; Inami, H.; Kubota, H.; Morokata, T.; Suzuki, K.; Hamada, N.; Iura, Y.; Nitta, A.; Imaoka, T.; Takahashi, T.; Takeuchi, M.; Ohta, M.; Tsukamoto, S. Synthesis and structure-activity relationships of N-{1-[(6-fluoro-2-naphthyl)methyl]piperidin-4-yl}benzamide derivatives as novel CCR3 antagonists. Bioorg. amp; Med. Chem. 2008, 16 (1), 144-156.
https://doi.org/10.1016/j.bmc.2007.10.003

[26]. Bosse, T. D.; Larson, D. P.; Wagner, R.; Hutchinson, D. K.; Rockway, T. W.; Kati, W. M.; Liu, Y.; Masse, S.; Middleton, T.; Mo, H.; Montgomery, D.; Jiang, W.; Koev, G.; Kempf, D. J.; Molla, A. Synthesis and SAR of novel 1,1-dialkyl-2(1H)-naphthalenones as potent HCV polymerase inhibitors. Bioorg. Med. Chem. Lett. 2008, 18 (2), 568-570.
https://doi.org/10.1016/j.bmcl.2007.11.088

[27]. Wagner, R.; Larson, D. P.; Beno, D. W.; Bosse, T. D.; Darbyshire, J. F.; Gao, Y.; Gates, B. D.; He, W.; Henry, R. F.; Hernandez, L. E.; Hutchinson, D. K.; Jiang, W. W.; Kati, W. M.; Klein, L. L.; Koev, G.; Kohlbrenner, W.; Krueger, A. C.; Liu, J.; Liu, Y.; Long, M. A.; Maring, C. J.; Masse, S. V.; Middleton, T.; Montgomery, D. A.; Pratt, J. K.; Stuart, P.; Molla, A.; Kempf, D. J. Inhibitors of Hepatitis C Virus Polymerase: Synthesis and Biological Characterization of Unsymmetrical Dialkyl-Hydroxynaphthalenoyl-benzothiadiazines. J. Med. Chem. 2009, 52 (6), 1659-1669.
https://doi.org/10.1021/jm8010965

[28]. Randolph, J. T.; Flentge, C. A.; Huang, P. P.; Hutchinson, D. K.; Klein, L. L.; Lim, H. B.; Mondal, R.; Reisch, T.; Montgomery, D. A.; Jiang, W. W.; Masse, S. V.; Hernandez, L. E.; Henry, R. F.; Liu, Y.; Koev, G.; Kati, W. M.; Stewart, K. D.; Beno, D. W.; Molla, A.; Kempf, D. J. Synthesis and Biological Characterization of B-Ring Amino Analogues of Potent Benzothiadiazine Hepatitis C Virus Polymerase Inhibitors. J. Med. Chem. 2009, 52 (10), 3174-3183.
https://doi.org/10.1021/jm801485z

[29]. Lewis, A.; Shepherd, R. G. In Medical Chemistry; Burger, A., Ed.; Interscience Publishers: New York, 1970; Part I, Chapter 19. ISBN 10: 0471123455

[30]. Hoover, J. R. E.; Stedman, R. J. In Medical Chemistry; Burger, A., Ed.; Interscience Publishers: New York, 1970; Part I, Chapter 18. ISBN 10: 0471123455

[31]. Marks, P. A. Discovery and development of SAHA as an anticancer agent. Oncogene 2007, 26 (9), 1351-1356.
https://doi.org/10.1038/sj.onc.1210204

[32]. Marks, P. A.; Breslow, R. Dimethyl sulfoxide to vorinostat: development of this histone deacetylase inhibitor as an anticancer drug. Nat Biotechnol 2007, 25 (1), 84-90.
https://doi.org/10.1038/nbt1272

[33]. Bates, S. E.; Zhan, Z.; Steadman, K.; Obrzut, T.; Luchenko, V.; Frye, R.; Robey, R. W.; Turner, M.; Gardner, E. R.; Figg, W. D.; Steinberg, S. M.; Ling, A.; Fojo, T.; To, K. W.; Piekarz, R. L. Laboratory correlates for a phase II trial of romidepsin in cutaneous and peripheral T‐cell lymphoma. Br J. Haematol 2009, 148 (2), 256-267.
https://doi.org/10.1111/j.1365-2141.2009.07954.x

[34]. Varasi, M.; Thaler, F.; Abate, A.; Bigogno, C.; Boggio, R.; Carenzi, G.; Cataudella, T.; Dal Zuffo, R.; Fulco, M. C.; Rozio, M. G.; Mai, A.; Dondio, G.; Minucci, S.; Mercurio, C. Discovery, Synthesis, and Pharmacological Evaluation of Spiropiperidine Hydroxamic Acid Based Derivatives as Structurally Novel Histone Deacetylase (HDAC) Inhibitors. J. Med. Chem. 2011, 54 (8), 3051-3064.
https://doi.org/10.1021/jm200146u

[35]. Seeman, P.; Lee, T.; Chau-Wong, M.; Wong, K. Antipsychotic drug doses and neuroleptic/dopamine receptors. Nature 1976, 261 (5562), 717-719.
https://doi.org/10.1038/261717a0

[36]. Gould, R. J.; Murphy, K. M.; Reynolds, I. J.; Snyder, S. H. Antischizophrenic drugs of the diphenylbutylpiperidine type act as calcium channel antagonists. Proc. Natl. Acad. Sci. U.S.A. 1983, 80 (16), 5122-5125.
https://doi.org/10.1073/pnas.80.16.5122

[37]. Grantham, C.; Main, M.; Cannell, M. Fluspirilene block of N‐type calcium current in NGF‐differentiated PC 12 cells. British J. Pharmacology 1994, 111 (2), 483-488.
https://doi.org/10.1111/j.1476-5381.1994.tb14762.x

