Quinoline-Based FDA-Approved Drugs: Synthetic Route and Clinical Uses

Abstract

In the last 25 years, the U.S. Food and Drug Administration (FDA) approved 11 new molecular entities (NMEs) comprising quinoline as core moiety. These drugs are primarily used for the treatment of anemia, malaria, hepatitis, and various types of cancer, i.e., lung, breast, kidney, blood, and thyroid. Based on their approval date, a chronological discussion on these marketed drugs is provided. This Perspective summarizes the industrial synthesis, mechanism of action, and clinical uses of the quinoline-based FDA-approved NMEs of the 21st century.

1 Introduction

2 Quinoline-Based FDA-Approved Drugs

2.1 Mitapivat (2022)

2.2 Tivozanib (2021)

2.3 Capmatinib (2020)

2.4 Tafenoquine (2018)

2.5 Neratinib (2017)

2.6 Lenvatinib (2015)

2.7 Simeprevir (2013)

2.8 Bosutinib (2012)

2.9 Cabozantinib (2012)

2.10 Bedaquiline (2012)

2.11 Pitavastatin (2009)

3 Conclusion

4 Abbreviations

Key words

drugs - FDA - NMEs - quinoline

Publikationsverlauf

Eingereicht: 22. Januar 2025

Angenommen nach Revision: 21. März 2025

Accepted Manuscript online:
21. März 2025

Artikel online veröffentlicht:
20. Mai 2025

• References

• 1a Rajni V, Singh L, Rana R, Bendi A. ChemistrySelect 2022; 7: e202203648
• 1b Manske RH. Chem. Rev. 1942; 30: 113
• 2a Achan J, Talisuna AO, Erhart A, Yeka A, Tibenderana JK, Baliraine FN, D’Alessandro U. Malar. J. 2011; 10: 144
• 2b Roth K, Streller S. ChemViews Magazine 2013, 7.
• 3 Cortegiani A, Ingoglia G, Ippolito M, Giarratano A, Einav S. J. Crit. Care 2020; 57: 279
• 4 Ahmad SS, Rahi M, Ranjan V, Sharma A. Int. J. Parasitol. Drugs Drug Resist. 2021; 17: 23
• 5a Pelletier PJ, Caventou JB. Ann. Chim. Phys. 1820; 15: 291
• 5b Pelletier PJ, Caventou JB. Ann. Chim. Phys. 1820; 15: 337
• 5c Pelletier PJ, Caventou JB. Analyse Chimique des Quinquina 1821
• 6 Strecker A. Justus Liebigs Ann. Chem. 1854; 91: 155
• 7a Rabe P. Justus Liebigs Ann. Chem. 1909; 365: 353
• 7b Rabe P. Ber. Dtsch. Chem. Ges. 1908; 41: 62
• 8 Woodward RB, Wendler NL, Brutschy FJ. J. Am. Chem. Soc. 1945; 67: 1425
• 9 Proštenik M, Prelog V. Helv. Chim. Acta 1943; 26: 1965
• 10 Gutzwiller J, Uskoković MR. Helv. Chim. Acta 1973; 56: 1494
• 11 Kaufman TS, Rúveda EA. Angew. Chem. Int. Ed. 2005; 44: 854
• 12a Foley M, Tilley L. Int. J. Parasitol. 1997; 27: 231
• 12b Senerovic L, Opsenica D, Moric I, Aleksic I, Spasić M, Vasiljevic B. Adv. Exp. Med. Biol. 2020; 1282: 37
• 12c Matada BS, Pattanashettar R, Yernale NG. Bioorg. Med. Chem. 2021; 32: 115973
• 13 Devaux CA, Rolain JM, Colson P, Raoult D. Int. J. Antimicrob. Agents 2020; 55: 105938
