Antiinfectives for Systemic Use, 3. Antivirals
First published: 28 January 2022
Abstract
The article contains sections titled:
1 | Introduction |
2 | J05A Direct Acting Antivirals |
2.1 | J05AB Nucleosides and Nucleotides Excluding Reverse Transcriptase Inhibitors (RTIs) |
2.2 | J05AC Cyclic Amines |
2.3 | J05AD Phosphonic Acid Derivatives |
2.4 | J05AE Protease Inhibitors |
2.5 | J05AF Nucleoside and Nucleotide Reverse Transcriptase Inhibitors (NRTIs) |
2.6 | J05AG Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs) |
2.7 | J05AH Neuraminidase Inhibitors |
2.8 | J05AP Antivirals for Treatment of HCV Infections |
2.9 | J05AR Antivirals for Treatment of HIV Infections, Combinations |
2.10 | J05AX Other Antivirals |
List of Abbreviations | |
References |
References
- 1De Clercq, E. (2007) Three Decades of Antiviral Drugs, Nat. Rev. Drug Discov. 6, 941.
- 2De Clercq, E. (2007) The Design of Drugs for HIV and HCV, Nat. Rev. Drug Discov. 6, 1001–1018.
- 3Gable, J.E., et al. (2014) Current and Potential Treatments for Ubiquitous but Neglected Herpesvirus Infections, Chem. Rev. 114, 11382–11412.
- 4Jordheim, L.P., et al. (2013) Advances in the Development of Nucleoside and Nucleotide Analogues for Cancer and Viral Diseases, Nat. Rev. Drug Discov. 12, 447–464.
- 5Esposito, F., et al. (2012) HIV-1 Reverse Transcriptase Still Remains a New Drug Target: Structure, Function, Classical Inhibitors, and New Inhibitors with Innovative Mechanisms of Actions, Mol. Biol. Internat. 58640123. doi: 10.1155/2012/586401.
10.1155/2012/586401 Google Scholar
- 6Flexner, C. (2007) HIV Drug Development: The Next 25 Years, Nat. Rev. Drug Discov. 6, 959–966.
- 7Fraser, C., et al. (2014) Virulence and pathogenesis of HIV-1 infection: An evolutionary perspective, Science 343, 1243727-1-7. doi: 10.1126/science.1243727.
- 8Mehellou, Y. and De Clercq, E. (2010) Twenty-Six Years of Anti-HIV Drug Discovery: Where Do We Stand and Where Do We Go? J. Med. Chem. 53, 521–538.
- 9Oversteegen, L., et al. (2007) HIV Combination Products, Nat. Rev. Drug Discov. 6, 951–952.
- 10Wong, A. (2014) The HIV Pipeline, Nat. Rev. Drug Discov. 13, 649–650.
- 11Zhan, P., et al. (2016) Anti-HIV Drug Discovery and Development: Current Innovations and Future Trends, J. Med. Chem. 59, 2849–2878.
- 12 WHO (2015) Consolidated Guidelines on the Use of Antiretroviral Drugs for Treating and Preventing HIV Infection; What's New, WHO.
- 13Meanwell, N.A. and Watkins, W.J. (2014) Introduction to Hepatitis C Virus (HCV) Therapies Special Thematic Issue, J. Med. Chem. 57, 1625–1626. And following articles on new HCV therapeutics, e.g., Simeprevir, Asunaprevir, Danoprevir, Dasabuvir, Daclatasvir, Ledoipasvir and Ombitasvir.
- 14Cannalire, R., et al. (2016) A Journey Around The Medicinal Chemistry of Hepatitis C Virus Inhibitors Targeting NS4B: From Target to Preclinical Drug Candidates, J. Med. Chem. 59, 16–41.
- 15Manns, M.P., et al. (2007) The Way Forward in HCV Treatment–Finding the Right Path, Nat. Rev. Drug Discov. 6, 991–1000.
- 16Manns, M.P. and von Hahn, T. (2013) Novel Therapies for Hepatitis C – One Pill Fits All? Nat. Rev. Drug Discov. 12, 595–610.
- 17Sofia, M.J., et al. (2012) Nucleoside, Nucleotide, and Non-Nucleoside Inhibitors of Hepatitis C Virus NS5B RNA-Dependent RNA-Polymerase, J. Med. Chem. 55, 2481–2531.