[38]. Sah, D. W.; Bean, B. P. Inhibition of P-type and N-type calcium channels by dopamine receptor antagonists.. Mol. Pharmacol. 1994, 45 (1), 84-92.
https://doi.org/10.1016/S0026-895X(25)09907-9

[39]. Enyeart, J. J.; Biagi, B. A.; Day, R. N.; Sheu, S. S.; Maurer, R. A. Blockade of low and high threshold Ca2+ channels by diphenylbutylpiperidine antipsychotics linked to inhibition of prolactin gene expression.. J. Biol. Chem. 1990, 265 (27), 16373-16379.
https://doi.org/10.1016/S0021-9258(17)46233-8

[40]. Galizzi, J. P.; Fosset, M.; Romey, G.; Laduron, P.; Lazdunski, M. Neuroleptics of the diphenylbutylpiperidine series are potent calcium channel inhibitors. Proc. Natl. Acad. Sci. U.S.A. 1986, 83 (19), 7513-7517.
https://doi.org/10.1073/pnas.83.19.7513

[41]. King, V. F.; Garcia, M. L.; Shevell, J. L.; Slaughter, R. S.; Kaczorowski, G. J. Substituted Diphenylbutylpiperidines Bind to a Unique High Affinity Site on the L-type Calcium Channel. J. Biol. Chem. 1989, 264 (10), 5633-5641.
https://doi.org/10.1016/S0021-9258(18)83595-5

[42]. Chen, G.; Xia, H.; Cai, Y.; Ma, D.; Yuan, J.; Yuan, C. Synthesis and SAR study of diphenylbutylpiperidines as cell autophagy inducers. Bioorg. amp; Med. Chem. Lett. 2011, 21 (1), 234-239.
https://doi.org/10.1016/j.bmcl.2010.11.029

[43]. Borschberg, H. J. Aristotelia alkaloids: synthetic and biomimetic studies; Elsevier: Amsterdam, 1992; Vol. 11.
https://doi.org/10.1002/chin.199239321

[44]. Borschberg, H. J. The alkaloids: chemistry and pharmacology. Chapt 3; Cordell, G. A., Ed.; Academic Press, Inc: San Diego, 1996.

[45]. Bick, I. C.; Hai, M. A.; Preston, N. W. Isopeduncularine. Tetrahedron 1985, 41 (15), 3127-3130.
https://doi.org/10.1016/S0040-4020(01)96665-7

[46]. Ung, A. T.; Williams, S. G.; Angeloski, A.; Ashmore, J.; Kuzhiumparambil, U.; Bhadbhade, M.; Bishop, R. Formation of 3-azabicyclo[3.3.1]non-3-enes: imino amides vs. imino alkenes. Monatsh Chem 2014, 145 (6), 983-992.
https://doi.org/10.1007/s00706-014-1185-x

[47]. Williams, S. G.; Bhadbhade, M.; Bishop, R.; Ung, A. T. An alkaloid-like 3-azabicyclo[3.3.1]non-3-ene library obtained from the bridged Ritter reaction. Tetrahedron 2017, 73 (2), 116-128.
https://doi.org/10.1016/j.tet.2016.11.057

[48]. Xu, X.; Rawling, T.; Roseblade, A.; Bishop, R.; Ung, A. T. Antiproliferative activities of alkaloid-like compounds. Med. Chem. Commun. 2017, 8 (11), 2105-2114.
https://doi.org/10.1039/C7MD00435D

[49]. Hemtasin, C.; Ung, A. T.; Kanokmedhakul, S.; Kanokmedhakul, K.; Bishop, R.; Satraruji, T.; Bishop, D. Synthesis of alkaloid-like compounds via the bridging Ritter reaction. Monatsh Chem 2012, 143 (6), 955-963.
https://doi.org/10.1007/s00706-012-0759-8

[50]. Sutherland, F.; de Jager, A.; Badenhorst, D.; Scanes, T.; Hundt, H.; Swart, K.; Hundt, A. Sensitive liquid chromatography-tandem mass spectrometry method for the determination of loratadine and its major active metabolite descarboethoxyloratadine in human plasma. J. Chromatogr. A 2001, 914 (1-2), 37-43.
https://doi.org/10.1016/S0021-9673(01)00646-X

[51]. Yang, L.; Clement, R. P.; Kantesaria, B.; Reyderman, L.; Beaudry, F.; Grandmaison, C.; Di Donato, L.; Masse, R.; Rudewicz, P. J. Validation of a sensitive and automated 96-well solid-phase extraction liquid chromatography-tandem mass spectrometry method for the determination of desloratadine and 3-hydroxydesloratadine in human plasma. J. Chromatogr. B 2003, 792 (2), 229-240.
https://doi.org/10.1016/S1570-0232(03)00267-8

[52]. El-Sherbiny, D. T.; El-Enany, N.; Belal, F. F.; Hansen, S. H. Simultaneous determination of loratadine and desloratadine in pharmaceutical preparations using liquid chromatography with a microemulsion as eluent. J. Pharm. Biomed. Anal. 2007, 43 (4), 1236-1242.
https://doi.org/10.1016/j.jpba.2006.10.027

[53]. Vlase, L.; Imre, S.; Muntean, D.; Leucuta, S. E. Determination of loratadine and its active metabolite in human plasma by high-performance liquid chromatography with mass spectrometry detection. J. Pharm. Biomed. Anal. 2007, 44 (3), 652-657.
https://doi.org/10.1016/j.jpba.2006.08.013

[54]. Tian, L.; Li, J.; Wu, K. Synthesis of 3-Hydroxy Desloratadine, the Hydroxyl Metabolite of Loratadine. J. Chem. Pharm. Res. 2014, 6 (3), 982-987. https://www.jocpr.com/articles/synthesis-of-3hydroxy-desloratadine-the-hydroxyl-metabolite-of-loratadine.pdf

[55]. Reddy, K. An efficient method for the conversion of aromatic and aliphatic nitriles to the corresponding N-tert-butyl amides: a modified Ritter reaction. Tetrahedron Lett. 2003, 44 (7), 1453-1455.
https://doi.org/10.1016/S0040-4039(03)00006-6

