Login Register Cart 0
Review Article

临床批准的蛋白酶抑制剂的结构-性质关系

卷 31, 期 12, 2024

发表于: 16 May, 2023

页: [1441 - 1463] 页: 23

弟呕挨: 10.2174/0929867330666230409232655

价格: $65

conference banner
摘要

背景：蛋白酶在许多生理过程的调节中发挥着重要作用，蛋白酶抑制剂已成为重要的药物类别之一。 特别是因为蛋白酶抑制剂的开发通常从基于底物的拟肽策略开始，因此许多最初的先导化合物都存在药代动力学缺陷。 目的：为了降低药物损耗率，将药物代谢和药代动力学研究充分融入现代药物发现研究，并通过构效关系阐明化学结构的修饰如何影响药物化合物的药代动力学和毒理学性质。 了解临床批准的蛋白酶抑制剂药物及其类似物的结构-性质关系可以为先导候选优化策略提供有用的信息。 方法：截至 2021 年底，约有 70 种针对人类或病原性病毒蛋白酶的抑制剂已获得批准。在本次综述中，由于详细的药理和/或理化数据已在药物化学中公开，因此选择 17 种抑制剂进行结构-性质关系分析 这些抑制剂及其类似物的文献。 结果：对汇编的数据进行分析，主要关注先导化合物中发现的药代动力学或毒理学缺陷以及用于生成候选化合物的结构修饰策略。 结论：构效关系总结了如何通过修饰蛋白酶抑制剂的结构成功地改善整体药性。 这些具体实例有望为今后开发新型蛋白酶抑制剂药物提供有益的参考和指导。

关键词: 结构-性质关系、蛋白酶抑制剂、肽模拟物、先导化合物优化、候选药物选择、药物发现。

« Previous Next »
[1]
Hughes, J.P.; Rees, S.; Kalindjian, S.B.; Philpott, K.L. Principles of early drug discovery. Br. J. Pharmacol., 2011, 162(6), 1239-1249.
[http://dx.doi.org/10.1111/j.1476-5381.2010.01127.x] [PMID: 21091654]
[2]
Veale, C.G.L. Into the fray! A beginner’s guide to medicinal chemistry. ChemMedChem, 2021, 16(8), 1199-1225.
[http://dx.doi.org/10.1002/cmdc.202000929] [PMID: 33591595]
[3]
Kenakin, T. Predicting therapeutic value in the lead optimization phase of drug discovery. Nat. Rev. Drug Discov., 2003, 2(6), 429-438.
[http://dx.doi.org/10.1038/nrd1110] [PMID: 12776218]
[4]
Jorgensen, W.L. Efficient drug lead discovery and optimization. Acc. Chem. Res., 2009, 42(6), 724-733.
[http://dx.doi.org/10.1021/ar800236t] [PMID: 19317443]
[5]
Leeson, P.D.; Springthorpe, B. The influence of drug-like concepts on decision-making in medicinal chemistry. Nat. Rev. Drug Discov., 2007, 6(11), 881-890.
[http://dx.doi.org/10.1038/nrd2445] [PMID: 17971784]
[6]
Leeson, P.D.; Bento, A.P.; Gaulton, A.; Hersey, A.; Manners, E.J.; Radoux, C.J.; Leach, A.R. Target-based evaluation of “drug-like” properties and ligand efficiencies. J. Med. Chem., 2021, 64(11), 7210-7230.
[http://dx.doi.org/10.1021/acs.jmedchem.1c00416] [PMID: 33983732]
[7]
Paul, S.M.; Mytelka, D.S.; Dunwiddie, C.T.; Persinger, C.C.; Munos, B.H.; Lindborg, S.R.; Schacht, A.L. How to improve R&D productivity: the pharmaceutical industry’s grand challenge. Nat. Rev. Drug Discov., 2010, 9(3), 203-214.
[http://dx.doi.org/10.1038/nrd3078] [PMID: 20168317]
[8]
Pammolli, F.; Magazzini, L.; Riccaboni, M. The productivity crisis in pharmaceutical R&D. Nat. Rev. Drug Discov., 2011, 10(6), 428-438.
[http://dx.doi.org/10.1038/nrd3405] [PMID: 21629293]
[9]
Chen, M.; Borlak, J.; Tong, W. High lipophilicity and high daily dose of oral medications are associated with significant risk for drug-induced liver injury. Hepatology, 2013, 58(1), 388-396.
[http://dx.doi.org/10.1002/hep.26208] [PMID: 23258593]
[10]
Gayvert, K.M.; Madhukar, N.S.; Elemento, O. A data-driven approach to predicting successes and failures of clinical trials. Cell Chem. Biol., 2016, 23(10), 1294-1301.
[http://dx.doi.org/10.1016/j.chembiol.2016.07.023] [PMID: 27642066]
[11]
Thompson, T.N. Optimization of metabolic stability as a goal of modern drug design. Med. Res. Rev., 2001, 21(5), 412-449.
[http://dx.doi.org/10.1002/med.1017] [PMID: 11579441]
[12]
Summerfield, S.; Jeffrey, P. Discovery DMPK: Changing paradigms in the eighties, nineties and noughties. Expert Opin. Drug Discov., 2009, 4(3), 207-218.
[http://dx.doi.org/10.1517/17460440902729405] [PMID: 23489121]
[13]
Ballard, P.; Brassil, P.; Bui, K.H.; Dolgos, H.; Petersson, C.; Tunek, A.; Webborn, P.J.H. The right compound in the right assay at the right time: An integrated discovery DMPK strategy. Drug Metab. Rev., 2012, 44(3), 224-252.