• 14 Manivannan E, Karthikeyan C, Moorthy NH. N, Chaturvedi SC. Front. Pharmacol. 2021; 12: 584940
• 15 Geleris J, Sun Y, Platt J, Zucker J, Baldwin M, Hripcsak G, Schluger NW. N. Eng. J. Med. 2020; 382: 2411
• 16a Hernandez AV, Roman YM, Pasupuleti V, Barboza JJ, White CM. Ann. Intern. Med. 2020; 173: 287
• 16b Letter of Authorization (accessed: March 28, 2020): https://www.fda.gov/media/136534/download
• 17 https://www.fda.gov/media/138945/download (accessed March 10, 2025)
• 18 Pratibha Y, Shah K. Bioorg. Chem. 2021; 109: 104639
• 19a https://clinicaltrials.gov/study/NCT00080015 (accessed date March 10, 2025)
• 19b Joshi AA, Viswanathan CL. Anti-infect. Agents Med. Chem. 2006; 105
• 19c Wise-Draper TM, Moorthy G, Salkeni MA, Karim NA, Thomas HE, Mercer CA, Beg MS, O’Gara S, Olowokure O, Fathallah H, Kozma SC, Thomas G, Rixe O, Desai P, Morris JC. Target. Oncol. 2017; 12: 323
• 19d To KK, Poon DC, Wei Y, Wang F, Lin G, Fu L. Br. J. Pharmacol. 2015; 172: 4089
• 19e Kim W, Tripathi M, Kim C, Vardhineni S, Cha Y, Kandi SK, Feitosa M, Kholiya R, Sah E, Thakur A, Kim Y, Cohen B, Rawat DS, Kim K. Nat. Commun. 2023; 14: 4283
• 20 https://www.researchnester.com/reports/quinoline-market/4995 (accessed Dec. 5, 2024)
• 21a Brown DG. J. Med. Chem. 2024; 67: 1690
• 21b Marshall CM, Federice JG, Bell CN, Cox PB, Njardarson JT. J. Med. Chem. 2024; 64: 23391
• 21c Bhutani P, Joshi G, Raja N, Bachhav N, Rajanna PK, Bhutani H, Paul AT, Kumar R. J. Med. Chem. 2021; 64: 2312
• 21d Brown DG, Wobst HJ. J. Med. Chem. 2021; 64: 2312
• 22a Dhiman AK, Thakur A, Kumar R, Sharma U. Asian J. Org. Chem. 2020; 9: 1502
• 22b Chandra D, Dhiman AK, Kumar R, Sharma U. Eur. J. Org. Chem. 2019; 2753
• 22c Gupta SS, Parmar D, Kumar R, Chandra D, Sharma U. Catal. Rev. 2024; 66: 713
• 22d Sharma U, Kumar R, Gupta SS, Chandra D. Quinolines . In Science of Synthesis . Georg Thieme Verlag; Stuttgart: 2022. Steven Diver, Timothy J. Donohoe , John A. Joule. DOI:
• 22e Kumar R, Thakur A. Sachin Chandra D, Kumar Dhiman A, Kumar Verma P, Sharma U. Coord. Chem. Rev. 2024; 499: 215453
• 23a Pilo F, Angelucci E. Drugs Today 2023; 59: 125
• 23b Zhuang-Yan A, Shirley M. Drugs 2023; 83: 1613
• 24 Mazurek S. Int. J. Biochem. Cell Biol. 2011; 43: 969
• 25 Ji D, Peng Y, Zhang Y, Tang X, Zhao M, Ran L, Liu Y. Heliyon 2024; 10: e36507
• 26 Zhang JY, Wang YT, Sun L, Wang SQ, Chen ZS. Mol. Biomed. 2023; 4: 26
• 27 Salituro FG, Saunders JO, Yan S. US 20100331307A1, 2010
• 28 Sizemore J, Guo L, Mirmehrabi M, Su Y. WO 2019104134A1, 2019
• 29 Goura R, Manabolu Surya SB, Katari NK, Achampeta Kodanda R, Rebelly P, Chakilam N. Org. Process. Res. Dev. 2024; 28: 4024