- 18Schaeffer, H.J., et al. (1978) Nature 272, 583.
- 19 Wellcome, (1980) US 4 199 574, GB-prior. 1974.
- 20Chang, P.K. and Welch, A.D. (1963) J. Med. Chem. 6, 428.
- 21 Roussel-Uclaf, (1963) GB 1 024 156, FR-prior. 1962.
- 22Lee, W.W., et al. (1960) J. Am. Chem. Soc. 82, 2648.
- 23 Parke Davis, (1971) US 3 616 208, USA-prior. 1967.
- 24Schabel, F.M. Jr. (1968) Chemotherapy 13, 321.
- 25Witkowski, J.T., et al. (1972) J. Med. Chem. 15, 1150.
- 26 ICN, (1976) US 3 976 545, USA-prior. 1971.
- 27 ICN, (1979) US 4 138 547, USA-prior. 1977.
- 28Martin, J.C., et al. (1983) J. Med. Chem. 26, 759.
- 29 Syntex, (1983) US 4 355 032, USA-prior. 1981.
- 30 Syntex, (1983) US 4 423 050, USA-prior. 1981.
- 31 Syntex, (1985) US 4 507 305, USA-prior. 1981.
- 32Harnden, M.R., et al. (1989) J. Med. Chem. 32, 1738.
- 33 Beecham, (1993) US 5 246 937, GB-prior. 1985.
- 34 Co Pharma Corp, (1986) US 4 567 182, IT-prior. 1981.
- 35 Burroughs Wellcome (1990) US 4 957 924, USAprior. 1987.
- 36Snoeck, R., et al. (1988) Antimicrob, Agents Chemother. 32, 1839.
- 37 Ceskoslovenska Akad., (1992) US 5 142 051, CS-prior. 1986.
- 38Harnden, M.R., et al. (1987) J. Med. Chem. 30, 1636.
- 39 Beecham, (1991) US 5 075 445, GB-prior. 1983.
- 40 Roche, (1997) US 5 700 936; USA-prior. 1996.
- 41 Syntex, (2000) US 6 083 953; USA-prior. 1994.
- 42 Rega Inst.VZW, (1984) US 4 424 211, USA-prior. 1979.
- 43Eastman, R.T., et al. (2020) Remdesivir: A Review of Its Discovery and Development, ACS Central Sci. 6, 672–683.
- 44Siegel, D., et al. (2017) J. Med. Chem. 60, 1648–1661.
- 45Gilead, (2017) US 9 724 360, USA-prior. 2014.
- 46Coen, D.M. and Schaffer, P.A. (2003) Antiherpes Virus Drugs: A Promising Spectrum Of New Drugs And Drug Targets, Nat. Rev. Drug Discov. 2, 278–288.
- 47Elion, G.B. (1989) The Purine Path to Chemotherapy (Nobel Lecture), Angew. Chem. Int. Ed. 28, 870–878. (History of Aciclovir Discovery).
- 48 Du Pont, (1967) US 3 352 912, USA-prior. 1963.
- 49 Du Pont, (1971) US 3 592 934, USA-prior. 1963.
- 50 Du Pont, (1985) US 4 551 552, USA-prior. 1984.
- 51 Merz& Co., (1971) DE 1 941 218, DE-prior. 1969.
- 52Rosenthal, K.S., et al. (1982) Antimicrob. Agents Chemother. 22, 1031.
- 53Stetter, H., et al. (1960) Chem. Ber. 93, 226.
- 54 DuPont, (1967) US 3 310 469, USA-prior. 1961.
- 55Nylen, P. (1924) Ber. Dtsch. Chem. Ges. 57b, 1023.
- 56 DuPont, (1977) US 4 018 854, USA-prior. 1973.
- 57 Astra, (1982) US 4 339 445, SE-prior. 1976.
- 58Ghosh, A.K., et al. (2016) Recent Progress in the Development of HIV-1 Protease Inhibitors for the Treatment of HIV/AIDS, J. Med. Chem. ASAP. 59, 5172–5208.
- 59Ghosh, A.K., et al. (2012) Enhancing Protein Backbone Binding – A Fruitful Concept for Combating Drug-Resistant HIV, Angew. Chem. Int. Ed. 51, 1778–1802.
