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Mini-Reviews in Medicinal Chemistry

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ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

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Mini-Review Article

Comprehensive Update on Synthetic Aspects of Bosentan Derivatives

Author(s): Jigar Panchal, Ashima Panchal, Sonika Jain*, Pankaj Kumar Jain, Jaya Dwivedi and Swapnil Sharma

Volume 23, Issue 12, 2023

Published on: 02 September, 2022

Page: [1238 - 1256] Pages: 19

DOI: 10.2174/1389557522666220510113702

Abstract

Bosentan and its analogues were first reported as endothelin (ET) receptor antagonists in US patent No. 5, 292,740 in 1994. Bosentan synthesis has been reported by employing different methods from the reaction between (4,6-dichloro-5-(2-methoxyphenoxy)-2,2'-bipyrimidine and 4- (tert-butyl) benzenesulfonamide and 4-(tert-butyl)-N-(6-chloro-5-(2-methoxyphenoxy)-[2,2'- bipyrimidin]-4-yl) benzenesulfonamide in the form of different salts like potassium salt, ammonium salt, sodium salt, and free, on its reaction with ethylene glycol. Several changes have been observed in the chemistry of the involved intermediate synthesis, particularly coupling chemistry, to produce bosentan derivatives with high purity and yield.

Keywords: Bosentan, endothelin, tracleer, antagonist, one-pot, catalysis.