• 30a Kim ES. Drugs 2017; 77: 1917
• 30b Santoni M, Massari F, Piva F, Carrozza F, Di Nunno V, Cimadamore A, Martignetti A, Montironi R, Battelli N. Expert Opin. Pharmacother. 2018; 19: 1021
• 30c Fogli S, Porta C, Del Re M, Crucitta S, Gianfilippo G, Danesi R, Rini BI, Schmidinger M. Cancer Treat. Rev. 2020; 84: 101966
• 31a Bronte E, Galvano A, Novo G, Russo A. Cardio-Oncology: Principles, Prevention and Management . Gottlieb RA, Mehta PK. Academic Press; London: 2016: 69
• 31b Caquelin L, Gewily M, Mottais W, Tebaldi C, Laviolle B, Naudet F, Locher C. BMC Cancer 2022; 22: 381
• 32a Tamatam R, Mohammed A. Eur. J. Med. Chem. 2024; 272: 116441
• 32b Liu M, Hu L, Wang X, Zhu H. Adv. Mater. Res. 2012; 396: 396
• 32c Kubo K, Sakai T, Nagao R, Fujiwara Y, Isoe T, Hasegawa K. US 6821987B2, 2004
• 33 Wolf J, Seto T, Han J.-Y, Reguart N, Garon EB, Groen HJ. M, Tan DS. W, Hida T, de Jonge M, Orlov SV, Smit EF, Souquet P.-J, Vansteenkiste J, Hochmair M, Felip E, Nishio M, Thomas M, Ohashi K, Toyozawa R, Overbeck TR, de Marinis F, Kim T.-M, Laack E, Robeva A, Le Mouhaer S, Waldron-Lynch M, Sankaran B, Balbin OA, Cui X, Giovannini M, Akimov M, Heist RS. N. Engl. J. Med. 2020; 383: 944
• 34a Kim S, Kim TM, Kim D.-W, Kim S, Kim M, Ahn Y.-O, Keam B, Heo DS. Cancer Res. Treat. 2019; 51: 951
• 34b Mathieu LN, Larkins E, Akinboro O, Roy P, Amatya AK, Fiero MH, Mishra-Kalyani PS, Helms WS, Myers CE, Skinner AM, Aungst S, Jin R, Zhao H, Xia H, Fourie ZirkelbachJ, Bi Y, Li Y, Liu J, Grimstein M, Zhang X, Woods S, Reece K, Abukhdeir AM, Ghosh S, Philip R, Tang S, Goldberg KB, Pazdur R, Beaver JA, Singh H. Clin. Cancer Res. 2022; 28: 249
• 35 Hughes DL. Org. Process Res. Dev. 2021; 25: 2192
• 36a Zhou J, Xu M, He C, Zhang C, Qian D.-Q, Metcalf B, Yao W. US 7767675B2, 2010
• 36b Weng L, Qiao L, Zhou J, Liu P, Pan Y. US 8420645B2, 2013
• 36c Weng L, Qiao L, Zhou J, Liu P, Pan Y. US 20090291956A1, 2009
• 37 Frampton JE. Drugs 2018; 78: 1517
• 38 Lu KY, Derbyshire ER. Biochemistry 2020; 59: 911
• 39 de Villiers KA, Egan TJ. Acc. Chem. Res. 2021; 54: 2649
• 40a Baird JK. Clin. Microbiol. Rev. 2019; 32: 10
• 40b Dow G, Smith B. Malaria J. 2017; 16: 209
• 40c Flannery EL, Fidock DA, Winzeler EA. J. Med. Chem. 2013; 56: 7761
• 41 Lamontagne MP, Blumbergs P, Smith DC. J. Med. Chem. 1989; 32: 1728
• 42a Ugwuegbulam CO, Foy JE. WO 1997013753A1, 1997
• 42b Zhu W, Wang J, Wang S, Gu Z, Aceña JL, Izawa K, Liu H, Soloshonok VA. J. Fluor. Chem. 2014; 167: 37
• 43 Kavthe RD, Kincaid JR. A, Lipshutz BH. ACS Sustainable Chem. Eng. 2022; 10: 16896
• 44 Tiwari SR, Mishra P, Abraham J. Clin. Breast Cancer 2016; 16: 344