[http://dx.doi.org/10.3109/03602532.2012.691099] [PMID: 22697420]
[14]
Arnott, J.A.; Planey, S.L. The influence of lipophilicity in drug discovery and design. Expert Opin. Drug Discov., 2012, 7(10), 863-875.
[http://dx.doi.org/10.1517/17460441.2012.714363] [PMID: 22992175]
[15]
Miller, R.R.; Madeira, M.; Wood, H.B.; Geissler, W.M.; Raab, C.E.; Martin, I.J. Integrating the impact of lipophilicity on potency and pharmacokinetic parameters enables the use of diverse chemical space during small molecule drug optimization. J. Med. Chem., 2020, 63(21), 12156-12170.
[http://dx.doi.org/10.1021/acs.jmedchem.9b01813] [PMID: 32633947]
[16]
Choi, K. The structure–property relationships of clinically approved protein kinase inhibitors. Curr. Med. Chem., 2023, 30(22), 2518-2541.
[http://dx.doi.org/10.2174/0929867329666220822123552] [PMID: 35996243]
[17]
Choi, K. The structure–property relationships of GPCR-targeted drugs approved between 2011 and 2021. Curr. Med. Chem., 2023, 30(31)
[http://dx.doi.org/10.2174/1573399819666221102113217] [PMID: 36330638]
[18]
Ayala-Aguilera, C.C.; Valero, T.; Lorente-Macías, Á.; Baillache, D.J.; Croke, S.; Unciti-Broceta, A. small molecule kinase inhibitor drugs (1995–2021): Medical indication, pharmacology, and synthesis. J. Med. Chem., 2022, 65(2), 1047-1131.
[http://dx.doi.org/10.1021/acs.jmedchem.1c00963] [PMID: 34624192]
[19]
Roskoski, R., Jr Properties of FDA-approved small molecule protein kinase inhibitors: A 2022 update. Pharmacol. Res., 2022, 175, 106037.
[http://dx.doi.org/10.1016/j.phrs.2021.106037] [PMID: 34921994]
[20]
Congreve, M.; de Graaf, C.; Swain, N.A.; Tate, C.G. Impact of GPCR structures on drug discovery. Cell, 2020, 181(1), 81-91.
[http://dx.doi.org/10.1016/j.cell.2020.03.003] [PMID: 32243800]
[21]
Kooistra, A.J.; Mordalski, S.; Pándy-Szekeres, G.; Esguerra, M.; Mamyrbekov, A.; Munk, C.; Keserű, G.M.; Gloriam, D.E. GPCRdb in 2021: Integrating GPCR sequence, structure and function. Nucleic Acids Res., 2021, 49(D1), D335-D343.
[http://dx.doi.org/10.1093/nar/gkaa1080] [PMID: 33270898]
[22]
Leung, D.; Abbenante, G.; Fairlie, D.P. Protease inhibitors: Current status and future prospects. J. Med. Chem., 2000, 43(3), 305-341.
[http://dx.doi.org/10.1021/jm990412m] [PMID: 10669559]
[23]
Turk, B. Targeting proteases: Successes, failures and future prospects. Nat. Rev. Drug Discov., 2006, 5(9), 785-799.
[http://dx.doi.org/10.1038/nrd2092] [PMID: 16955069]
[24]
Al-Awadhi, F.H.; Luesch, H. Targeting eukaryotic proteases for natural products-based drug development. Nat. Prod. Rep., 2020, 37(6), 827-860.
[http://dx.doi.org/10.1039/C9NP00060G] [PMID: 32519686]
[25]
Weber, I.T.; Wang, Y.F.; Harrison, R.W. HIV protease: Historical perspective and current research. Viruses, 2021, 13(5), 839.
[http://dx.doi.org/10.3390/v13050839] [PMID: 34066370]
[26]
Kempf, D.J.; Marsh, K.C.; Denissen, J.F.; McDonald, E.; Vasavanonda, S.; Flentge, C.A.; Green, B.E.; Fino, L.; Park, C.H.; Kong, X.P. ABT-538 is a potent inhibitor of human immunodeficiency virus protease and has high oral bioavailability in humans. Proc. Natl. Acad. Sci., 1995, 92(7), 2484-2488.
[http://dx.doi.org/10.1073/pnas.92.7.2484] [PMID: 7708670]
[27]
Kempf, D.J.; Sham, H.L.; Marsh, K.C.; Flentge, C.A.; Betebenner, D.; Green, B.E.; McDonald, E.; Vasavanonda, S.; Saldivar, A.; Wideburg, N.E.; Kati, W.M.; Ruiz, L.; Zhao, C.; Fino, L.; Patterson, J.; Molla, A.; Plattner, J.J.; Norbeck, D.W. Discovery of ritonavir, a potent inhibitor of HIV protease with high oral bioavailability and clinical efficacy. J. Med. Chem., 1998, 41(4), 602-617.
[http://dx.doi.org/10.1021/jm970636+] [PMID: 9484509]
[28]
Kempf, D.J.; Marsh, K.C.; Fino, L.C.; Bryant, P.; Craig-Kennard, A.; Sham, H.L.; Zhao, C.; Vasavanonda, S.; Kohlbrenner, W.E.; Wideburg, N.E.; Saldivar, A.; Green, B.E.; Herrin, T.; Norbeck, D.W. Design of orally bioavailable, symmetry-based inhibitors of HIV protease. Bioorg. Med. Chem., 1994, 2(9), 847-858.
[http://dx.doi.org/10.1016/S0968-0896(00)82036-2] [PMID: 7712122]
[29]
Kempf, D.J.; Marsh, K.C.; Kumar, G.; Rodrigues, A.D.; Denissen, J.F.; McDonald, E.; Kukulka, M.J.; Hsu, A.; Granneman, G.R.; Baroldi, P.A.; Sun, E.; Pizzuti, D.; Plattner, J.J.; Norbeck, D.W.; Leonard, J.M. Pharmacokinetic enhancement of inhibitors of the human immunodeficiency virus protease by coadministration with ritonavir. Antimicrob. Agents Chemother., 1997, 41(3), 654-660.
