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Current Topics in Medicinal Chemistry

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ISSN (Online): 1873-4294

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Highlights on Fluorine-containing Drugs Approved by U.S. FDA in 2023

Author(s): Saghir Ali, Andrew A. Bolinger and Jia Zhou*

Volume 24, Issue 10, 2024

Published on: 05 March, 2024

Page: [843 - 849] Pages: 7

DOI: 10.2174/0115680266300245240223070242

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Abstract

Fluorine continues to show its potential applications in drug discovery and development, as reflected by twelve drugs being fluorinated out of the fifty-five approved by the FDA in 2023. This concise review highlights the discovery of each of these fluorine-containing drugs in the past year, including its brand name, date of approval, composition, sponsors, indication, and mechanism of action. The relevant future trend is also briefly discussed.

Keywords: Fluorine, FDA approval, Fluorinated drugs, Small-molecule drug discovery, Diagnostic tools, Therapeutics.

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[1]
Roesky, H.W.; Sharpless, K.B. Efficient Preparations of Fluorine Compounds, 1st ed; Wiley: Chichester, 2012.
[http://dx.doi.org/10.1002/9781118409466]
[2]
Müller, K.; Faeh, C.; Diederich, F. Fluorine in pharmaceuticals: Looking beyond intuition. Science, 2007, 317(5846), 1881-1886.
[http://dx.doi.org/10.1126/science.1131943] [PMID: 17901324]
[3]
Godhaviya, P.K. Studies of Fluorine: History, Application, water Fluoridation, Organo Fluorine, 1st ed; CreateSpace Independent Publishing Platform, 2015.
[4]
Groult, H.; Leroux, F.; Tressaud, A. Modern Synthesis Processes and Reactivity of Fluorinated Compounds: Progress in Fluorine Science, 1st ed; Elsevier: Amsterdam, 2016.
[5]
Haufe, G.; Leroux, F. Fluorine in Life Sciences: Pharmaceuticals, Medicinal Diagnostics, and Agrochemicals: Progress in Fluorine Science Series, 1st ed; Academic Press, 2018.
[6]
Fang, C.; Jing, Y.; Zong, Y.; Lin, Z. Preparation and characterization of fluorine-containing acrylic latex PSAs using a reactive surfactant. J. Fluor. Chem., 2016, 192, 113-119.
[http://dx.doi.org/10.1016/j.jfluchem.2016.10.021]
[7]
Hong, H.; Zhang, L.; Xie, F.; Zhuang, R.; Jiang, D.; Liu, H.; Li, J.; Yang, H.; Zhang, X.; Nie, L.; Li, Z. Rapid one-step 18F-radiolabeling of biomolecules in aqueous media by organophosphine fluoride acceptors. Nat. Commun., 2019, 10(1), 989.
[http://dx.doi.org/10.1038/s41467-019-08953-0] [PMID: 30824691]
[8]
Mabuchi, S.; Komura, N.; Sasano, T.; Shimura, K.; Yokoi, E.; Kozasa, K.; Kuroda, H.; Takahashi, R.; Kawano, M.; Matsumoto, Y.; Kato, H.; Hatazawa, J.; Kimura, T. Pretreatment tumor-related leukocytosis misleads positron emission tomography-computed tomography during lymph node staging in gynecological malignancies. Nat. Commun., 2020, 11(1), 1364.
[http://dx.doi.org/10.1038/s41467-020-15186-z] [PMID: 32170086]
[9]