• 45 Xuhong JC, Qi XW, Zhang Y, Jiang J. Am. J. Cancer Res. 2019; 9: 2103
• 46 Cosgrove D, Piscaglia F, Bamber J, Bojunga J, Correas JM, Gilja OA, Klauser AS, Sporea I, Calliada F, Cantisani V, D’Onofrio M, Drakonaki EE, Fink M, Friedrich-Rust M, Fromageau J, Havre RF, Jenssen C, Ohlinger R, Săftoiu A, Schaefer F, Dietrich CF. Ultraschall Med 2013; 34: 238
• 47a Tsou HR, Mamuya N, Johnson BD, Reich MF, Gruber BC, Ye F, Wissner A. J. Med. Chem. 2001; 44: 2719
• 47b Wissner A, Overbeek E, Reich MF, Floyd MB, Johnson BD, Mamuya N, Rosfjord EC, Discafani C, Davis R, Shi X, Rabindran SK. J. Med. Chem. 2003; 46: 49
• 48 Tsou HR, Overbeek-Klumpers EG, Hallett WA, Reich MF, Floyd MB, Johnson BD, Michalak RS, Nilakantan R, Discafani C, Golas J, Rabindran SK, Shen R, Shi X, Wang YF, Upeslacis J, Wissner A. J. Med. Chem. 2005; 48: 1107
• 49 Chew W, Cheal GK, Lunetta JF. WO 2006127207A1, 2006
• 50 Motzer RJ, Taylor MH, Evans TR. J, Okusaka T, Glen H, Lubiniecki GM, Dutcus C, Smith AD, Okpara CE, Hussein Z, Hayato S, Tamai T, Makker V. Expert Rev. Anticancer Ther. 2022; 22: 383
• 51 Cabanillas ME, Habra MA. Cancer Treat. Rev. 2016; 42: 47
• 52a Funahashi Y, Tsuruoka A, Matsukura M, Haneda T, Fukuda Y, Kamata J, Takahashi K, Matsushima T, Miyazaki K, Nomoto K.-I, Watanabe T, Obaishi H, Yamaguchi A, Suzuki S, Nakamura K, Mimura F, Yamamoto Y, Matsui J, Matsui K, Yoshiba T, Suzuki Y, Arimoto I. US 20040053908A1, 2004
• 52b Liang X, Yang Q, Wu P, He C, Yin L, Xu F, Yin Z, Yue G, Zou Y, Li L, Song X, Lv C, Zhang W, Jing B. Bioorg. Chem. 2021; 113: 105011
• 53a Kubo K, Sakai T, Nagao R, Fujiwara Y, Isoe T, Hasegawa K. US 7612208B2, 2004
• 53b Sakaguchi T, Tsuruoka A. US 20070004773A1, 2007
• 54 Zhu Y, Zhang X, Liu F, Gu H, Tang J, Zhu B, Tang S, Wang L. CN 105985289A, 2016
• 55 Sadineni RK, Rapolu RK, Raju VV. N. K. V. P, Srinivasu N, Malladi S, Mulakayala N. Chem. Pap. 2021; 75: 1475
• 56 Izquierdo L, Helle F, François C, Castelain S, Duverlie G, Brochot E. Pharmgenomics Pers. Med. 2014; 75: 241
• 57a Sauberan JB, Neely MN, Bradley JS. Principles and Practice of Pediatric Infectious Diseases. Long SS, Prober CG, Fischer M, Kimberlin D. Elsevier; Amsterdam: 2018: 1551
• 57b Lawitz E, Sulkowski MS, Ghalib R, Rodriguez-Torres M, Younossi ZM, Corregidor A, DeJesus E, Pearlman B, Rabinovitz M, Gitlin N, Lim JK, Pockros PJ, Scott JD, Fevery B, Lambrecht T, Ouwerkerk-Mahadevan S, Callewaert K, Symonds WT, Picchio G, Lindsay KL, Beumont M, Jacobson IM. Lancet 2014; 384: 1756
• 58a Horvath A, Wuyts S, Depre DP. M, Couck Wouter LJ, Cuypers JL. J, Harutyunyan S, Binot GF. S.
• 58b Ormerod DJ, Depre DP. M, Horvath A. WO 2011113859A1, 2011