[56]. Gashkova, O. V.; Mikhailovskii, A. G.; Rudakova, I. P.; Starkova, A. V.; Yusov, A. S. Synthesis and Antiarrhythmic and Hemostatic Activity of [3,3-Dialkyl-3, 4-Dihydroisoquinolin-1(2H )-Ylidene]-N-Alkylacetamides. Pharm Chem J. 2019, 53 (6), 507-510.
https://doi.org/10.1007/s11094-019-02028-6

[57]. Surikova, O. V.; Mikhailovskii, A. G.; Syropyatov, B. Y.; Vakhrin, M. I. Synthesis, Anthelmintic, and Insecticidal Activity of 2-(3-Methyl-6-Methoxy-7-Ethoxy-3,4-Dihydroisoquinolyl-1)Ethanoic Acid Amides. Pharm Chem J. 2015, 48 (10), 665-668.
https://doi.org/10.1007/s11094-015-1166-3

[58]. Bolsakova, J.; Jirgensons, A. The Ritter reaction for the synthesis of heterocycles. Chem Heterocycl Comp 2017, 53 (11), 1167-1177.
https://doi.org/10.1007/s10593-018-2189-y

[59]. Knochel, P.; Molander, G. A. Comprehensive Organic Synthesis; Newnes: Oxford, England, 2014.

[60]. Perevoshchikova, A. N.; Eroshenko, D. V.; Dmitriev, M. V.; Grishko, V. V.; Shklyaev, Y. V. Synthesis and Prediction of the Ubiquinol‐cytochrome c Reductase Inhibitory Activity of 3,4‐Dihydroisoquinolines and 2‐Azaspiro[4.5]decanes (Spiropyrrolines). Journal of Heterocyclic Chem 2019, 56 (5), 1634-1645.
https://doi.org/10.1002/jhet.3551

[61]. Shklyaev, Y. V.; Rozhkova, Y. S.; Perevoshchikova, A. N.; Gorbunov, A. A. Regioselective synthesis of 1-substituted 6-methoxy-3,3,4,4-tetramethyl-3,4-dihydroisoquinolines via Ritter reaction. Russ Chem Bull 2014, 63 (9), 2087-2091.
https://doi.org/10.1007/s11172-014-0706-4

[62]. Perevoshchikova, A. N.; Gilev, M. Yu.; Rozhkova, Yu. S.; Shklyaev, Yu. V. Simple synthesis of 1-substituted 3,3,4,4-tetramethyl-3,4-dihydroisoquinolines. Izv. Vyssh. Uchebn. Zaved., Khim. Khim. Tekhnol. 2015, 58 (3), 12-14. ISSN 0579-2991. https://journals.isuct.ru/public/journals/2/2015/v58_n03_2015_full.pdf (accessed January 13, 2026).

[63]. Perevoshchikova, A. N.; Gorbunov, A. A.; Rozhkova, Y. S.; Slepukhin, P. A.; Shklyaev, Y. V. Synthesis of 1′-substituted 4′,4′-dimethyl-6′-methoxy-4′H-spiro[cyclohexane-1,3′-isoquinolines]. Russ J. Org Chem 2014, 50 (4), 513-517.
https://doi.org/10.1134/S1070428014040125

[64]. Mavroeidi, V.; Shaw, M. Sensitivity distributions and cross-resistance patterns of Mycosphaerella graminicola to fluquinconazole, prochloraz and azoxystrobin over a period of 9 years. Crop Prot. 2005, 24 (3), 259-266.
https://doi.org/10.1016/j.cropro.2004.07.014

[65]. Barton, V.; Fisher, N.; Biagini, G. A.; Ward, S. A.; O'Neill, P. M. Inhibiting Plasmodium cytochrome bc1: a complex issue. Curr. Opin. Chem. Biol. 2010, 14 (4), 440-446.
https://doi.org/10.1016/j.cbpa.2010.05.005

[66]. Davies, W. L.; Grunert, R. R.; Haff, R. F.; McGahen, J. W.; Neumayer, E. M.; Paulshock, M.; Watts, J. C.; Wood, T. R.; Hermann, E. C.; Hoffmann, C. E. Antiviral Activity of 1-Adamantanamine (Amantadine). Science 1964, 144 (3620), 862-863.
https://doi.org/10.1126/science.144.3620.862

[67]. Hubsher, G.; Haider, M.; Okun, M. Amantadine. Neurology 2012, 78 (14), 1096-1099.
https://doi.org/10.1212/WNL.0b013e31824e8f0d

[68]. Vu, D. B.; Nguyen, T. V.; Le, S. T.; Phan, C. D. An Improved Synthesis of Amantadine Hydrochloride. Org. Process Res. Dev. 2017, 21 (11), 1758-1760.
https://doi.org/10.1021/acs.oprd.7b00242

[69]. Ung, A. T.; West, A. N.; Phillips, M. J.; Williams, S. G. Synthesis of alkaloid-like compounds via the bridging Ritter reactions II. Monatsh Chem 2016, 147 (10), 1737-1746.
https://doi.org/10.1007/s00706-016-1817-4

[70]. Chackalamannil, S.; Xia, Y. Thrombin receptor (PAR-1) antagonists as novel antithrombotic agents. Expert Opin. Ther. Pat. 2006, 16 (4), 493-505.
https://doi.org/10.1517/13543776.16.4.493

[71]. Ramachandran, R.; Noorbakhsh, F.; DeFea, K.; Hollenberg, M. D. Targeting proteinase-activated receptors: therapeutic potential and challenges. Nat Rev Drug Discov 2012, 11 (1), 69-86.
https://doi.org/10.1038/nrd3615