- 60Izawa, K. and Onishi, T. (2006) Industrial Syntheses of the Central Core Molecules of HIV Protease Inhibitors, Chem. Rev. 106, 2811–2827.
- 61Leung, D., et al. (2000) Protease Inhibitors: Current Status and Future Prospects, J. Med. Chem. 43, 305–341.
- 62Parkes, K.E.B., et al. (1994) J. Org. Chem. 59, 3656.
- 63 Roche, (1993) US 5 196 438; GB-prior. 1989.
- 64Dorsey, B.D., et al. (1994) J. Med. Chem. 37, 3443.
- 65 Merck & Co, (1995) US 5 413 999; USA-prior. 1991.
- 66Abbott, (1996) US 5 541 206, USA-prior. 1989.
- 67Abbott, (1996) US 5 567 823, USA-prior. 1995.
- 68Abbott, (1997) US 5 635 523, USA-prior. 1989.
- 69Abbott, (2005) US 6 894 171, USA-prior. 1998.
- 70Kaldar, S.W., et al. (1997) J. Med. Chem. 40, 3979.
- 71Agouron, (1996) US 5 484 926, USA-prior. 1993.
- 72Vertex, (1996) US 5 585 397, USA-prior. 1992.
- 73Stoner, E.J., et al. (1999) Org. Process Res. Dev. 3, 145. 4, 264 (2000).
- 74Abbott, (1999) US 5 914 332, USA-prior. 1995.
- 75Abbott, (2006) US 7 141 593, USA-prior. 1999.
- 76Vertex, (2002) US 6 436 989, USA-prior. 1997.
- 77Smith Kline Beecham, (2003) US 6 514 953, GB-prior. 1998.
- 78Bold, G., et al. (1998) J. Med. Chem. 41, 3387.
- 79Novartis, (1998) US 5 849 911, CH-prior. 1996.
- 80Bristol-Myers Squibb, (2000) US 6 087 383, USA-prior. 1998.
- 81Turner, S.R., et al. (1998) J. Med. Chem. 41, 3467.
- 82Fors, K.S., et al. (1998) J. Org. Chem. 63, 7348.
- 83Pharmacia & Upjohn, (1998) US 5 852 195, USA-prior. 1994.
- 84Upjohn Appl., (1995) EP 758 327, USA-prior. 1994.
- 85Gosh, A.K., et al. (2004) J. Org. Chem. 69, 7822.
- 86Gosh, A.K., et al. (2006) J. Med. Chem. 48, 5252.
- 87Tibotec, (2009) EP 1 725 566, EP-prior. 2003.
- 88Vertex, (2010) US 7 820 671, USA-prior. 2000.
- 89Venkatraman, S., et al. (2006) J. Med. Chem. 49, 6074.
- 90Schering-Plough, (2003) US 7 012 066, USA-prior. 2001.
- 91Schering-Plough, (2012) US RE 43298, USA-prior. 2000.
- 92Rosenquist, A., et al. (2014) J. Med. Chem. 57, 1673.
- 93Tibotec/Medivir, (2011) US 8 012 939, EP-prior. 2005.
- 94Glinski, R.P., et al. (1973) J. Org. Chem. 38, 4299.
- 95Horwitz, J.P., et al. (1964) J. Org. Chem. 29, 2076.
- 96Imazawa, M., et al. (1978) J. Org. Chem. 43, 3044.
- 97Burroughs Wellcome, (1988) US 4 724 232, GB-prior. 1985.
- 98McLaren, C., et al. (1991) Antiviral Chem. Chemother. 2, 321.
- 99Ajinomoto, (1990) US 4 970 148, JP-prior. 1987.
- 100Bristol-Myers Squibb, (1991) US 5 011 774, USA-prior. 1987.
- 101 US Dept. of Health, (1989) US 4 861 759, USA-prior. 1985.
- 102Lin, T.-S., et al. (1987) J. Med. Chem. 30, 440.
- 103US DHSS, (1989) US 4 879 277, USA-prior. 1985.
- 104Horwitz, J.P., et al. (1966) J. Org. Chem. 31, 205.
- 105Bristol-Myers, (1992) US 5 130 421, USA-prior. 1988.
- 106Beach, J.W., et al. (1992) J. Org. Chem. 57, 2217.
- 107IAF, (1991) US 5 047 407, USA-prior. 1989.