• 58c Horvath A, Ormerod DJ, Depre DP. M, Cerpentier V. WO 2010072742A1, 2010
• 58d Horvath A, Depre DP. M, Ormerod DJ. WO 2008092955A1, 2008
• 59 Kantarjian HM, Jabbour EJ, Lipton JH, Castagnetti F, Brümmendorf TH. Clin. Lymphoma Myeloma Leuk. 2024; 24: 285
• 60 Breccia M, Binotto G. Rare Cancers Ther. 2015; 3: 35
• 61a Boschelli DH, Wang YD, Johnson SL, Berger DM. US 20030212276A1, 2003
• 61b Boschelli DH, Zaleska MM, Boschelli FC, Arndt KT. WO 2004075898A1, 2004
• 62 Mao Y, Zhu C, Kong Z, Wang J, Zhu G, Ren X. Synthesis 2015; 47: 3133
• 63 Maroto P, Porta C, Capdevila J, Apolo AB, Viteri S, Rodriguez-Antona C, Martin L, Castellano D. Ther. Adv. Med. Oncol. 2022; 14
• 64 Yakes FM, Chen J, Tan J, Yamaguchi K, Shi Y, Yu P, Joly AH. Mol. Cancer Ther. 2011; 10: 2298
• 65 Bentzien F, Zuzow M, Heald N, Gibson A, Shi Y, Goon L, Yakes FM. Thyroid 2013; 23: 1569
• 66a Joshi A, Sahu A, Noronha V, Patil V, Prabhash K. Indian J. Surg. Oncol. 2018; 9: 97
• 66b Osanto S, van der Hulle T. Ther. Adv. Urol. 2018; 10: 109
• 67 Fang R, Wang B, Zhao Z, Yin L, Wang H, Xu JA. Org. Prep. Proced. Int. 2019; 51: 381
• 68 Sarathy JP, Gruber G, Dick T. Antibiotics 2019; 8: 261
• 69 Deshkar AT, Shirure PA. Cureus 2022; 14: e28519
• 70a Calvert MB, Furkert DP, Cooper CB, Brimble MA. Bioorg. Med. Chem. Lett. 2020; 12: 127172
• 70b Van Gestel JF. E, Guillemont JE. G, Venet MG, Pignet HJ. J, Decrane LF. B, Vernier DF. J. WO 2004011436A1, 2004
• 70c Andries K, Verhasselt P, Guillemont J, Göhlmann HW. H, Neefs J.-M, Winkler H, Van Gestel J, Timmerman P, Zhu M, Lee E, Williams P, de Chaffoy D, Huitric E, Hoffner S, Cambau E, Truffot-Pernot C, Lounis N, Jarlier V. Science 2005; 307: 223
• 71a Porstmann FR, Horns S, Bader T. CA 2606675C, 2013
• 71b Hegyi JF. A. L, Aelterman WA. A, Lang YL, Stokbroekx SC. M, Leys C, Van Remoortere PJ. M, Faure A. US 8546428B2, 2013
• 72a Saga Y, Motoki R, Makino S, Shimizu Y, Kanai M, Shibasaki M. J. Am. Chem. Soc. 2010; 132: 7905
• 72b Chandrasekhar S, Babu GK, Mohapatra DK. Eur. J. Org. Chem. 2011; 2057
• 73 Mukhtar RY. A, Reid J, Reckless JP. D. Int.J.Clin.Pract. 2005; 59: 239
• 74 Schachter M. Fundam. Clin. Pharmacol. 2005; 19: 117
• 75 Tripathi KD. Essentials of Medical Pharmacology, 7th ed. Jaypee Brothers; New Delhi/London/Panama: 2017: 636
• 76a Taylor S, Adhikari R. Biol. Res. Nurs. 2025; 27: 71
• 76b Reilly T, King G, Park JH, Tracy A. Drug Forecast 2010; 35: 204
• 77 Van der Schaaf PA, Blatter F, Szelagiewicz M, Schoening K.-U. EP 2500339A1, 2012
• 78 Dwivedi SD, Patel DJ, Shah AP, Khera B. WO 2012025939A1, 2012
• 79 Miyachi N, Yanagawa Y, Iwasaki H, Ohara Y, Hiyama T. Tetrahedron Lett. 1993; 34: 1993