[72]. Chelliah, M. V.; Eagen, K.; Guo, Z.; Chackalamannil, S.; Xia, Y.; Tsai, H.; Greenlee, W. J.; Ahn, H.; Kurowski, S.; Boykow, G.; Hsieh, Y.; Chintala, M. Himbacine-Derived Thrombin Receptor Antagonists: C7-Spirocyclic Analogues of Vorapaxar. ACS. Med. Chem. Lett. 2014, 5 (5), 561-565.
https://doi.org/10.1021/ml500008w

[73]. Flick, A. C.; Ding, H. X.; Leverett, C. A.; Kyne, R. E.; Liu, K. K.; Fink, S. J.; O'Donnell, C. J. Synthetic approaches to the 2014 new drugs. Bioorg. amp; Med. Chem. 2016, 24 (9), 1937-1980.
https://doi.org/10.1016/j.bmc.2016.03.004

[74]. Park, C. M.; Lee, S.; Song, J.; Lee, J. Discovery of (E)‐5,5‐Difluoro‐1‐[2‐[5‐(3‐fluorophenyl)pyridin‐2‐yl]vinyl]octahydrospiro(indene‐2,5′‐oxazolidin)‐2′‐one as a PAR1 Antagonist. Bulletin Korean Chem Soc 2019, 40 (7), 658-667.
https://doi.org/10.1002/bkcs.11747

[75]. Xu, X.; Roseblade, A.; Rawling, T.; Ung, A. T. Antiproliferative activities of tricyclic amides derived from β-caryophyllene via the Ritter reaction against MDA-MB-231 breast cancer cells. RSC. Med. Chem. 2020, 11 (1), 118-124.
https://doi.org/10.1039/C9MD00237E

[76]. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease: 2024 Report; GOLD: 2024. Available at: https://goldcopd.org/wp-content/uploads/2024/01/GOLD-2024_v1.2-11Jan24_WMV-1.pdf (accessed June 31, 2026).

[77]. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease: 2017 Report; GOLD, 2017. https://goldcopd.org/wp-content/uploads/2017/02/wms-GOLD-2017-FINAL.pdf (accessed June 31, 2026).

[78]. Barnes, P. J. Immunology of asthma and chronic obstructive pulmonary disease. Nat Rev Immunol 2008, 8 (3), 183-192.
https://doi.org/10.1038/nri2254

[79]. Yi, C.; Xing, G.; Wang, S.; Li, X.; Liu, Y.; Li, J.; Lin, B.; Woo, A. Y.; Zhang, Y.; Pan, L.; Cheng, M. Design, synthesis and biological evaluation of 8-(2-amino-1-hydroxyethyl)-6-hydroxy-1,4-benzoxazine-3(4H)-one derivatives as potent β2-adrenoceptor agonists. Bioorg. amp; Med. Chem. 2020, 28 (1), 115178.
https://doi.org/10.1016/j.bmc.2019.115178

[80]. Zeng, J.; Jiang, Y.; Liu, J. Analysis of the armyworm outbreak in 2012 and suggestions of monitoring and forecasting Plant Prot. 2013, 39 (2), 117-121.

[81]. Sparks, T. C.; Nauen, R. IRAC: Mode of action classification and insecticide resistance management. Pestic. Biochem. Physiol. 2015, 121, 122-128.
https://doi.org/10.1016/j.pestbp.2014.11.014

[82]. Nauen, R.; Slater, R.; Sparks, T. C.; Elbert, A.; Mccaffery, A. IRAC Insecticide Resistance and Mode‐of‐action Classification of Insecticides. Mod. Crop Prot. Compd. 2019, 995-1012.
https://doi.org/10.1002/9783527699261.ch28

[83]. Jeschke, P. Progress of modern agricultural chemistry and future prospects. Pest Manag. Sci. 2015, 72 (3), 433-455.
https://doi.org/10.1002/ps.4190

[84]. Xing, G.; Zhi, Z.; Yi, C.; Zou, J.; Jing, X.; Yiu-Ho Woo, A.; Lin, B.; Pan, L.; Zhang, Y.; Cheng, M. 8-Hydroxyquinolin-2(1H)-one analogues as potential β2-agonists: Design, synthesis and activity study. Eur. J. Med. Chem. 2021, 224, 113697.
https://doi.org/10.1016/j.ejmech.2021.113697

[85]. Du, Y.; Lunga, A.; Rubtsov, A. E.; Malkov, A. V. Short electrochemical asymmetric synthesis of (+)-N-acetylcolchinol. Green Chem. 2022, 24 (18), 7220-7226.
https://doi.org/10.1039/D2GC02321K

[86]. Murrough, J. W. Ketamine as a Novel Antidepressant: From Synapse to Behavior. Clin Pharmacol Ther 2011, 91 (2), 303-309.
https://doi.org/10.1038/clpt.2011.244

[87]. Holtmanjr, J.; Crooks, P.; Johnsonhardy, J.; Hojomat, M.; Kleven, M.; Wala, E. Effects of norketamine enantiomers in rodent models of persistent pain. Pharmacol. Biochem. Behav. 2008, 90 (4), 676-685.
https://doi.org/10.1016/j.pbb.2008.05.011

[88]. Paul, R. K.; Singh, N. S.; Khadeer, M.; Moaddel, R.; Sanghvi, M.; Green, C. E.; O'Loughlin, K.; Torjman, M. C.; Bernier, M.; Wainer, I. W. (R,S)-Ketamine Metabolites (R,S)-norketamine and (2S,6S)-hydroxynorketamine Increase the Mammalian Target of Rapamycin Function. Anesthesiology 2014, 121 (1), 149-159.
https://doi.org/10.1097/ALN.0000000000000285

[89]. Biermann, M.; Zheng, G.; Hojahmat, M.; Moskalev, N. V.; Crooks, P. A. Asymmetric synthesis of (S)- and (R)-norketamine via Sharpless asymmetric dihydroxylation/Ritter amination sequence. Tetrahedron Lett. 2015, 56 (20), 2608-2610.
https://doi.org/10.1016/j.tetlet.2015.04.050