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[1]
Li, X.; Liu, K.L.; Zheng, J.Q.; Chi, M.G.; Dong, J.J.; Dong, S.J.; Gong, Z.H. Pharmacological characterization of 3-azabicyclo[3,2,1] octane-1-yl-l-leucyl-d-tryptophanyl-d-4-Cl-phenylalanine: A novel ET(A) receptor-selective antagonist. Pulm. Pharmacol. Ther., 2008, 21(5), 780-787.
[http://dx.doi.org/10.1016/j.pupt.2008.06.001] [PMID: 18602014]
[2]
Gaitonde, A.; Manojkumar, B. Process for the introduction of hydroxyethoxy side chain in bosentan. U.S. Patent 20100249162A1, 2010.
[3]
Cai, J.; Liu, L.; Chen, J.; Cao, M.; Ji, M. Design, synthesis, and bioactivity of pyrazole acid derivatives as endothelin receptor antagonists. Med. Chem., 2013, 9(8), 1113-1122.
[http://dx.doi.org/10.2174/1573406411309080013] [PMID: 23521004]
[4]
Rubin, L.J.; Roux, S. Bosentan: A dual endothelin receptor antagonist. Expert Opin. Investig. Drugs, 2002, 11(7), 991-1002.
[http://dx.doi.org/10.1517/13543784.11.7.991] [PMID: 12084009]
[5]
Chen, J.; Luo, J.; Yang, X.; Luo, P.; Chen, Y.; Li, Z.; Li, J. Transition from Bosentan to Ambrisentan in pulmonary arterial hypertension: A single-center prospective study. Int. J. Gen. Med., 2021, 14, 2101-2107.
[http://dx.doi.org/10.2147/IJGM.S304992] [PMID: 34079351]
[6]
Castellví, I.; Simeón, C.P.; Sarmiento, M.; Casademont, J.; Corominas, H.; Fonollosa, V. Effect of bosentan in pulmonary hypertension development in systemic sclerosis patients with digital ulcers. PLoS One, 2020, 15(12), e0243651.
[http://dx.doi.org/10.1371/journal.pone.0243651] [PMID: 33301540]
[7]
Neidhart, W.; Breu, V.; Bur, D.; Hirth, G.; Muller, M.; Wessel, H.P.; Ramuz, H. The discovery of nonpeptide endothelin receptor antagonists. Progression towards Bosentan. Chimia (Aarau), 1996, 50(11), 529.
[8]
Verlinden, N.J.; Benza, R.L.; Raina, A. Safety and efficacy of transitioning from the combination of bosentan and sildenafil to alternative therapy in patients with pulmonary arterial hypertension. Pulm. Circ., 2020, 10(4), 2045894020945523.
[http://dx.doi.org/10.1177/2045894020945523] [PMID: 33354314]
[9]
Li, X.; Li, J.; Ma, X.; Chi, W.; Liu, H.; Hu, X.; Zheng, X.; Zhai, Z.; Li, J. Preparation method of therapeutic medicine for treating pulmonary arterial hypertension. C.N. Patent 104193687, 2017.
[10]
Neidhart, W.; Breu, V.; Bur, D.; Burri, K.; Clozel, M.; Hirth, G.; Klinkhammer, U.; Giller, T.; Ramuz, H. Discovery of Ro 48-5695: A potent mixed endothelin receptor antagonist optimized from bosentan. Bioorg. Med. Chem. Lett., 1997, 7(17), 2223-2228.
[http://dx.doi.org/10.1016/S0960-894X(97)00400-9]
[11]
Roux, S.; Breu, V.; Ertel, S.I.; Clozel, M. Endothelin antagonism with bosentan: A review of potential applications. J. Mol. Med. (Berl.), 1999, 77(4), 364-376.
[http://dx.doi.org/10.1007/s001090050363] [PMID: 10353441]
[12]
Rich, S.; McLaughlin, V.V. Endothelin receptor blockers in cardiovascular disease. Circulation, 2003, 108(18), 2184-2190.
[http://dx.doi.org/10.1161/01.CIR.0000094397.19932.78] [PMID: 14597580]
[13]
Clozel, M.; Breu, V.; Gray, G.A.; Kalina, B.; Löffler, B.M.; Burri, K.; Cassal, J.M.; Hirth, G.; Müller, M.; Neidhart, W. Pharmacological characterization of bosentan, a new potent orally active nonpeptide endothelin receptor antagonist. J. Pharmacol. Exp. Ther., 1994, 270(1), 228-235.
[PMID: 8035319]
[14]
Kompella, A.; Kasa, S.; Balina, V.S.; Kusumba, S.; Adibhatla, B.R.K.; Muddasani, P.R. Large scale process to prepare highly pure Bosentan monohydrate. Sci. J. Chem., 2014, 2(6-1), 9-15.
[15]
Dimitar, S.; Latimer, K.; Petrovsky, N. Dyspnea in Pulmonary Arterial Hypertension; INTECH Open Access Publisher: London, 2011, pp. 191-208.
[16]
Burri, K.; Clozel, M.; Fischli, W.; Hirth, G.; Loffler, B.; Neidhart, W.; Ramuz, H. Sulfonamides. U.S. Patent 5292740, 1994.
[17]
Harrington, P.J.; Khatri, H.N.; Dehoff, B.S. Preparation of sulphonamide. U.S. Patent 6136971, 2000.
[18]
Harrington, P.J.; Khatri, H.N.; DeHoff, B.S.; Guinn, M.R.; Boehler, M.A.; Glaser, K.A. Research and development of a second-generation process for bosentan, an endothelin receptor antagonist. Org. Process Res. Dev., 2002, 6(2), 120-124.
[http://dx.doi.org/10.1021/op010234i]
[19]
Ganem, B.; Small, V.R., Jr Ferric chloride in acetic anhydide. Mild and versatile reagent for the cleavage of ethers. J. Org. Chem., 1974, 39(25), 3728-3730.
[http://dx.doi.org/10.1021/jo00939a026]
[20]
Schlessinger, R.H.; Nugent, R.A. Total synthesis of racemic verrucarol. J. Am. Chem. Soc., 1982, 104(4), 1116-1118.
[http://dx.doi.org/10.1021/ja00368a044]
[21]
Jung, M.E.; Lyster, M.A. Quantitative dealkylation of alkyl ethers via treatment with trimethylsilyl iodide. A new method for ether hydrolysis. J. Org. Chem., 1977, 42(23), 3761-3764.
