(1R,21S,24S)-21-tert-butyl-N-((1R,2R)-1-{[(cyclopropylsulfonyl)amino]carbonyl}-2-ethylcyclopropyl)-16,16-dimethyl-3,19,22-trioxo-2,18-dioxa-4,20,23-triazatetracyclo[21.2.1.14,7.06,11]-heptacosa-6,8,10-triene-24-carboxamide
923590-37-8 cas no
vaniprevir (MK-7009) is a macrocyclic hepatitis C virus NS3/4a protease inhibitor, is active against both the genotype 1 and genotype 2 NS3/4a protease enzymes. vaniprevir (MK-7009) has good plasma exposure and excellent liver exposure in multiple species.
Vaniprevir (MK-7009) is a macrocyclic Hepatitis C virus (HCV) NS3/4a protease inhibitor, developed by Merck & Co., which is currently in clinical testing.[1]
- McCauley JA, McIntyre CJ, Rudd MT, Nguyen KT, Romano JJ, Butcher JW, Gilbert KF, Bush KJ, Holloway MK, Swestock J, Wan BL, Carroll SS, DiMuzio JM, Graham DJ, Ludmerer SW, Mao SS, Stahlhut MW, Fandozzi CM, Trainor N, Olsen DB, Vacca JP, Liverton NJ (March 2010). “Discovery of vaniprevir (MK-7009), a macrocyclic hepatitis C virus NS3/4a protease inhibitor”. J. Med. Chem. 53 (6): 2443–63.doi:10.1021/jm9015526. PMID 20163176.
Song ZJ, Tellers DM, Journet M, Kuethe JT, Lieberman D, Humphrey G, Zhang F, Peng Z, Waters MS, Zewge D, Nolting A, Zhao D, Reamer RA, Dormer PG, Belyk KM, Davies IW, Devine PN, Tschaen DM.Synthesis of vaniprevir (MK-7009): lactamization to prepare a 20-membered [corrected] macrocycle.J Org Chem. 2011 Oct 7;76(19):7804-15. Epub 2011 Aug 31.
Abstract
Development of a practical synthesis of MK-7009, a 20-membered [corrected] macrocycle, is described. A variety of ring-closing strategies were evaluated, including ring-closing metathesis, intermolecular palladium-catalyzed cross-couplings, and macrolactamization. Ring closure via macrolactamization was found to give the highest yields under relatively high reaction concentrations. Optimization of the ring formation step and the synthesis of key intermediates en route to MK-7009 are reported
Abstract
Development of a practical synthesis of MK-7009, a 20-membered [corrected] macrocycle, is described. A variety of ring-closing strategies were evaluated, including ring-closing metathesis, intermolecular palladium-catalyzed cross-couplings, and macrolactamization. Ring closure via macrolactamization was found to give the highest yields under relatively high reaction concentrations. Optimization of the ring formation step and the synthesis of key intermediates en route to MK-7009 are reported
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Kong J, * Chen C.-y, * Balsells-Padros J, Cao Y, Dunn RF, Dolman SJ, Janey J, Li H, Zacuto MJ. Merck Research Laboratory, Rahway, USA
Synthesis of the HCV Protease Inhibitor Vaniprevir (MK-7009) Using Ring-Closing Metathesis Strategy.J. Org. Chem. 2012; 77: 3820-3828
Synthesis of the HCV Protease Inhibitor Vaniprevir (MK-7009) Using Ring-Closing Metathesis Strategy.J. Org. Chem. 2012; 77: 3820-3828
2,6-Dichloro-1,4-benzoquinone was added to suppress isomerization of the allyl alkene in the isoindoline unit in C and consequent competing formation of a 19-membered ring by-product. An important contributor to the success of the RCM reaction was the high purity of crystalline B…………………………………..
J. Org. Chem., 2012, 77 (8), pp 3820–3828
DOI: 10.1021/jo3001595
Filed under: Uncategorized Tagged: HCV protease inhibitors, macrocyclization, MK-7009, ring-closing metathesis, vaniprevir