[90]. Huang, D.; Wang, H.; Guan, H.; Huang, H.; Shi, Y. An Acid-Catalyzed Formal Allylic C−H Oxidation of Aryl Cycloalkenes with N-Propylthiosuccinimide. Org. Lett. 2011, 13 (6), 1548-1551.
https://doi.org/10.1021/ol200261a

[91]. Toop, H. D.; Dun, M. D.; Ross, B. K.; Flanagan, H. M.; Verrills, N. M.; Morris, J. C. Development of novel PP2A activators for use in the treatment of acute myeloid leukaemia. Org. Biomol. Chem. 2016, 14 (20), 4605-4616.
https://doi.org/10.1039/C6OB00556J

[92]. Alliot, J.; Theodorou, I.; Ducongé, F.; Gravel, E.; Doris, E. Polyamine transport system-targeted nanometric micelles assembled from epipodophyllotoxin-amphiphiles. Chem. Commun. 2019, 55 (99), 14968-14971.
https://doi.org/10.1039/C9CC07883E

[93]. Zhang, Y.; Chen, S.; Liu, Y.; Wang, Q. Route Evaluation and Ritter Reaction Based Synthesis of Oxazoline Acaricide Candidates FET-II-L and NK-12. Org. Process Res. Dev. 2020, 24 (2), 216-227.
https://doi.org/10.1021/acs.oprd.9b00494

[94]. Calverley, P. M.; Anderson, J. A.; Celli, B.; Ferguson, G. T.; Jenkins, C.; Jones, P. W.; Yates, J. C.; Vestbo, J. Salmeterol and Fluticasone Propionate and Survival in Chronic Obstructive Pulmonary Disease. N. Engl J. Med 2007, 356 (8), 775-789.
https://doi.org/10.1056/NEJMoa063070

[95]. Hanania, N. A.; Papi, A.; Anzueto, A.; Martinez, F. J.; Rossman, K. A.; Cappelletti, C. S.; Duncan, E. A.; Nyberg, J. S.; Dorinsky, P. M. Efficacy and safety of two doses of budesonide/formoterol fumarate metered dose inhaler in COPD. ERJ. Open Res 2020, 6 (2), 00187-2019.
https://doi.org/10.1183/23120541.00187-2019

[96]. Chavan, R. R.; Hosamani, K. M.; Kulkarni, B. D.; Joshi, S. D. Molecular docking studies and facile synthesis of most potent biologically active N-tert-butyl-4-(4-substituted phenyl)-2-((substituted-2-oxo-2H-chromen-4-yl)methylthio)-6-oxo-1,6-dihydropyrimidine-5-carboxamide hybrids: An approach for microwave-assisted syntheses and biological evaluation. Bioorg. Chem. 2018, 78, 185-194.
https://doi.org/10.1016/j.bioorg.2018.03.007

[97]. Baenziger, M.; Mak, C.; Muehle, H.; Nobs, F.; Prikoszovich, W.; Reber, J.; Sunay, U. Practical Synthesis of 8α-Amino-2,6-dimethylergoline: An Industrial Perspective. Org. Process Res. Dev. 1997, 1 (6), 395-406.
https://doi.org/10.1021/op9700284

[98]. Waldvogel, E.; Engeli, P.; Küsters, E. Total synthesis of 2,6‐dimethylergolin‐8α‐amines. Helv. Chim. Acta 1997, 80 (7), 2084-2099.
https://doi.org/10.1002/hlca.19970800709

[99]. Wong, F.; Yeh, M.; Chang, E.; Chen, T.; Chang, E. Convenient and Efficient Synthesis of Pyrazole-Based DHODase Inhibitors from 3-Aryl-4-cyanosydnone. Synlett 2006, 2006 (06), 901-904.
https://doi.org/10.1055/s-2006-939041

[100]. Getman, D. P.; DeCrescenzo, G. A.; Heintz, R. M.; Reed, K. L.; Talley, J. J.; Bryant, M. L.; Clare, M.; Houseman, K. A.; Marr, J. J. Discovery of a novel class of potent HIV-1 protease inhibitors containing the (R)-(hydroxyethyl)urea isostere. J. Med. Chem. 1993, 36 (2), 288-291.
https://doi.org/10.1021/jm00054a014

[101]. Parkes, K. E.; Bushnell, D. J.; Crackett, P. H.; Dunsdon, S. J.; Freeman, A. C.; Gunn, M. P.; Hopkins, R. A.; Lambert, R. W.; Martin, J. A. Studies toward the Large-Scale Synthesis of the HIV Proteinase Inhibitor Ro 31-8959. J. Org. Chem. 1994, 59 (13), 3656-3664.
https://doi.org/10.1021/jo00092a026

[102]. Beaulieu, P. L.; Wernic, D. Preparation of Aminoalkyl Chlorohydrin Hydrochlorides: Key Building Blocks for Hydroxyethylamine-Based HIV Protease Inhibitors. J. Org. Chem. 1996, 61 (11), 3635-3645.
https://doi.org/10.1021/jo960109i

[103]. Reid, R. C.; March, D. R.; Dooley, M. J.; Bergman, D. A.; Abbenante, G.; Fairlie, D. P. A Novel Bicyclic Enzyme Inhibitor as a Consensus Peptidomimetic for the Receptor-Bound Conformations of 12 Peptidic Inhibitors of HIV-1 Protease. J. Am. Chem. Soc. 1996, 118 (36), 8511-8517.
https://doi.org/10.1021/ja960433v

[104]. Beaulieu, P. L.; Lavallée, P.; Abraham, ; Anderson, P. C.; Boucher, C.; Bousquet, Y.; Duceppe, J.; Gillard, J.; Gorys, V.; Grand-Maître, C.; Grenier, L.; Guindon, Y.; Guse, I.; Plamondon, L.; Soucy, F.; Valois, S.; Wernic, D.; Yoakim, C. Practical, Stereoselective Synthesis of Palinavir, a Potent HIV Protease Inhibitor. J. Org. Chem. 1997, 62 (11), 3440-3448.
https://doi.org/10.1021/jo9702655