- 108Crimmins, M.T., et al. (1996) J. Org. Chem. 61, 4192.
- 109Burroughs Wellcome, (1991) US 5 034 394, GB prior. 1988.
- 110Glaxo SmithKline, (2002) US 6 417 191, GB-prior. 1995.
- 111Gilead, (1998) US 5 733 788, USA-prior. 1996.
- 112Gilead, (1999) US 5 922 695, USA-prior. 1996.
- 113Holy, A., et al. (1987) Collect, Czech. Chem. Commun. 52, 2801.
- 114Ceskoslov. akad. vet., (1989) US 4 808 716, CS-prior. 1985.
- 115Starrett, J.E., et al. (1994) J. Med. Chem. 37, 1857.
- 116Academy of Sci. of Czech Republic and Rega Stichting v.z.w., (1997) US 5 663 159, USA-prior. 1990.
- 117Jeong, L.S., et al. (1993) J. Med. Chem. 36, 181.
- 118Gaede, B.J., et al. (2005) Org. Proc. Res. & Dev. 9, 23.
- 119Emory Univ, (1993) US 5 210 085, USA-prior. 1990.
- 120BioChem Pharma, (1996) US 5 538 975, GB-prior. 1991.
- 121Emory Univ, (1998) US 5 814 639, USA-prior. 1990.
- 122Emory Univ, (1999) US 5 914 331, USA-prior. 1990.
- 123Bisacchi, G.S., et al. (1997) Bioorg, Med. Chem. Lett. 7, 127.
- 124Opio, C.K., et al. (2005) Nat. Rev./Drug Discov. 4, 535.
- 125BMS, (1993) US 5 206 244, USA-prior. 1990.
- 126Velasco, J., et al. (2013) J. Org. Chem. 78, 5482.
- 127Holy, A. (1972) Collect. Czech. Chem. Commun. 37, 4072.
- 128Idenix, (2003) US 6 596 700, USA-prior. 2000.
- 129Idenix, (2004) US 6 787 526, USA-prior. 2000.
- 130Gilead, (2010) US 7 803 788, USA-prior. 2000.
- 131Gilead, (2016) US 9 296 769, USA-prior. 2014.
- 132Derstine, B.P., et al. (2020) Org. Process Res. Dev. 24, 1420–1427.
- 133Hargrave, K.D., et al. (1991) J. Med. Chem. 34, 2231.
- 134Boehringer Ing, (1994) US 5 366 972, USA-prior. 1989.
- 135Romero, D.L., et al. (1993) J. Med. Chem. 36, 1505.
- 136Upjohn, (1996) US 5 563 142, USA-prior. 1989.
- 137Young, S.D., et al. (1995) Antimicrob. Agents Chemother. 39, 2602.
- 138Thompson, A.S., et al. (1995) Tetrahedron Lett. 36, 8937.
- 139Choudhury, A., et al. (2003) Org. Process Res. Dev. 7, 324.
- 140Merck & Co, (1996) US 5 519 021, USA-prior. 1992.
- 141Merck & Co, (1997) US 5 698 741, USA-prior. 1995.
- 142De Corte, B.L. (2005) J. Med. Chem. 48, 1689.
- 143Janssen, (2006) US 7 037 917, EP-prior. 1999
- 144Janssen, P.A.J., et al. (2005) J. Med. Chem. 48, 1901.
- 145Guillemont, J., et al. (2005) J. Med. Chem. 48, 2072.
- 146Janssen, (2006) US 7 125 879, EP-prior. 2001.
- 147MSD, (2013) US 8 486 975, USA-prior. 2010.
- 148Gauthier, D.R., et al. (2015) Org. Lett. 17, 1353–1356.
- 149Campeau, L.-C., et al. (2016) Org. Process Res. Dev. 20, 1476–1481.
- 150McMullen, J.P., et al. (2018) Org. Process Res. Dev. 22, 1208–1213.
- 151Enserink, M. (2013) Dueling Reviews for Controversial Flu Drug, Science 340, 508–509.
- 152von Itzstein, M. (2007) The War Against Influenza: Discovery and Development of Sialidase Inhibitors, Nat. Rev. Drug Discovery 6, 967–974.
- 153Biota, (1994) US 5 360 817, AUS-prior. 1990.