Fu, Y.; Helbert, H.; Simeth, N.A.; Crespi, S.; Spoelstra, G.B.; van Dijl, J.M.; van Oosten, M.; Nazario, L.R.; van der Born, D.; Luurtsema, G.; Szymanski, W.; Elsinga, P.H.; Feringa, B.L. Ultrafast photoclick reaction for selective 18 f-positron emission tomography tracer synthesis in flow. J. Am. Chem. Soc., 2021, 143(27), 10041-10047.
[http://dx.doi.org/10.1021/jacs.1c02229] [PMID: 34181410]
[10]
Duro, M.V.V.; Van Valkenburgh, J.; Ingles, D.E.; Tran, J.; Cai, Z.; Ebright, B.; Wang, S.; Kerman, B.E.; Galvan, J.; Hwang, S.H.; Sta Maria, N.S.; Zanderigo, F.; Croteau, E.; Cunnane, S.C.; Rapoport, S.I.; Louie, S.G.; Jacobs, R.E.; Yassine, H.N.; Chen, K. Synthesis and preclinical evaluation of 22-[ 18 F]fluorodocosahexaenoic acid as a positron emission tomography probe for monitoring brain docosahexaenoic acid uptake kinetics. ACS Chem. Neurosci., 2023, 14(24), 4409-4418.
[http://dx.doi.org/10.1021/acschemneuro.3c00681] [PMID: 38048230]
[11]
Tirotta, I.; Dichiarante, V.; Pigliacelli, C.; Cavallo, G.; Terraneo, G.; Bombelli, F.B.; Metrangolo, P.; Resnati, G. (19)F magnetic resonance imaging (MRI): From design of materials to clinical applications. Chem. Rev., 2015, 115(2), 1106-1129.
[http://dx.doi.org/10.1021/cr500286d] [PMID: 25329814]
[12]
Ahrens, E.T.; Zhong, J. in vivo MRI cell tracking using perfluorocarbon probes and fluorine-19 detection. NMR Biomed., 2013, 26(7), 860-871.
[http://dx.doi.org/10.1002/nbm.2948] [PMID: 23606473]
[13]
Hequet, E.; Henoumont, C.; Muller, R.N.; Laurent, S. Fluorinated MRI contrast agents and their versatile applications in the biomedical field. Future Med. Chem., 2019, 11(10), 1157-1175.
[http://dx.doi.org/10.4155/fmc-2018-0463] [PMID: 31280670]
[14]
Gillis, E.P.; Eastman, K.J.; Hill, M.D.; Donnelly, D.J.; Meanwell, N.A. Applications of fluorine in medicinal chemistry. J. Med. Chem., 2015, 58(21), 8315-8359.
[http://dx.doi.org/10.1021/acs.jmedchem.5b00258] [PMID: 26200936]
[15]
Böhm, H.J.; Banner, D.; Bendels, S.; Kansy, M.; Kuhn, B.; Müller, K.; Obst-Sander, U.; Stahl, M. Fluorine in medicinal chemistry. ChemBioChem, 2004, 5(5), 637-643.
[http://dx.doi.org/10.1002/cbic.200301023] [PMID: 15122635]
[16]
Shah, P.; Westwell, A.D. The role of fluorine in medicinal chemistry. J. Enzyme Inhib. Med. Chem., 2007, 22(5), 527-540.
[http://dx.doi.org/10.1080/14756360701425014] [PMID: 18035820]
[17]
Ali, S.; Zhou, J. Highlights on U.S. FDA-approved fluorinated drugs over the past five years (2018–2022). Eur. J. Med. Chem., 2023, 256, 115476.
[http://dx.doi.org/10.1016/j.ejmech.2023.115476] [PMID: 37207534]
[18]
Keam, S.J. Pirtobrutinib: First approval. Drugs, 2023, 83(6), 547-553.
[http://dx.doi.org/10.1007/s40265-023-01860-1] [PMID: 37004673]
[19]
Telaraja, D.; Kasamon, Y.L.; Collazo, J.S.; Leong, R.; Wang, K.; Li, P.; Dahmane, E.; Yang, Y.; Earp, J.; Grimstein, M.; Rodriguez, L.R.; Theoret, M.R.; Gormley, N.J. FDA approval summary: Pirtobrutinib for relapsed or refractory mantle cell lymphoma. Clin. Cancer Res., 2023.
[PMID: 37624619]
[20]
Jensen, J.L.; Mato, A.R.; Pena, C.; Roeker, L.E.; Coombs, C.C. The potential of pirtobrutinib in multiple B-cell malignancies. Ther. Adv. Hematol., 2022, 13