[105]. Concellón, J. M.; Suárez, J. R.; del Solar, V. Regioselective Ring Opening of Amino Epoxides with Nitriles: An Easy Synthesis of (2R,3S)- and (2S,3S)-1,3-Diaminoalkan-2-ols with Differently Protected Amine Functions. J. Org. Chem. 2005, 70 (18), 7447-7450.
https://doi.org/10.1021/jo051109y

[106]. Dos Santos, M.; Crousse, B.; Bonnet-Delpon, D. Improved Ritter reaction with CF3-containing oxirane for an access to central units of protease inhibitors. Tetrahedron Lett. 2009, 50 (8), 857-859.
https://doi.org/10.1016/j.tetlet.2008.09.170

[107]. Chatterjee, A.; Bose, S.; Srimany, S. K. Studies on the Constitution, Stereochemistry, and Synthesis of Aegeline,1 an Alkaloidal-Amide of Aegle marmelos Correa. J. Org. Chem. 1959, 24 (5), 687-690.
https://doi.org/10.1021/jo01087a034

[108]. Narender, T.; Shweta, S.; Tiwari, P.; Papi Reddy, K.; Khaliq, T.; Prathipati, P.; Puri, A.; Srivastava, A.; Chander, R.; Agarwal, S.; Raj, K. Antihyperglycemic and antidyslipidemic agent from Aegle marmelos. Bioorg. amp; Med. Chem. Lett. 2007, 17 (6), 1808-1811.
https://doi.org/10.1016/j.bmcl.2006.12.037

[109]. Sarkar, S.; Sonkar, R.; Bhatia, G.; Tadigoppula, N. Synthesis of new N-acryl-1-amino-2-phenylethanol and N-acyl-1-amino-3-aryloxypropanols and evaluation of their antihyperlipidemic, LDL-oxidation and antioxidant activity. Eur. J. Med. Chem. 2014, 80, 135-144.
https://doi.org/10.1016/j.ejmech.2014.04.020

[110]. Rajan, S.; Satish, S.; Shankar, K.; Pandeti, S.; Varshney, S.; Srivastava, A.; Kumar, D.; Gupta, A.; Gupta, S.; Choudhary, R.; Balaramnavar, V. M.; Narender, T.; Gaikwad, A. N. Aegeline inspired synthesis of novel β3-AR agonist improves insulin sensitivity in vitro and in vivo models of insulin resistance. Metabolism 2018, 85, 1-13.
https://doi.org/10.1016/j.metabol.2018.03.001

[111]. Jiang, D.; He, T.; Ma, L.; Wang, Z. Recent developments in Ritter reaction. RSC Adv, 2014, 4 (110), 64936-64946.
https://doi.org/10.1039/C4RA10784E

[112]. Liu, C.; Zhang, Q.; Li, H.; Guo, S.; Xiao, B.; Deng, W.; Liu, L.; He, W. Cu/Fe Catalyzed Intermolecular Oxidative Amination of Benzylic C−H Bonds. Chemistry A. European J. 2016, 22 (18), 6208-6212.
https://doi.org/10.1002/chem.201600107

[113]. Ben-Ari, Y. Excitatory actions of gaba during development: the nature of the nurture. Nat Rev Neurosci 2002, 3 (9), 728-739.
https://doi.org/10.1038/nrn920

[114]. Ben-Ari, Y.; Gaiarsa, J.; Tyzio, R.; Khazipov, R. GABA: A Pioneer Transmitter That Excites Immature Neurons and Generates Primitive Oscillations. Physiol. Rev. 2007, 87 (4), 1215-1284.
https://doi.org/10.1152/physrev.00017.2006

[115]. Huang, Y.; Mucke, L. Alzheimer Mechanisms and Therapeutic Strategies. Cell 2012, 148 (6), 1204-1222.
https://doi.org/10.1016/j.cell.2012.02.040

[116]. Rudolph, U.; Mohler, H. GABA-based therapeutic approaches: GABAA receptor subtype functions. Curr. Opin. Pharmacol. 2006, 6 (1), 18-23.
https://doi.org/10.1016/j.coph.2005.10.003

[117]. Gajcy, K.; Lochynski, S.; Librowski, T. A Role of GABA Analogues in the Treatment of Neurological Diseases. CMC. 2010, 17 (22), 2338-2347.
https://doi.org/10.2174/092986710791698549

[118]. Zhu, N.; Wang, T.; Ge, L.; Li, Y.; Zhang, X.; Bao, H. γ-Amino Butyric Acid (GABA) Synthesis Enabled by Copper-Catalyzed Carboamination of Alkenes. Org. Lett. 2017, 19 (18), 4718-4721.
https://doi.org/10.1021/acs.orglett.7b01969

[119]. Peng, X.; Sun, Z.; Kuang, P.; Li, L.; Chen, J.; Chen, J. Copper-Catalyzed Selective Arylation of Nitriles with Cyclic Diaryl Iodonium Salts: Direct Access to Structurally Diversified Diarylmethane Amides with Potential Neuroprotective and Anticancer Activities. Org. Lett. 2020, 22 (15), 5789-5795.
https://doi.org/10.1021/acs.orglett.0c01829

[120]. Wang, Z. D.; Sheikh, S. O.; Cox, S.; Zhang, Y.; Massey, K. Direct Preparation of N‐Glycosidic Bond‐Linked Nonionic Carbohydrate‐Based Surfactant (NICBS) via Ritter Reaction. Eur J. Org Chem 2007, 2007 (14), 2243-2247.
https://doi.org/10.1002/ejoc.200700079

[121]. Rubenbauer, P.; Bach, T. Diastereoselective Ritter reactions of chiral secondary benzylic alcohols. Chem. Commun. 2009, 2130.
https://doi.org/10.1039/b901937e