[http://dx.doi.org/10.1128/AAC.41.3.654] [PMID: 9056009]
[30]
Sevrioukova, I.F.; Poulos, T.L. Structure and mechanism of the complex between cytochrome P4503A4 and ritonavir. Proc. Natl. Acad. Sci., 2010, 107(43), 18422-18427.
[http://dx.doi.org/10.1073/pnas.1010693107] [PMID: 20937904]
[31]
Deeks, E.D. Ombitasvir/paritaprevir/ritonavir plus dasabuvir: A review in chronic HCV genotype 1 infection. Drugs, 2015, 75(9), 1027-1038.
[http://dx.doi.org/10.1007/s40265-015-0412-z] [PMID: 26059288]
[32]
Owen, D.R.; Allerton, C.M.N.; Anderson, A.S.; Aschenbrenner, L.; Avery, M.; Berritt, S.; Boras, B.; Cardin, R.D.; Carlo, A.; Coffman, K.J.; Dantonio, A.; Di, L.; Eng, H.; Ferre, R.; Gajiwala, K.S.; Gibson, S.A.; Greasley, S.E.; Hurst, B.L.; Kadar, E.P.; Kalgutkar, A.S.; Lee, J.C.; Lee, J.; Liu, W.; Mason, S.W.; Noell, S.; Novak, J.J.; Obach, R.S.; Ogilvie, K.; Patel, N.C.; Pettersson, M.; Rai, D.K.; Reese, M.R.; Sammons, M.F.; Sathish, J.G.; Singh, R.S.P.; Steppan, C.M.; Stewart, A.E.; Tuttle, J.B.; Updyke, L.; Verhoest, P.R.; Wei, L.; Yang, Q.; Zhu, Y. An oral SARS-CoV-2 M pro inhibitor clinical candidate for the treatment of COVID-19. Science, 2021, 374(6575), 1586-1593.
[http://dx.doi.org/10.1126/science.abl4784] [PMID: 34726479]
[33]
Lyle, T.A.; Wiscount, C.M.; Guare, J.P.; Thompson, W.J.; Anderson, P.S.; Darke, P.L.; Zugay, J.A.; Emini, E.A.; Schleif, W.A.; Qunitero, J.C. Benzocycloalkyl amines as novel C-termini for HIV protease inhibitors. J. Med. Chem., 1991, 34(3), 1228-1230.
[http://dx.doi.org/10.1021/jm00107a051] [PMID: 2002466]
[34]
Thompson, W.J.; Fitzgerald, P.M.D.; Holloway, M.K.; Emini, E.A.; Darke, P.L.; McKeever, B.M.; Schleif, W.A.; Quintero, J.C.; Zugay, J.A. Synthesis and antiviral activity of a series of HIV-1 protease inhibitors with functionality tethered to the P1 or P1′ phenyl design. J. Med. Chem., 1992, 35(10), 1685-1701.
[http://dx.doi.org/10.1021/jm00088a003] [PMID: 1588551]
[35]
Vacca, J.P.; Dorsey, B.D.; Schleif, W.A.; Levin, R.B.; McDaniel, S.L.; Darke, P.L.; Zugay, J.; Quintero, J.C.; Blahy, O.M.; Roth, E. L-735,524: an orally bioavailable human immunodeficiency virus type 1 protease inhibitor. Proc. Natl. Acad. Sci. USA, 1994, 91(9), 4096-4100.
[http://dx.doi.org/10.1073/pnas.91.9.4096] [PMID: 8171040]
[36]
Dorsey, B.D.; Levin, R.B.; McDaniel, S.L.; Vacca, J.P.; Guare, J.P.; Darke, P.L.; Zugay, J.A.; Emini, E.A.; Schleif, W.A.; Quintero, J.C. L-735,524: the design of a potent and orally bioavailable HIV protease inhibitor. J. Med. Chem., 1994, 37(21), 3443-3451.
[http://dx.doi.org/10.1021/jm00047a001] [PMID: 7932573]
[37]
Munshi, S.; Chen, Z.; Li, Y.; Olsen, D.B.; Fraley, M.E.; Hungate, R.W.; Kuo, L.C. Rapid X-ray diffraction analysis of HIV-1 protease–inhibitor complexes: inhibitor exchange in single crystals of the bound enzyme. Acta Crystallogr. D Biol. Crystallogr., 1998, 54(5), 1053-1060.
[http://dx.doi.org/10.1107/S0907444998003588] [PMID: 9757136]
[38]
Ghosh, A.K.; Kincaid, J.F.; Cho, W.; Walters, D.E.; Krishnan, K.; Hussain, K.A.; Koo, Y.; Cho, H.; Rudall, C.; Holland, L.; Buthod, J. Potent HIV protease inhibitors incorporating high-affinity P2-ligands and (R)-(hydroxyethylamino)sulfonamide isostere. Bioorg. Med. Chem. Lett., 1998, 8(6), 687-690.
[http://dx.doi.org/10.1016/S0960-894X(98)00098-5] [PMID: 9871583]
[39]
Surleraux, D.L.N.G.; Tahri, A.; Verschueren, W.G.; Pille, G.M.E.; de Kock, H.A.; Jonckers, T.H.M.; Peeters, A.; De Meyer, S.; Azijn, H.; Pauwels, R.; de Bethune, M.P.; King, N.M.; Prabu-Jeyabalan, M.; Schiffer, C.A.; Wigerinck, P.B.T.P. Discovery and selection of TMC114, a next generation HIV-1 protease inhibitor. J. Med. Chem., 2005, 48(6), 1813-1822.
