- Discovery and development of an efficient process to atovaquone
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The discovery and development of an efficient and more sustainable manufacturing route to the antipneumocystic agent atovaquone (2-((1R,4R)-4-(4-chlorophenyl)cyclohexyl)-3-hydroxynaphthalene-1,4-dione) 1 is described. The existing commercial route to atovaquone delivers a poor yield of product and uses expensive reagents. The new synthesis commences with readily available phthalic anhydride, which is converted to 1,4-isochromandione 5 and then to atovaquone 1 by reaction with 4-(4-chlorophenyl)cyclohexanecarboxylic acid 3 using key bromination, Rosenmund reduction, and rearrangement chemistries. Downstream processing to atovaquone is both high yielding and robust, and the resulting process has been demonstrated on 200-kg scale. The process is simple, uses cheap raw materials, and is more sustainable in that it avoids lowyielding silver-promoted chemistry and isomerisation procedures. It includes a robust, facile, and highly efficient procedure to 1,4-isochromandione 5, and routes to 4-(4-chlorophenyl)cyclohexanecarboxaldehyde 9 have also been developed, including a Rosenmund method that was demonstrated on pilot-plant scale. Also discussed are the route-derived impurities and processing amendments to control their formation.
- Britton, Hugh,Catterick, David,Dwyer, Andrew N.,Gordon, Andrew H.,Leach, Stuart G.,McCormick, Chris,Mountain, Clive E.,Simpson, Alec,Stevens, David R.,Urquhart, Michael W. J.,Wade, Charles E.,Warren, John,Wooster, Nick F.,Zilliox, Audrey
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p. 1607 - 1617
(2013/02/23)
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- PROCESS FOR THE EPIMERIZATION OF ATOVAQUONE ISOMER, ATOVAQUONE INTERMEDIATES AND MIXTURE THEREOF
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Provided is a process for the epimerization of the cis isomer of atovaquone, atovaquone intermediates and isomeric mixtures thereof into their corresponding trans-isomers resulting in higher yield of pure atovaquone.
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Page/Page column 5
(2011/06/26)
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- PROCESS FOR PREPARATION OF ATOVAQUONE AND THE CONVERSION OF CIS-ISOMER TO TRANS- ISOMER
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Substantially pure atovaquone and parocess for the preparation thereof is disclosed.
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Page/Page column 11; 12
(2008/12/04)
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- Synthesis of atovaquone
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A short synthesis of atovaquone I is achieved via the radical coupling of the trans-1,4-substituted cyclohexyl mono-oxalate 2 and 2- chloronapthoquinone under phase transfer conditions.
- Williams, David R.,Clark, Michael P.
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p. 7629 - 7632
(2007/10/03)
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- Method for treating animals infected with Babesia spp.
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The present invention relates to pharmaceutical compositions for the treatment and/or prophylaxis of protozoal infections caused by Kinetoplastida, Apicomplexa, Anaerobic protozoa and Mircosporidia comprising 2-[4-(4-chlorophenyl)cyclohexyl]-3-hydroxy-1,4-naphthoquinone or a physiologically acceptable salt or other functional derivative thereof as active ingredient and to a method of treating or preventing siad protozoal infections in an animal which comprises administering to said animal an effective amount of siad compound.
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- Use of 2-(4-(4-chlorophenyl)cyclohexyl)-3-hydroxy-1,4-Naphthoquinone for the treatment of cancer
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The present invention relates to the use of 2-[4-(4-chlorophenyl)cyclohexyl]-3-hydroxy-1,4-naphthoquinone or a physiologically acceptable salt or other physiologically functional derivative thereof for the manufacture of a medicament for the treatment of tumours in animals, to pharmaceutical compositions for the treatment of tumours in animals, to pharmaceutical compositions for the treatment of tumours, comprising said compound as active ingredient and to a method of treating tumours in an animal which comprises administering to said animal an effective amount of said compound.
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- Medicaments for the treatment of toxoplasmosis
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The present invention relates to the use of 2-[4-(4-chlorophenyl) cyclohexyl]-3-hydroxy-1,4-naphthoquinone or a physiologically acceptable salt or other physiologically funtional derivative thereof for the manufacture of a medicament for the treatment and/or prophylaxis of toxoplasmosis in animals, to pharmaceutical compositions for the treatment and/or prophylaxis of toxoplasmosis, comprising said compound as active ingredient and to a method of treating or preventing toxoplasmosis in an animal which comprises administering to said animal an effective amount of said compound.
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