[122]. Meyers, A. I.; Reider, P. J. Stereoselective synthesis of threo-3-hydroxy-2-methylcarboxylic acids using alkoxyalkyl propionates. J. Am. Chem. Soc. 1979, 101 (9), 2501-2502.
https://doi.org/10.1021/ja00503a052

[123]. Denmark, S. E.; Griedel, B. D.; Coe, D. M.; Schnute, M. E. Chemistry of Enoxysilacyclobutanes: Highly Selective Uncatalyzed Aldol Additions. J. Am. Chem. Soc. 1994, 116 (16), 7026-7043.
https://doi.org/10.1021/ja00095a004

[124]. Sanz, R.; Martínez, A.; Guilarte, V.; Álvarez‐Gutiérrez, J. M.; Rodríguez, F. The Ritter Reaction under Truly Catalytic Brønsted Acid Conditions. Eur J. Org Chem 2007, 2007 (28), 4642-4645.
https://doi.org/10.1002/ejoc.200700562

[125]. Soliman, H. A.; Mubarak, A. Y.; El-Mekabaty, A.; Awad, H. M.; Elmorsy, S. S. Eco-friendly synthesis of amidochloroalkylnaphthols and its related oxazepinones with biological evaluation. Monatsh Chem 2015, 147 (4), 809-816.
https://doi.org/10.1007/s00706-015-1536-2

[126]. Feng, C.; Yan, B.; Yao, W.; Chen, J.; Ji, M. Zn(ClO4)26H2O‐Catalyzed One‐Pot Synthesis of Amides via Ritter Reaction with Alcohols, Acetic Anhydride and Nitriles. ChemistrySelect 2018, 3 (42), 11775-11778.
https://doi.org/10.1002/slct.201802386

[127]. Stocker, B. L.; Dangerfield, E. M.; Win‐Mason, A. L.; Haslett, G. W.; Timmer, M. S. Recent Developments in the Synthesis of Pyrrolidine‐Containing Iminosugars. Eur J. Org Chem 2010, 2010 (9), 1615-1637.
https://doi.org/10.1002/ejoc.200901320

[128]. Compain, P.; Martin, O. Design, Synthesis and Biological Evaluation of Iminosugar-Based Glycosyltransferase Inhibitors. CTMC. 2003, 3 (5), 541-560.
https://doi.org/10.2174/1568026033452474

[129]. Watson, A. A.; Fleet, G. W.; Asano, N.; Molyneux, R. J.; Nash, R. J. Polyhydroxylated alkaloids - natural occurrence and therapeutic applications. Phytochemistry 2001, 56 (3), 265-295.
https://doi.org/10.1016/S0031-9422(00)00451-9

[130]. Asano, N.; Nash, R. J.; Molyneux, R. J.; Fleet, G. W. Sugar-mimic glycosidase inhibitors: natural occurrence, biological activity and prospects for therapeutic application. Tetrahedron: Asymmetry 2000, 11 (8), 1645-1680.
https://doi.org/10.1016/S0957-4166(00)00113-0

[131]. El-Nezhawy, A. O.; Alrobaian, M.; Khames, A.; El-Badawy, M. F.; Abdelwahab, S. F. Design and total synthesis of (-)-codonopsinine, (-)-codonopsine and codonopsinine analogues by O-(2-oxopyrrolidin-5-yl)trichloroacetimidate as amidoalkylating agent with improved antimicrobial activity via solid lipid nanoparticle formulations. Bioorg. amp; Med. Chem. 2019, 27 (7), 1263-1273.
https://doi.org/10.1016/j.bmc.2019.02.021

[132]. Dow, R. L. β3-adrenergic agonists: potential therapeutics for obesity. Expert Opin. Investig. Drugs 1997, 6 (12), 1811-1825.
https://doi.org/10.1517/13543784.6.12.1811

[133]. Weber, A. E. β3 Adrenergic Receptor Agonists for the Treatment of Obesity. Annu. Rep. Med. Chem. 1998, 193-202.
https://doi.org/10.1016/S0065-7743(08)61084-2

[134]. Lafontaine, J. A.; Day, R. F.; Dibrino, J.; Hadcock, J. R.; Hargrove, D. M.; Linhares, M.; Martin, K. A.; Maurer, T. S.; Nardone, N. A.; Tess, D. A.; DaSilva-Jardine, P. Discovery of potent and orally bioavailable heterocycle-based β3-adrenergic receptor agonists, potential therapeutics for the treatment of obesity. Bioorg. amp; Med. Chem. Lett. 2007, 17 (18), 5245-5250.
https://doi.org/10.1016/j.bmcl.2007.06.072

[135]. Imanishi, M.; Tomishima, Y.; Itou, S.; Hamashima, H.; Nakajima, Y.; Washizuka, K.; Sakurai, M.; Matsui, S.; Imamura, E.; Ueshima, K.; Yamamoto, T.; Yamamoto, N.; Ishikawa, H.; Nakano, K.; Unami, N.; Hamada, K.; Matsumura, Y.; Takamura, F.; Hattori, K. Discovery of a Novel Series of Biphenyl Benzoic Acid Derivatives as Potent and Selective Human β3-Adrenergic Receptor Agonists with Good Oral Bioavailability. Part I. J. Med. Chem. 2008, 51 (6), 1925-1944.
https://doi.org/10.1021/jm701324c

[136]. Tanaka, N.; Tamai, T.; Mukaiyama, H.; Hirabayashi, A.; Muranaka, H.; Ishikawa, T.; Kobayashi, J.; Akahane, S.; Akahane, M. Relationship between Stereochemistry and the β3-Adrenoceptor Agonistic Activity of 4'-Hydroxynorephedrine Derivative as an Agent for Treatment of Frequent Urination and Urinary Incontinence. J. Med. Chem. 2002, 46 (1), 105-112.
https://doi.org/10.1021/jm020177z