[http://dx.doi.org/10.1021/jm049560p] [PMID: 15771427]
[40]
Kim, E.E.; Baker, C.T.; Dwyer, M.D.; Murcko, M.A.; Rao, B.G.; Tung, R.D.; Navia, M.A. Crystal structure of HIV-1 protease in complex with VX-478, a potent and orally bioavailable inhibitor of the enzyme. J. Am. Chem. Soc., 1995, 117(3), 1181-1182.
[http://dx.doi.org/10.1021/ja00108a056]
[41]
Tie, Y.; Boross, P.I.; Wang, Y.F.; Gaddis, L.; Hussain, A.K.; Leshchenko, S.; Ghosh, A.K.; Louis, J.M.; Harrison, R.W.; Weber, I.T. High resolution crystal structures of HIV-1 protease with a potent non-peptide inhibitor (UIC-94017) active against multi-drug-resistant clinical strains. J. Mol. Biol., 2004, 338(2), 341-352.
[http://dx.doi.org/10.1016/j.jmb.2004.02.052] [PMID: 15066436]
[42]
Kawabata, K.; Suzuki, M.; Sugitani, M.; Imaki, K.; Toda, M.; Miyamoto, T. ONO-5046, a novel inhibitor of human neutrophil elastase. Biochem. Biophys. Res. Commun., 1991, 177(2), 814-820.
[http://dx.doi.org/10.1016/0006-291X(91)91862-7] [PMID: 2049103]
[43]
Imaki, K.; Okada, T.; Nakayama, Y.; Nagao, Y.; Kobayashi, K.; Sakai, Y.; Mohri, T.; Amino, T.; Nakai, H.; Kawamura, M. Non-peptidic inhibitors of human neutrophil elastase: The design and synthesis of sulfonanilide-containing inhibitors. Bioorg. Med. Chem., 1996, 4(12), 2115-2134.
[http://dx.doi.org/10.1016/S0968-0896(96)00216-7] [PMID: 9022976]
[44]
Gallwitz, B. Clinical use of DPP-4 inhibitors. Front. Endocrinol., 2019, 10, 389.
[http://dx.doi.org/10.3389/fendo.2019.00389] [PMID: 31275246]
[45]
Xu, J.; Ok, H.O.; Gonzalez, E.J.; Colwell, L.F., Jr; Habulihaz, B.; He, H.; Leiting, B.; Lyons, K.A.; Marsilio, F.; Patel, R.A.; Wu, J.K.; Thornberry, N.A.; Weber, A.E.; Parmee, E.R. Discovery of potent and selective β-homophenylalanine based dipeptidyl peptidase IV inhibitors. Bioorg. Med. Chem. Lett., 2004, 14(18), 4759-4762.
[http://dx.doi.org/10.1016/j.bmcl.2004.06.099] [PMID: 15324903]
[46]
Brockunier, L.L.; He, J.; Colwell, L.F., Jr; Habulihaz, B.; He, H.; Leiting, B.; Lyons, K.A.; Marsilio, F.; Patel, R.A.; Teffera, Y.; Wu, J.K.; Thornberry, N.A.; Weber, A.E.; Parmee, E.R. Substituted piperazines as novel dipeptidyl peptidase IV inhibitors. Bioorg. Med. Chem. Lett., 2004, 14(18), 4763-4766.
[http://dx.doi.org/10.1016/j.bmcl.2004.06.065] [PMID: 15324904]
[47]
Kim, D.; Wang, L.; Beconi, M.; Eiermann, G.J.; Fisher, M.H.; He, H.; Hickey, G.J.; Kowalchick, J.E.; Leiting, B.; Lyons, K.; Marsilio, F.; McCann, M.E.; Patel, R.A.; Petrov, A.; Scapin, G.; Patel, S.B.; Roy, R.S.; Wu, J.K.; Wyvratt, M.J.; Zhang, B.B.; Zhu, L.; Thornberry, N.A.; Weber, A.E. (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine: a potent, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. J. Med. Chem., 2005, 48(1), 141-151.
[http://dx.doi.org/10.1021/jm0493156] [PMID: 15634008]
[48]
Eckhardt, M.; Langkopf, E.; Mark, M.; Tadayyon, M.; Thomas, L.; Nar, H.; Pfrengle, W.; Guth, B.; Lotz, R.; Sieger, P.; Fuchs, H.; Himmelsbach, F. 8-(3-(R)-aminopiperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydropurine-2,6-dione (BI 1356), a highly potent, selective, long-acting, and orally bioavailable DPP-4 inhibitor for the treatment of type 2 diabetes. J. Med. Chem., 2007, 50(26), 6450-6453.
[http://dx.doi.org/10.1021/jm701280z] [PMID: 18052023]
[49]
Thomas, L.; Eckhardt, M.; Langkopf, E.; Tadayyon, M.; Himmelsbach, F.; Mark, M. (R)-8-(3-amino-piperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydro-purine-2,6-dione (BI 1356), a novel xanthine-based dipeptidyl peptidase 4 inhibitor, has a superior potency and longer duration of action compared with other dipeptidyl peptidase-4 inhibitors. J. Pharmacol. Exp. Ther., 2008, 325(1), 175-182.
[http://dx.doi.org/10.1124/jpet.107.135723] [PMID: 18223196]
[50]
Kato, N.; Oka, M.; Murase, T.; Yoshida, M.; Sakairi, M.; Yakufu, M.; Yamashita, S.; Yasuda, Y.; Yoshikawa, A.; Hayashi, Y.; Shirai, M.; Mizuno, Y.; Takeuchi, M.; Makino, M.; Takeda, M.; Kakigami, T. Synthesis and pharmacological characterization of potent, selective, and orally bioavailable isoindoline class dipeptidyl peptidase IV inhibitors. Org. Med. Chem. Lett., 2011, 1(1), 7.