- 154Chandler, M., et al. (1995) J. Chem. Soc. Perkin Trans. 1, 1173.
- 155Gilead, (1998) US 5 763 483, USA-prior. 1995.
- 156Chand, P., et al. (2001) J. Med. Chem. 44, 4379–4392.
- 157Biocryst, (2003) US 6 562 861, USA-prior. 1997.
- 158Biocryst, (2014) US 8 778 997, USA-prior. 2006.
- 159Belema, M., et al. (2014) J. Med. Chem. 57, 2013.
- 160Belema, M., et al. (2014) J. Med. Chem. 57, 5057.
- 161BMS, (2012) US 8 303 944, USA-prior. 2006.
- 162Wang, P., et al. (2009) J. Org. Chem. 74, 6819–6824.
- 163Ross, B.S., et al. (2011) J. Org. Chem. 76, 8311–8319.
- 164Sofia, M., et al. (2010) J. Med. Chem. 53, 7202–7218.
- 165Pharmasset, (2010), US 7,964,580, US-prior. 2007.
- 166Abbott, (2012) US 8 188 104, USA-prior. 2007.
- 167AbbVie, (2013) US 8 501 238, USA-prior. 2007.
- 168Mangion, I.K., et al. (2014) Org. Lett. 16, 2310.
- 169Hughes, D.L. (2016) Org. Process Res. Dev. 20, 1404–1415.
- 170MSD, (2011) US 7 973 040, USA-prior. 2008.
- 171MSD, (2014) US 8 871 759, USA-prior. 2009.
- 172Harper, S., et al. (2012) ACS Med. Chem. Lett. 3, 332–336.
- 173Kuethe, J., et al. (2013) Org. Lett. 15, 4174–4177.
- 174Williams, M.J., et al. (2016) Org. Lett. 18, 1852–1955.
- 175Link, J.O., et al. (2014) J. Med. Chem. 57, 2033.
- 176Gilead, (2012) US 8 088 368, USA-prior. 2009.
- 177Gilead, (2014) US 8 822 430, USA-prior. 2009.
- 178Gilead Pharmasset, (2014) WO 2014 120981, USA-prior. 2013.
- 179DeGoey, D.A., et al. (2014) J. Med. Chem. 57, 2047.
- 180AbbVie, (2010) US 8 691 938, USA-prior. 2009.
- 181AbbVie, (2014) US 8 680 106, USA-prior. 2013.
- 182Abbott & Enanta, (2013) US 8 420 596, USA-prior. 2008.
- 183AbbVie, (2014) US 8 691 938, USA-prior. 2009.
- 184Gilead, (2013) US 8 575 135, USA-prior. 2011.
- 185Gilead, (2014) US 8 921 341, USA-prior. 2011.
- 186Gilead, (2017) US 9 655 944, USA-prior. 2012.
- 187Gilead, (2016), US 9 296 782, USA-prior. 2013.
- 188Enanta, (2015), US 9 220 748, USA-prior. 2011.
- 189Kallemeyn, J.M., et al. (2020) Development of a Large-Scale Route to Glecaprevir: Synthesis of the Macrocycle via Intramolecular Etherification, Org, Process Res. Dev. 24, 1373–1392.
- 190Hill, D.R., et al. (2020) Development of a Large-Scale Route to Glecaprevir: Synthesis of the Side Chain and Final Assembly, Org, Process Res. Dev. 24, 1393–1404.
- 191AbbVie, (2015) US 8 937 150, USA-prior. 2011.
- 192AbbVie, (2017) US 9 586 978, USA-prior. 2011.
- 193Di Santo, R. (2014) Inhibiting the HIV Integration Process: Past, Present, and the Future, J. Med. Chem. 57, 539–566.
- 194Palani, A. and Tagat, J.R. (2006) Discovery and Development of Small-Molecule Chemokine Coreceptor CCR5 Antagonists, J. Med. Chem. 49, 2851–2857.
- 195LaBonte, J., et al. (2003) Nat. Rev. Drug Discov. 2, 345.
- 196Matthews, T., et al. (2004) Nat. Rev. Drug Discov. 3, 215.
- 197Duke Univ, (1995) US 5 464 933, USA-prior. 1993.
- 198Trimeris, (2000) US 6 015 881, USA-prior. 1998.