[137]. Bradley, P. A.; Carroll, R. J.; Lecouturier, Y. C.; Moore, R.; Noeureuil, P.; Patel, B.; Snow, J.; Wheeler, S. The Synthesis of Two Potent β-3 Adrenergic Receptor Agonists. Org. Process Res. Dev. 2010, 14 (6), 1326-1336.
https://doi.org/10.1021/op1001462

[138]. Ratnakar Reddy, K.; Poornachandra, Y.; Jitender Dev, G.; Mallareddy, G.; Nanubolu, J. B.; Kumar, C. G.; Narsaiah, B. Synthesis of novel amide functionalized 2H-chromene derivatives by Ritter amidation of primary alcohol using HBF4·OEt2 as a mild and versatile reagent and evaluation of their antimicrobial and anti-biofilm activities. Bioorg. amp; Med. Chem. Lett. 2015, 25 (15), 2943-2947.
https://doi.org/10.1016/j.bmcl.2015.05.041

[139]. Li, H.; Cai, L.; Li, J.; Hu, Y.; Zhou, P.; Zhang, J. Novel coumarin fluorescent dyes: Synthesis, structural characterization and recognition behavior towards Cu(II) and Ni(II). Dyes Pigments 2011, 91 (3), 309-316.
https://doi.org/10.1016/j.dyepig.2011.05.011

[140]. Ferm, R. J.; Riebsomer, J. L. The Chemistry of the 2-Imidazolines and Imidazolidines.. Chem. Rev. 1954, 54 (4), 593-613.
https://doi.org/10.1021/cr60170a002

[141]. Luca, L. D. Naturally Occurring and Synthetic Imidazoles: Their Chemistry and Their Biological Activities. Curr Med Chem 2006, 13 (1), 1-23.
https://doi.org/10.2174/092986706775197971

[142]. Weinreb, S. M. Some recent advances in the synthesis of polycyclic imidazole-containing marine natural products. Nat. Prod. Rep. 2007, 24 (5), 931.
https://doi.org/10.1039/b700206h

[143]. Wiglenda, T.; Gust, R. Structure−Activity Relationship Study To Understand the Estrogen Receptor-Dependent Gene Activation of Aryl- and Alkyl-Substituted 1H-Imidazoles. J. Med. Chem. 2007, 50 (7), 1475-1484.
https://doi.org/10.1021/jm061106t

[144]. Xiao, M.; Ahn, S.; Wang, J.; Chen, J.; Miller, D. D.; Dalton, J. T.; Li, W. Discovery of 4-Aryl-2-benzoyl-imidazoles as Tubulin Polymerization Inhibitor with Potent Antiproliferative Properties. J. Med. Chem. 2013, 56 (8), 3318-3329.
https://doi.org/10.1021/jm4001117

[145]. Sarnpitak, P.; Mujumdar, P.; Morisseau, C.; Hwang, S. H.; Hammock, B.; Iurchenko, V.; Zozulya, S.; Gavalas, A.; Geronikaki, A.; Ivanenkov, Y.; Krasavin, M. Potent, orally available, selective COX-2 inhibitors based on 2-imidazoline core. Eur. J. Med. Chem. 2014, 84, 160-172.
https://doi.org/10.1016/j.ejmech.2014.07.023

[146]. Krasavin, M. Biologically active compounds based on the privileged 2-imidazoline scaffold: The world beyond adrenergic/imidazoline receptor modulators. Eur. J. Med. Chem. 2015, 97, 525-537.
https://doi.org/10.1016/j.ejmech.2014.11.028

[147]. Sączewski, F.; Kornicka, A.; Balewski, L. Imidazoline scaffold in medicinal chemistry: a patent review (2012-2015). Expert Opin. Ther. Pat. 2016, 26 (9), 1031-1048.
https://doi.org/10.1080/13543776.2016.1210128

[148]. Krasavin, M. N-(Hetero)aryl-2-imidazolines: an emerging privileged motif for contemporary drug design. Chem Heterocycl Comp 2017, 53 (3), 240-255.
https://doi.org/10.1007/s10593-017-2047-3

[149]. Bazanov, D. R.; Pervushin, N. V.; Savin, E. V.; Tsymliakov, M. D.; Maksutova, A. I.; Savitskaya, V. Y.; Sosonyuk, S. E.; Gracheva, Y. A.; Seliverstov, M. Y.; Lozinskaya, N. A.; Kopeina, G. S. Synthetic Design and Biological Evaluation of New p53-MDM2 Interaction Inhibitors Based on Imidazoline Core. Pharmaceuticals 2022, 15 (4), 444.
https://doi.org/10.3390/ph15040444

[150]. Smorodina, A. A.; Buev, E. M.; Moshkin, V. S.; Sosnovskikh, V. Y. Arylethanolamines in Ritter reaction: Synthesis of 2,4‐Diarylimidazole Core. Asian J. Org Chem 2023, 12 (2), e202200656 https://doi.org/10.1002/ajoc.202200656.
https://doi.org/10.1002/ajoc.202200656

Most read articles by the same author(s)

TrendMD

Dimensions - Altmetric - scite_ - PlumX

Downloads and views

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

License Terms

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

License Terms

by-nc

Copyright © 2026 by Authors. This work is published and licensed by Atlanta Publishing House LLC, Atlanta, GA, USA. The full terms of this license are available at https://www.eurjchem.com/index.php/eurjchem/terms and incorporate the Creative Commons Attribution-Non Commercial (CC BY NC) (International, v4.0) License (http://creativecommons.org/licenses/by-nc/4.0). By accessing the work, you hereby accept the Terms. This is an open access article distributed under the terms and conditions of the CC BY NC License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited without any further permission from Atlanta Publishing House LLC (European Journal of Chemistry). No use, distribution, or reproduction is permitted which does not comply with these terms. Permissions for commercial use of this work beyond the scope of the License (https://www.eurjchem.com/index.php/eurjchem/terms) are administered by Atlanta Publishing House LLC (European Journal of Chemistry).

Article Sidebar

Main Article Content

Abstract

Article Details

Downloads

Metrics