[http://dx.doi.org/10.1186/2191-2858-1-7] [PMID: 22373386]
[51]
Kato, N.; Oka, M.; Murase, T.; Yoshida, M.; Sakairi, M.; Yamashita, S.; Yasuda, Y.; Yoshikawa, A.; Hayashi, Y.; Makino, M.; Takeda, M.; Mirensha, Y.; Kakigami, T. Discovery and pharmacological characterization of N-[2-({2-[(2S)-2-cyanopyrrolidin-1-yl]-2-oxoethyl}amino)-2-methylpropyl]-2-methylpyrazolo[1,5-a]pyrimidine-6-carboxamide hydrochloride (anagliptin hydrochloride salt) as a potent and selective DPP-IV inhibitor. Bioorg. Med. Chem. Lett., 2011, 19(23), 7221-7227.
[http://dx.doi.org/10.1016/j.bmc.2011.09.043] [PMID: 22019046]
[52]
Furuta, S.; Smart, C.; Hackett, A.; Benning, R.; Warrington, S. Pharmacokinetics and metabolism of [14C] anagliptin, a novel dipeptidyl peptidase-4 inhibitor, in humans. Xenobiotica, 2013, 43(5), 432-442.
[http://dx.doi.org/10.3109/00498254.2012.731618] [PMID: 23075005]
[53]
Nabeno, M.; Akahoshi, F.; Kishida, H.; Miyaguchi, I.; Tanaka, Y.; Ishii, S.; Kadowaki, T. A comparative study of the binding modes of recently launched dipeptidyl peptidase IV inhibitors in the active site. Biochem. Biophys. Res. Commun., 2013, 434(2), 191-196.
[http://dx.doi.org/10.1016/j.bbrc.2013.03.010] [PMID: 23501107]
[54]
Metzler, W.J.; Yanchunas, J.; Weigelt, C.; Kish, K.; Klei, H.E.; Xie, D.; Zhang, Y.; Corbett, M.; Tamura, J.K.; He, B.; Hamann, L.G.; Kirby, M.S.; Marcinkeviciene, J. Involvement of DPP-IV catalytic residues in enzyme-saxagliptin complex formation. Protein Sci., 2008, 17(2), 240-250.
[http://dx.doi.org/10.1110/ps.073253208] [PMID: 18227430]
[55]
Watanabe, Y.S.; Yasuda, Y.; Kojima, Y.; Okada, S.; Motoyama, T.; Takahashi, R.; Oka, M. Anagliptin, a potent dipeptidyl peptidase IV inhibitor: its single-crystal structure and enzyme interactions. J. Enzyme Inhib. Med. Chem., 2015, 30(6), 981-988.
[http://dx.doi.org/10.3109/14756366.2014.1002402] [PMID: 26147347]
[56]
Kong, F.; Pang, X.; Zhao, J.; Deng, P.; Zheng, M.; Zhong, D.; Chen, X. Hydrolytic metabolism of cyanopyrrolidine DPP-4 inhibitors mediated by dipeptidyl peptidases. Drug Metab. Dispos., 2019, 47(3), 238-248.
[http://dx.doi.org/10.1124/dmd.118.084640] [PMID: 30530814]
[57]
Feng, J.; Zhang, Z.; Wallace, M.B.; Stafford, J.A.; Kaldor, S.W.; Kassel, D.B.; Navre, M.; Shi, L.; Skene, R.J.; Asakawa, T.; Takeuchi, K.; Xu, R.; Webb, D.R.; Gwaltney, S.L., II Discovery of alogliptin: A potent, selective, bioavailable, and efficacious inhibitor of dipeptidyl peptidase IV. J. Med. Chem., 2007, 50(10), 2297-2300.
[http://dx.doi.org/10.1021/jm070104l] [PMID: 17441705]
[58]
Zhang, Z.; Wallace, M.B.; Feng, J.; Stafford, J.A.; Skene, R.J.; Shi, L.; Lee, B.; Aertgeerts, K.; Jennings, A.; Xu, R.; Kassel, D.B.; Kaldor, S.W.; Navre, M.; Webb, D.R.; Gwaltney, S.L., II Design and synthesis of pyrimidinone and pyrimidinedione inhibitors of dipeptidyl peptidase IV. J. Med. Chem., 2011, 54(2), 510-524.
[http://dx.doi.org/10.1021/jm101016w] [PMID: 21186796]
[59]
Covington, P.; Christopher, R.; Davenport, M.; Fleck, P.; Mekki, Q.; Wann, E.; Karim, A. Pharmacokinetic, pharmacodynamic, and tolerability profiles of the dipeptidyl peptidase-4 inhibitor alogliptin: A randomized, double-blind, placebo-controlled, multiple-dose study in adult patients with type 2 diabetes. Clin. Ther., 2008, 30(3), 499-512.
[http://dx.doi.org/10.1016/j.clinthera.2008.03.004] [PMID: 18405788]
[60]
Inagaki, N.; Onouchi, H.; Sano, H.; Funao, N.; Kuroda, S.; Kaku, K. SYR-472, a novel once-weekly dipeptidyl peptidase-4 (DPP-4) inhibitor, in type 2 diabetes mellitus: A phase 2, randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol., 2014, 2(2), 125-132.
[http://dx.doi.org/10.1016/S2213-8587(13)70149-9] [PMID: 24622716]
[61]
Grimshaw, C.E.; Jennings, A.; Kamran, R.; Ueno, H.; Nishigaki, N.; Kosaka, T.; Tani, A.; Sano, H.; Kinugawa, Y.; Koumura, E.; Shi, L.; Takeuchi, K. Trelagliptin (SYR-472, Zafatek), novel once-weekly treatment for type 2 diabetes, inhibits dipeptidyl peptidase-4 (DPP-4) via a non-covalent mechanism. PLoS One, 2016, 11(6), e0157509.