[http://dx.doi.org/10.1177/20406207221101697] [PMID: 35747462]
[21]
Mato, A.R.; Shah, N.N.; Jurczak, W.; Cheah, C.Y.; Pagel, J.M.; Woyach, J.A.; Fakhri, B.; Eyre, T.A.; Lamanna, N.; Patel, M.R.; Alencar, A.; Lech-Maranda, E.; Wierda, W.G.; Coombs, C.C.; Gerson, J.N.; Ghia, P.; Le Gouill, S.; Lewis, D.J.; Sundaram, S.; Cohen, J.B.; Flinn, I.W.; Tam, C.S.; Barve, M.A.; Kuss, B.; Taylor, J.; Abdel-Wahab, O.; Schuster, S.J.; Palomba, M.L.; Lewis, K.L.; Roeker, L.E.; Davids, M.S.; Tan, X.N.; Fenske, T.S.; Wallin, J.; Tsai, D.E.; Ku, N.C.; Zhu, E.; Chen, J.; Yin, M.; Nair, B.; Ebata, K.; Marella, N.; Brown, J.R.; Wang, M. Pirtobrutinib in relapsed or refractory B-cell malignancies (BRUIN): A phase 1/2 study. Lancet, 2021, 397(10277), 892-901.
[http://dx.doi.org/10.1016/S0140-6736(21)00224-5] [PMID: 33676628]
[22]
Jiang, Z.; Qi, G.; Lu, W.; Wang, H.; Li, D.; Chen, W.; Ding, L.; Yang, X.; Yuan, H.; Zeng, Q. Omaveloxolone inhibits IL-1β-induced chondrocyte apoptosis through the Nrf2/ARE and NF-κB signalling pathways in vitro and attenuates osteoarthritis in vivo. Front. Pharmacol., 2022, 13, 952950.
[http://dx.doi.org/10.3389/fphar.2022.952950] [PMID: 36238561]
[23]
Probst, B.L.; Trevino, I.; McCauley, L.; Bumeister, R.; Dulubova, I.; Wigley, W.C.; Ferguson, D.A. RTA 408, A novel synthetic triterpenoid with broad anticancer and anti-inflammatory activity. PLoS One, 2015, 10(4), e0122942.
[http://dx.doi.org/10.1371/journal.pone.0122942] [PMID: 25897966]
[24]
Lee, A. Omaveloxolone: First approval. Drugs, 2023, 83(8), 725-729.
[http://dx.doi.org/10.1007/s40265-023-01874-9] [PMID: 37155124]
[25]
Ballesteros-Sánchez, A.; De-Hita-Cantalejo, C.; Sánchez-González, M.C.; Jansone-Langine, Z.; de Sotomayor, M.A.; Culig, J.; Sánchez-González, J.M. Perfluorohexyloctane in dry eye disease: A systematic review of its efficacy and safety as a novel therapeutic agent. Ocul. Surf., 2023, 30, 254-262.
[http://dx.doi.org/10.1016/j.jtos.2023.10.001] [PMID: 37813152]
[26]
Sheppard, J.D.; Evans, D.G.; Protzko, E.E. A review of the first anti-evaporative prescription treatment for dry eye disease: Perfluorohexyloctane ophthalmic solution. Am. J. Manag. Care, 2023, 29(14)(Suppl.), S251-S259.
[PMID: 37930231]
[27]
Steven, P.; Scherer, D.; Krösser, S.; Beckert, M.; Cursiefen, C.; Kaercher, T. Semifluorinated alkane eye drops for treatment of dry eye disease—a prospective, multicenter noninterventional study. J. Ocul. Pharmacol. Ther., 2015, 31(8), 498-503.
[http://dx.doi.org/10.1089/jop.2015.0048] [PMID: 26296040]
[28]
Tauber, J.; Wirta, D.L.; Sall, K.; Majmudar, P.A.; Willen, D.; Krösser, S. A randomized clinical study (SEECASE) to assess efficacy, safety, and tolerability of NOV03 for treatment of dry eye disease. Cornea, 2021, 40(9), 1132-1140.
[http://dx.doi.org/10.1097/ICO.0000000000002622] [PMID: 33369937]
[29]
Akinosoglou, K.; Schinas, G.; Gogos, C. Oral antiviral treatment for COVID-19: A comprehensive review on nirmatrelvir/ritonavir. Viruses, 2022, 14(11), 2540.