- 199Duke Univ, (2000) US 6 133 418, USA-prior. 1995.
- 200Trimeris, (2002) US 6 475 491, USA-prior. 1995.
- 201Summa, V., et al. (2008) J. Med. Chem. 51, 5843.
- 202Humphrey, G.R., et al. (2011) Org. Process Res. Dev. 15, 73.
- 203 IRBM, (2007) US 7 169 780, USA-prior. 2001.
- 204Merck & Co, (2010) US 7 754 731, USA-prior. 2004.
- 205Pfizer, (2003) US 6 667 314, GB-prior. 2000.
- 206Pfizer, (2009) US 7 576 097, GB-prior. 2000.
- 207Satoh, M., et al. (2006) J. Med. Chem. 49, 1506.
- 208Japan Tobacco, (2007) US 7 176 220, JP-prior. 2002.
- 209Japan Tobacco, (2009) US 7 531 554, JP-prior. 2004.
- 210Johns, B.A., et al. (2013) J. Med. Chem. 56, 5901.
- 211Shionogi & GSK, (2012) US 8 129 385, JP-prior. 2005.
- 212Shionogi & ViiV, (2014) US 8 778 943, JP-prior. 2005.
- 213Trofimov, F.A. et al., inventors, (1993) (US 5 198 552), PCT/SU-prior. 1989.
- 214 Shenyang Pharmaceut. University, (2011) US “7 960 427”, CN-prior. 2004.
- 215 Shenyang Pharmaceut. University, (2006) EP appl. 1 731 506 A1, CN-prior. 2004.
- 216Lischka, P., et al. (2010) Antimicrob. Agents Chemother. 54, 1290.
- 217Humphrey, G.R., et al. (2016) Org. Process Res. Dev. 20, 1097–1103.
- 218Bayer, (2007) US 7 196 086, DE-prior. 2003.
- 219Aicuris, (2011) US 8 084 604, DE-prior. 2005.
- 220Aicuris, (2013) US 8 372 972, DE-prior. 2005.
- 221 Siga Technologies, (2010) US 7 737 168, USA-prior. 2003.
- 222 Siga Technologies, (2011) US 8 039 504, USA-prior. 2003.
- 223 Siga Technologies, (2013) US 8 530 509, USA-prior. 2003.
- 224 Siga Technologies, (2016) US 9 339 466, USA-prior. 2010.
- 225Hughes, D.L. (2019) Org. Process Res. Dev. 23, 1298–1307.
- 226 Shionogi, (2015) US 8 927 710, JP-prior. 2009.
- 227 Shionogi, (2015) US 8 987 441, JP-prior. 2010
- 228 Shionogi, (2017) US 9 815 835, JP-prior. 2009.
- 229Shionogi, (2019) US 10 392 406, JP-prior. 2015.
- 230Shionogi, (2020) US 10 759 814, JP-prior. 2016.
- 231Toyama Chemical, (2004) US 6 787 544, JP-prior. 1998, 1999.
- 232Toyama Chemical, (2004) US 6 800 629, JP-prior. 2000.
- 233Toyama Chemical, (2013), US 8 513 261, JP-prior. 2009.
- 234Fujifilm/Toyama Chemical, (2015) US 9 181 203, Jp-prior. 2010, 2011.
- 235MYR GmbH, (2018) EP appl. 3 392 267, EP-prior. 2017.
- 236MYR GmbH, (2021) US 10 925 925, EP-prior. 2017.
- 237MYR GmbH, (2018) US 2018/0228804 A1, EP-prior. 2014.
- 238MYR GmbH, (2018) US 2018/0296634 A1, EP-prior. 2017.
- 239MYR GmbH, (2016) WO 2016/055534 A2, EP-prior. 2014.
- 240Meanwell, N.A., et al. (2018) J. Med. Chem. 61, 62–80.
- 241Chen, K., et al. (2014) J. Org. Chem. 79, 8757–8767.
- 242 BMS-Team (2017) Comprehensive Description of Synthesis of BMS-663068 in 9 Parts, Org. Process Res. Dev. 21, 1091–1185.
- 243BMS, (2010) US 7 745 625, USA-prior. 2004.
- 244BMS, (2012) US 8 168 615, USA-prior. 2004.
- 245BMS, (2013) US 8 461 333, USA-prior. 2010.