[http://dx.doi.org/10.1371/journal.pone.0157509] [PMID: 27328054]
[62]
Inagaki, N.; Onouchi, H.; Maezawa, H.; Kuroda, S.; Kaku, K. Once-weekly trelagliptin versus daily alogliptin in Japanese patients with type 2 diabetes: A randomised, double-blind, phase 3, non-inferiority study. Lancet Diabetes Endocrinol., 2015, 3(3), 191-197.
[http://dx.doi.org/10.1016/S2213-8587(14)70251-7] [PMID: 25609193]
[63]
Inagaki, N.; Sano, H.; Seki, Y.; Kuroda, S.; Kaku, K. Efficacy and safety of once-weekly oral trelagliptin switched from once-daily dipeptidyl peptidase-4 inhibitor in patients with type 2 diabetes mellitus: An open-label, phase 3 exploratory study. J. Diabetes Investig., 2018, 9(2), 354-359.
[http://dx.doi.org/10.1111/jdi.12730] [PMID: 28836351]
[64]
McKeage, K.; Plosker, G.L. Argatroban. Drugs, 2001, 61(4), 515-522.
[http://dx.doi.org/10.2165/00003495-200161040-00005] [PMID: 11324681]
[65]
Hauel, N.H.; Nar, H.; Priepke, H.; Ries, U.; Stassen, J.M.; Wienen, W. Structure-based design of novel potent nonpeptide thrombin inhibitors. J. Med. Chem., 2002, 45(9), 1757-1766.
[http://dx.doi.org/10.1021/jm0109513] [PMID: 11960487]
[66]
Ansell, J. Factor Xa or thrombin: Is factor Xa a better target? J. Thromb. Haemost., 2007, 5(S1), 60-64.
[http://dx.doi.org/10.1111/j.1538-7836.2007.02473.x] [PMID: 17635710]
[67]
Pinto, D.J.P.; Smallheer, J.M.; Cheney, D.L.; Knabb, R.M.; Wexler, R.R. Factor Xa inhibitors: Next-generation antithrombotic agents. J. Med. Chem., 2010, 53(17), 6243-6274.
[http://dx.doi.org/10.1021/jm100146h] [PMID: 20503967]
[68]
Patel, N.R.; Patel, D.V.; Murumkar, P.R.; Yadav, M.R. Contemporary developments in the discovery of selective factor Xa inhibitors: A review. Eur. J. Med. Chem., 2016, 121, 671-698.
[http://dx.doi.org/10.1016/j.ejmech.2016.05.039] [PMID: 27322757]
[69]
Perzborn, E.; Roehrig, S.; Straub, A.; Kubitza, D.; Misselwitz, F. The discovery and development of rivaroxaban, an oral, direct factor Xa inhibitor. Nat. Rev. Drug Discov., 2011, 10(1), 61-75.
[http://dx.doi.org/10.1038/nrd3185] [PMID: 21164526]
[70]
Roehrig, S.; Straub, A.; Pohlmann, J.; Lampe, T.; Pernerstorfer, J.; Schlemmer, K.H.; Reinemer, P.; Perzborn, E. Discovery of the novel antithrombotic agent 5-Chloro- N -((5 S )-2-oxo-3- [4-(3-oxomorpholin-4-yl)phenyl]-1,3-oxazolidin-5-ylmethyl)thiophene- 2-carboxamide (BAY 59-7939): An oral, direct factor Xa inhibitor. J. Med. Chem., 2005, 48(19), 5900-5908.
[http://dx.doi.org/10.1021/jm050101d] [PMID: 16161994]
[71]
Weinz, C.; Buetehorn, U.; Daehler, H.P.; Kohlsdorfer, C.; Pleiss, U.; Sandmann, S.; Schlemmer, K.H.; Schwarz, T.; Steinke, W. Pharmacokinetics of BAY 59-7939 – an oral, direct factor Xa inhibitor – in rats and dogs. Xenobiotica, 2005, 35(9), 891-910.
[http://dx.doi.org/10.1080/00498250500250493] [PMID: 16308283]
[72]
Zhang, Q.; Xu, Z.; Zhu, W. The underestimated halogen bonds forming with protein side chains in drug discovery and design. J. Chem. Inf. Model., 2017, 57(1), 22-26.
[http://dx.doi.org/10.1021/acs.jcim.6b00628] [PMID: 27990818]
[73]
Costa, P.J.; Nunes, R.; Vila-Viçosa, D. Halogen bonding in halocarbon-protein complexes and computational tools for rational drug design. Expert Opin. Drug Discov., 2019, 14(8), 805-820.
[http://dx.doi.org/10.1080/17460441.2019.1619692] [PMID: 31131651]
[74]
Pinto, D.J.P.; Orwat, M.J.; Quan, M.L.; Han, Q.; Galemmo, R.A., Jr; Amparo, E.; Wells, B.; Ellis, C.; He, M.Y.; Alexander, R.S.; Rossi, K.A.; Smallwood, A.; Wong, P.C.; Luettgen, J.M.; Rendina, A.R.; Knabb, R.M.; Mersinger, L.; Kettner, C.; Bai, S.; He, K.; Wexler, R.R.; Lam, P.Y.S. 1-[3-Aminobenzisoxazol-5′-yl]-3-trifluoromethyl-6-[2′-(3-(R)-hydroxy-N-pyrrolidinyl)methyl-[1,1′]-biphen-4-yl]-1,4,5,6-tetrahydropyrazolo-[3,4-c]-pyridin-7-one (BMS-740808) a highly potent, selective, efficacious, and orally bioavailable inhibitor of blood coagulation factor Xa. Bioorg. Med. Chem. Lett., 2006, 16(15), 4141-4147.