[http://dx.doi.org/10.3390/v14112540] [PMID: 36423149]
[30]
Heo, Y.A. Flotufolastat F 18: Diagnostic first approval. Mol. Diagn. Ther., 2023, 27(5), 631-636.
[http://dx.doi.org/10.1007/s40291-023-00665-y] [PMID: 37439946]
[31]
Kroenke, M.; Schweiger, L.; Horn, T.; Haller, B.; Schwamborn, K.; Wurzer, A.; Maurer, T.; Wester, H.J.; Eiber, M.; Rauscher, I. Validation of 18 F-rhPSMA-7 and 18 F-rhPSMA-7.3 PET imaging results with histopathology from salvage surgery in patients with biochemical recurrence of prostate cancer. J. Nucl. Med., 2022, 63(12), 1809-1814.
[http://dx.doi.org/10.2967/jnumed.121.263707] [PMID: 35393348]
[32]
Rufener, L.; Danelli, V.; Bertrand, D.; Sager, H. The novel isoxazoline ectoparasiticide lotilaner (Credelio™): A non-competitive antagonist specific to invertebrates γ-aminobutyric acid-gated chloride channels (GABACls). Parasit. Vectors, 2017, 10(1), 530.
[http://dx.doi.org/10.1186/s13071-017-2470-4] [PMID: 29089046]
[33]
Hoy, S.M. Motixafortide: First approval. Drugs, 2023, 83(17), 1635-1643.
[http://dx.doi.org/10.1007/s40265-023-01962-w] [PMID: 37996648]
[34]
Crees, Z.D.; Rettig, M.P.; Bashey, A.; Devine, S.M.; Jaglowski, S.; Wan, F.; Zhou, A.; Harding, M.; Vainstein-Haras, A.; Sorani, E.; Gliko-Kabir, I.; Grossman, B.J.; Westervelt, P.; DiPersio, J.F.; Uy, G.L. Hematopoietic stem cell mobilization for allogeneic stem cell transplantation by motixafortide, a novel CXCR4 inhibitor. Blood Adv., 2023, 7(18), 5210-5214.
[http://dx.doi.org/10.1182/bloodadvances.2023010407] [PMID: 37327120]
[35]
Bencardino, S.; D’Amico, F.; Faggiani, I.; Bernardi, F.; Allocca, M.; Furfaro, F.; Parigi, T.L.; Zilli, A.; Fiorino, G.; Peyrin-Biroulet, L.; Danese, S. Efficacy and safety of S1P1 receptor modulator drugs for patients with moderate-to-severe ulcerative colitis. J. Clin. Med., 2023, 12(15), 5014.
[http://dx.doi.org/10.3390/jcm12155014] [PMID: 37568417]
[36]
FDA Approved Drugs 2023. Available from: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=reportsSearch.process
[37]
Yun, M.R.; Kim, D.H.; Kim, S.Y.; Joo, H.S.; Lee, Y.W.; Choi, H.M.; Park, C.W.; Heo, S.G.; Kang, H.N.; Lee, S.S.; Schoenfeld, A.J.; Drilon, A.; Kang, S.G.; Shim, H.S.; Hong, M.H.; Cui, J.J.; Kim, H.R.; Cho, B.C. Repotrectinib exhibits potent antitumor activity in treatment-naïve and solvent-front–mutant ros1-rearranged non–small cell lung cancer. Clin. Cancer Res., 2020, 26(13), 3287-3295.
[http://dx.doi.org/10.1158/1078-0432.CCR-19-2777] [PMID: 32269053]
[38]
Gounder, M.; Ratan, R.; Alcindor, T.; Schöffski, P.; van der Graaf, W.T.; Wilky, B.A.; Riedel, R.F.; Lim, A.; Smith, L.M.; Moody, S.; Attia, S.; Chawla, S.; D’Amato, G.; Federman, N.; Merriam, P.; Van Tine, B.A.; Vincenzi, B.; Benson, C.; Bui, N.Q.; Chugh, R.; Tinoco, G.; Charlson, J.; Dileo, P.; Hartner, L.; Lapeire, L.; Mazzeo, F.; Palmerini, E.; Reichardt, P.; Stacchiotti, S.; Bailey, H.H.; Burgess, M.A.; Cote, G.M.; Davis, L.E.; Deshpande, H.; Gelderblom, H.; Grignani, G.; Loggers, E.; Philip, T.; Pressey, J.G.; Kummar, S.; Kasper, B. Nirogacestat, a γ-secretase inhibitor for desmoid tumors. N. Engl. J. Med., 2023, 388(10), 898-912.
