Initial synthesis of UK-427,857 (Maraviroc)
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Acknowledgements
The authors wish to thank Andy Fowler for supplying and recommending the polymer supported reagent and Torren Peakman for his assistance with analysis of the 1H spectra.
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2016, TetrahedronCitation Excerpt :Maraviroc, originally designed UK-427857, was developed by the drug company Pfizer and was approved by the FDA in 2007 (Fig 9). Price et al.78 reported the preparation of Maraviroc 9 (Scheme 70). The starting material was the commercially available chirally pure β-amino ester which was protected in high yield.
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2015, Tetrahedron LettersCitation Excerpt :The molecular structure of maraviroc also induced diverse and creative efforts to construct its single, nitrogen-bearing benzylic stereocenter. The pioneering and highly convergent medicinal chemistry9 and process chemistry10,11 syntheses of maraviroc (2) by Pfizer (Scheme 1) utilized an intermolecular Mannich/enantiomer resolution process to produce β-amino ester 4, a key intermediate that was subsequently employed in coupling reactions with 4,4-difluorocyclohexane-1-carboxylic acid 5 and tropane triazole 612 to complete the synthesis. The subsequent syntheses of maraviroc by the laboratories of Schaus13 and Córdova14 retained the logic of Pfizer’s convergent synthesis design and featured chiral catalyst-controlled, asymmetric allylation and aza-Michael reactions, respectively, to establish the absolute configuration of the nitrogen-bearing stereocenter of maraviroc (2).
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2013, Annual Reports in Medicinal ChemistryCitation Excerpt :Although several compounds almost made it, none progressed into the clinic, although one was tested successfully as a topical agent in primate models using a vaginal application. The concept was finally realized by Pfizer23 who were able to commercialize SELZENTRY® (maraviroc) as a CCR5 receptor antagonist for the treatment of HIV. Returning to the nucleoside area, my work switched to focus on inhibitors of hepatitis C RNA-dependent RNA polymerase, again with virology colleagues at Merck West Point (Daria Hazuda, Dave Olsen, and Steve Carroll) and collaborators at Isis Pharmaceuticals.