[http://dx.doi.org/10.1016/j.bmcl.2006.02.069] [PMID: 16730984]
[75]
Pinto, D.J.P.; Galemmo, R.A., Jr; Quan, M.L.; Orwat, M.J.; Clark, C.; Li, R.; Wells, B.; Woerner, F.; Alexander, R.S.; Rossi, K.A.; Smallwood, A.; Wong, P.C.; Luettgen, J.M.; Rendina, A.R.; Knabb, R.M.; He, K.; Wexler, R.R.; Lam, P.Y.S. Discovery of potent, efficacious, and orally bioavailable inhibitors of blood coagulation factor Xa with neutral P1 moieties. Bioorg. Med. Chem. Lett., 2006, 16(21), 5584-5589.
[http://dx.doi.org/10.1016/j.bmcl.2006.08.027] [PMID: 16963264]
[76]
Pinto, D.J.P.; Orwat, M.J.; Koch, S.; Rossi, K.A.; Alexander, R.S.; Smallwood, A.; Wong, P.C.; Rendina, A.R.; Luettgen, J.M.; Knabb, R.M.; He, K.; Xin, B.; Wexler, R.R.; Lam, P.Y.S. Discovery of 1-(4-methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl)phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide (apixaban, BMS-562247), a highly potent, selective, efficacious, and orally bioavailable inhibitor of blood coagulation factor Xa. J. Med. Chem., 2007, 50(22), 5339-5356.
[http://dx.doi.org/10.1021/jm070245n] [PMID: 17914785]
[77]
Straub, A.; Roehrig, S.; Hillisch, A. Oral, direct thrombin and factor Xa inhibitors: The replacement for warfarin, leeches, and pig intestines? Angew. Chem. Int. Ed., 2011, 50(20), 4574-4590.
[http://dx.doi.org/10.1002/anie.201004575] [PMID: 21538731]
[78]
Xie, Z.; Tian, Y.; Lv, X.; Xiao, X.; Zhan, M.; Cheng, K.; Li, S.; Liao, C. The selectivity and bioavailability improvement of novel oral anticoagulants: An overview. Eur. J. Med. Chem., 2018, 146, 299-317.
[http://dx.doi.org/10.1016/j.ejmech.2018.01.067] [PMID: 29407959]
[79]
Zhu, B.Y.; Jia, Z.J.; Zhang, P.; Su, T.; Huang, W.; Goldman, E.; Tumas, D.; Kadambi, V.; Eddy, P.; Sinha, U.; Scarborough, R.M.; Song, Y. Inhibitory effect of carboxylic acid group on hERG binding. Bioorg. Med. Chem. Lett., 2006, 16(21), 5507-5512.
[http://dx.doi.org/10.1016/j.bmcl.2006.08.039] [PMID: 16931010]
[80]
Zhang, P.; Huang, W.; Wang, L.; Bao, L.; Jia, Z.J.; Bauer, S.M.; Goldman, E.A.; Probst, G.D.; Song, Y.; Su, T.; Fan, J.; Wu, Y.; Li, W.; Woolfrey, J.; Sinha, U.; Wong, P.W.; Edwards, S.T.; Arfsten, A.E.; Clizbe, L.A.; Kanter, J.; Pandey, A.; Park, G.; Hutchaleelaha, A.; Lambing, J.L.; Hollenbach, S.J.; Scarborough, R.M.; Zhu, B.Y. Discovery of betrixaban (PRT054021), N-(5-chloropyridin-2-yl)-2-(4-(N,N-dimethylcarbamimidoyl)benzamido)-5-methoxybenzamide, a highly potent, selective, and orally efficacious factor Xa inhibitor. Bioorg. Med. Chem. Lett., 2009, 19(8), 2179-2185.
[http://dx.doi.org/10.1016/j.bmcl.2009.02.111] [PMID: 19297154]
[81]
Zhang, P.; Bao, L.; Fan, J.; Jia, Z.J.; Sinha, U.; Wong, P.W.; Park, G.; Hutchaleelaha, A.; Scarborough, R.M.; Zhu, B.Y. Anthranilamide-based N,N-dialkylbenzamidines as potent and orally bioavailable factor Xa inhibitors: P4 SAR. Bioorg. Med. Chem. Lett., 2009, 19(8), 2186-2189.
[http://dx.doi.org/10.1016/j.bmcl.2009.02.114] [PMID: 19297158]
[82]
Adler, M.; Kochanny, M.J.; Ye, B.; Rumennik, G.; Light, D.R.; Biancalana, S.; Whitlow, M. Crystal structures of two potent nonamidine inhibitors bound to factor Xa. Biochemistry, 2002, 41(52), 15514-15523.
[http://dx.doi.org/10.1021/bi0264061] [PMID: 12501180]
[83]
Ye, B.; Arnaiz, D.O.; Chou, Y.L.; Griedel, B.D.; Karanjawala, R.; Lee, W.; Morrissey, M.M.; Sacchi, K.L.; Sakata, S.T.; Shaw, K.J.; Wu, S.C.; Zhao, Z.; Adler, M.; Cheeseman, S.; Dole, W.P.; Ewing, J.; Fitch, R.; Lentz, D.; Liang, A.; Light, D.; Morser, J.; Post, J.; Rumennik, G.; Subramanyam, B.; Sullivan, M.E.; Vergona, R.; Walters, J.; Wang, Y.X.; White, K.A.; Whitlow, M.; Kochanny, M.J. Thiophene-anthranilamides as highly potent and orally available factor Xa inhibitors. J. Med. Chem., 2007, 50(13), 2967-2980.