[http://dx.doi.org/10.1056/NEJMoa2210140] [PMID: 36884323]
[39]
Shih, I.M.; Wang, T.L. Notch signaling, gamma-secretase inhibitors, and cancer therapy. Cancer Res., 2007, 67(5), 1879-1882.
[http://dx.doi.org/10.1158/0008-5472.CAN-06-3958] [PMID: 17332312]
[40]
ClinicalTrials.gov is a place to learn about clinical studies from around the world: 2023. https://www.clinicaltrials.gov/
[41]
Hao, X.; Bahia, R.K.; Cseh, O.; Bozek, D.A.; Blake, S.; Rinnenthal, J.; Weyer-Czernilofsky, U.; Rudolph, D.; Artee Luchman, H. BI-907828, a novel potent MDM2 inhibitor, inhibits glioblastoma brain tumor stem cells in vitro and prolongs survival in orthotopic xenograft mouse models. Neuro-oncol., 2023, 25(5), 913-926.
[http://dx.doi.org/10.1093/neuonc/noac271] [PMID: 36521007]
[42]
Wang, X.; Allen, S.; Blake, J.F.; Bowcut, V.; Briere, D.M.; Calinisan, A.; Dahlke, J.R.; Fell, J.B.; Fischer, J.P.; Gunn, R.J.; Hallin, J.; Laguer, J.; Lawson, J.D.; Medwid, J.; Newhouse, B.; Nguyen, P.; O’Leary, J.M.; Olson, P.; Pajk, S.; Rahbaek, L.; Rodriguez, M.; Smith, C.R.; Tang, T.P.; Thomas, N.C.; Vanderpool, D.; Vigers, G.P.; Christensen, J.G.; Marx, M.A. Identification of MRTX1133, a noncovalent, potent, and selective KRAS G12D inhibitor. J. Med. Chem., 2022, 65(4), 3123-3133.
[http://dx.doi.org/10.1021/acs.jmedchem.1c01688] [PMID: 34889605]
[43]
Hanan, E.J.; Braun, M.G.; Heald, R.A.; MacLeod, C.; Chan, C.; Clausen, S.; Edgar, K.A.; Eigenbrot, C.; Elliott, R.; Endres, N.; Friedman, L.S.; Gogol, E.; Gu, X.H.; Thibodeau, R.H.; Jackson, P.S.; Kiefer, J.R.; Knight, J.D.; Nannini, M.; Narukulla, R.; Pace, A.; Pang, J.; Purkey, H.E.; Salphati, L.; Sampath, D.; Schmidt, S.; Sideris, S.; Song, K.; Sujatha-Bhaskar, S.; Ultsch, M.; Wallweber, H.; Xin, J.; Yeap, S.; Young, A.; Zhong, Y.; Staben, S.T. Discovery of GDC-0077 (Inavolisib), a highly selective inhibitor and degrader of mutant PI3Kα. J. Med. Chem., 2022, 65(24), 16589-16621.
[http://dx.doi.org/10.1021/acs.jmedchem.2c01422] [PMID: 36455032]
[44]
Krystal, J.H.; Kane, J.M.; Correll, C.U.; Walling, D.P.; Leoni, M.; Duvvuri, S.; Patel, S.; Chang, I.; Iredale, P.; Frohlich, L.; Versavel, S.; Perry, P.; Sanchez, R.; Renger, J. Emraclidine, a novel positive allosteric modulator of cholinergic M4 receptors, for the treatment of schizophrenia: A two-part, randomised, double-blind, placebo-controlled, phase 1b trial. Lancet, 2022, 400(10369), 2210-2220.
[http://dx.doi.org/10.1016/S0140-6736(22)01990-0] [PMID: 36528376]
[45]
Fleischhacker, W.W.; Podhorna, J.; Gröschl, M.; Hake, S.; Zhao, Y.; Huang, S.; Keefe, R.S.E.; Desch, M.; Brenner, R.; Walling, D.P.; Mantero-Atienza, E.; Nakagome, K.; Pollentier, S. Efficacy and safety of the novel glycine transporter inhibitor BI 425809 once daily in patients with schizophrenia: A double-blind, randomised, placebo-controlled phase 2 study. Lancet Psychiatry, 2021, 8(3), 191-201.
[http://dx.doi.org/10.1016/S2215-0366(20)30513-7] [PMID: 33610228]

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