[http://dx.doi.org/10.1021/jo00443a033]
[22]
Eder, U.; Haffer, G.; Neef, G.; Sauer, G.; Seeger, A.; Wiechert, R. Total synthesis of natural and non-natural steroid hormones. Chem. Ber., 1977, 110, 3161.
[http://dx.doi.org/10.1002/cber.19771100921]
[23]
Halpern, B.; Mitecki, D.E. The deblocking of t-butyloxycarbonyl-peptides with formic acid. Tetrahedron Lett., 1967, 31(31), 3031-3033.
[http://dx.doi.org/10.1016/S0040-4039(00)90909-2] [PMID: 6046348]
[24]
Niphade, N.C.; Jagtap, K.M.; Gaikawad, C.T.; Jachak, M.N.; Mathad, V.T. Facile one-pot process for large-scale production of highly pure bosentan monohydrate, an endothelin receptor antagonist. Org. Process Res. Dev., 2011, 15(6), 1382-1387.
[http://dx.doi.org/10.1021/op200197z]
[25]
Joshi, S. Process for preparation of endothelial receptor antagonist (bosentan). U.S. Patent 20120136015A1, 2012.
[26]
Manne, S.R.; Srinivasan, T.R.; Sajja, E.; Rebelli, P.; Nadendla, H.K.; Bairy, K.R.; Chepyala, K.R. Improved procedure for the preparation of bosentan, an endothelin receptor antagonist. Org. Prep. Proced. Int., 2013, 45(6), 510-514.
[http://dx.doi.org/10.1080/00304948.2013.835222]
[27]
Manne, S. R.; Sajja, E.; Ghojala, V. R. Improved and novel process for the preparation of bosentan. W.O. Patent 2009095933A2, 2009.
[28]
Lee, C.R.; Lee, S.Y.; Nam, T.G. Succinct synthesis of bosentan utilizing glycol Mono-THP ether. Synth. Commun., 2014, 44(17), 2488-2493.
[http://dx.doi.org/10.1080/00397911.2014.904881]
[29]
Pradeep, R.; Rao, Y.J.; Bharathi, Y.K.; Subbanarsimulu, P.; Reddy, G.V.; Reddy, B.K. An alternate synthesis of bosentan monohydrate, an endothelin receptor antagonist. Synlett, 2014, 25(02), 265-269.
[30]
Rebelli, P.; Yerrabelly, J.R.; Yalamanchili, B.K.; Kommera, R.; Ghojala, V.R.; Bairy, K.R. A new efficient synthetic process for an endothelin receptor antagonist, bosentan monohydrate. Org. Process Res. Dev., 2013, 17(8), 1021-1026.
[http://dx.doi.org/10.1021/op400100s]
[31]
Sergio, R.R.; Clotet, J.J. Process for the preparation of bosentan. W.O. Patent 2010012637A1, 2010.
[32]
Burri, K.; Clozel, M.; Fischli, W.; Hirth, G.; Ramuz, H. Preparation of pyrimidinylaryl sulfonamides and analogs for treatment of circulatory disorders. CA Patent 2071193A1, 1992.
[33]
Sergio, R.R.; Clotet, J.H. Process for preparation of bosentan. W.O. Patent 2011117143A1, 2011.
[34]
Morimoto, H.; Shimadzu, H.; Hosaka, T.; Kawase, Y.; Yasuda, K.; Kikkawa, K.; Yamauchi-Kohno, R.; Yamada, K. Modifications and structure-activity relationships at the 2-position of 4-sulfonamidopyrimidine derivatives as potent endothelin antagonists. Bioorg. Med. Chem. Lett., 2002, 12(1), 81-84.
[http://dx.doi.org/10.1016/S0960-894X(01)00682-5] [PMID: 11738578]
[35]
Vedejs, E.; Chapman, R.W.; Fields, S.C.; Lin, S.; Schrimpf, M.R. Conversion of arylboronic acids into potassium aryltrifluoroborates: Convenient precursors of arylboron difluoride Lewis acids. J. Org. Chem., 1995, 60(10), 3020-3027.
[http://dx.doi.org/10.1021/jo00115a016]
[36]
Gros, P.C. Other stoichiometric metalation reactions on pyrimidine and quinazoline. W.O. Patent 2007058602 A2, 2012.
[http://dx.doi.org/10.1007/7081_2012_93]
[37]
Sinha, B.K.; Raju, K.R.; Reddy, B.S.; Rangarao, V.P. An improved process for the preparation of Bosentan. W.O. Patent 2010024056 2011, 2010.
[38]
Modi, R.I.; Gudaparthi, O.; Chowdhary, A.S. Process for the preparation of bosentan. W.O. Patent 2013186706, 2013.
[39]
Kishan, K.A.; Srinivasu, K.; Swamy, B.V.; Subhash, K. Process for the preparation of bosentan monohydrate. W.O. Patent 2013136110, 2013.
[40]
Raju, K.R.; Reddy, B.S.; Somannavar, Y.S.; Sinha, B.K.; Babu, P.K.; Raju, K.M. Improved large-scale synthesis of bosentan monohydrate. Org. Prep. Proced. Int., 2016, 48(6), 481-491.
[http://dx.doi.org/10.1080/00304948.2016.1234826]
[41]
Sata, K; Pandey, B. A process for the preparation of bosentan. E.P. Patent 23315623A1, 2009.
[42]
Duffey, S.S.; Aldrich, J.R.; Blum, M.S. Biosynthesis of phenol and guaiacol by the hemipteran Leptoglossus phyllopus. Comp. Biochem. Physiol. B, 1977, 56(2), 101-102.
[http://dx.doi.org/10.1016/0305-0491(77)90029-3] [PMID: 830476]
[43]
Vinayak, G. A process for the preparation of bosentan. W.O. Patent 2012056468A1, 2011.
[44]
Garcia, G. E. Process for the preparation of endothelin receptor antagonists. W.O. Patent 2010015623A1, 2010.
[45]
Rebelli, P.; Yerrabelly, J.R.; Kommera, R.; Ghojala, V.R.; Bairy, K.R. New approaches to endothelin receptor antagonist-bosentan. Lett. Org. Chem., 2013, 10(5), 364-368.
[http://dx.doi.org/10.2174/1570178611310050011]

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