[http://dx.doi.org/10.1021/jm070125f] [PMID: 17536795]
[84]
Zhang, J.; Krishnan, R.; Arnold, C.; Mattsson, E.; Kilpatrick, J.; Bantia, S.; Dehghani, A.; Boudreaux, B.; Gupta, S.; Kotian, P.L.; Chand, P.; Babu, Y.S. Discovery of highly potent small molecule kallikrein inhibitors. Med. Chem., 2006, 2(6), 545-553.
[http://dx.doi.org/10.2174/1573406410602060545] [PMID: 17105435]
[85]
Riedl, M.A.; Aygören-Pürsün, E.; Baker, J.; Farkas, H.; Anderson, J.; Bernstein, J.A.; Bouillet, L.; Busse, P.; Manning, M.; Magerl, M.; Gompels, M.; Huissoon, A.P.; Longhurst, H.; Lumry, W.; Ritchie, B.; Shapiro, R.; Soteres, D.; Banerji, A.; Cancian, M.; Johnston, D.T.; Craig, T.J.; Launay, D.; Li, H.H.; Liebhaber, M.; Nickel, T.; Offenberger, J.; Rae, W.; Schrijvers, R.; Triggiani, M.; Wedner, H.J.; Dobo, S.; Cornpropst, M.; Clemons, D.; Fang, L.; Collis, P.; Sheridan, W.P.; Maurer, M. Evaluation of avoralstat, an oral kallikrein inhibitor, in a phase 3 hereditary angioedema prophylaxis trial: The OPuS-2 study. Allergy, 2018, 73(9), 1871-1880.
[http://dx.doi.org/10.1111/all.13466] [PMID: 29688579]
[86]
Kotian, P.L.; Wu, M.; Vadlakonda, S.; Chintareddy, V.; Lu, P.; Juarez, L.; Kellogg-Yelder, D.; Chen, X.; Muppa, S.; Chambers-Wilson, R.; Davis Parker, C.; Williams, J.; Polach, K.J.; Zhang, W.; Raman, K.; Babu, Y.S. Berotralstat (BCX7353): Structure-guided design of a potent, selective, and oral plasma kallikrein inhibitor to prevent attacks of hereditary angioedema (HAE). J. Med. Chem., 2021, 64(17), 12453-12468.
[http://dx.doi.org/10.1021/acs.jmedchem.1c00511] [PMID: 34436898]
[87]
Lindenbach, B.D.; Rice, C.M. Unravelling hepatitis C virus replication from genome to function. Nature, 2005, 436(7053), 933-938.
[http://dx.doi.org/10.1038/nature04077] [PMID: 16107832]
[88]
Manns, M.P.; Maasoumy, B. Breakthroughs in hepatitis C research: from discovery to cure. Nat. Rev. Gastroenterol. Hepatol., 2022, 19(8), 533-550.
[http://dx.doi.org/10.1038/s41575-022-00608-8] [PMID: 35595834]
[89]
Bogen, S.L.; Arasappan, A.; Bennett, F.; Chen, K.; Jao, E.; Liu, Y.T.; Lovey, R.G.; Venkatraman, S.; Pan, W.; Parekh, T.; Pike, R.E.; Ruan, S.; Liu, R.; Baroudy, B.; Agrawal, S.; Chase, R.; Ingravallo, P.; Pichardo, J.; Prongay, A.; Brisson, J.M.; Hsieh, T.Y.; Cheng, K.C.; Kemp, S.J.; Levy, O.E.; Lim-Wilby, M.; Tamura, S.Y.; Saksena, A.K.; Girijavallabhan, V.; Njoroge, F.G. Discovery of SCH446211 (SCH6): a new ketoamide inhibitor of the HCV NS3 serine protease and HCV subgenomic RNA replication. J. Med. Chem., 2006, 49(9), 2750-2757.
[http://dx.doi.org/10.1021/jm060077j] [PMID: 16640336]
[90]
Morrison, J.F.; Walsh, C.T. The behavior and significance of slow-binding enzyme inhibitors. In: Advances in Enzymology and Related Areas of Molecular Biology; Meister, A., Ed.; John Wiley & Sons, Ltd, 1988; pp. 201-301.
[http://dx.doi.org/10.1002/9780470123072.ch5]
[91]
Venkatraman, S.; Bogen, S.L.; Arasappan, A.; Bennett, F.; Chen, K.; Jao, E.; Liu, Y.T.; Lovey, R.; Hendrata, S.; Huang, Y.; Pan, W.; Parekh, T.; Pinto, P.; Popov, V.; Pike, R.; Ruan, S.; Santhanam, B.; Vibulbhan, B.; Wu, W.; Yang, W.; Kong, J.; Liang, X.; Wong, J.; Liu, R.; Butkiewicz, N.; Chase, R.; Hart, A.; Agrawal, S.; Ingravallo, P.; Pichardo, J.; Kong, R.; Baroudy, B.; Malcolm, B.; Guo, Z.; Prongay, A.; Madison, V.; Broske, L.; Cui, X.; Cheng, K.C.; Hsieh, Y.; Brisson, J.M.; Prelusky, D.; Korfmacher, W.; White, R.; Bogdanowich-Knipp, S.; Pavlovsky, A.; Bradley, P.; Saksena, A.K.; Ganguly, A.; Piwinski, J.; Girijavallabhan, V.; Njoroge, F.G. Discovery of (1R,5S)-N-[3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]- 3-[2(S)-[[[(1,1-dimethylethyl)amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]- 6,6-dimethyl-3-azabicyclo[3.1.0]hexan-2(S)-carboxamide (SCH 503034), a selective, potent, orally bioavailable hepatitis C virus NS3 protease inhibitor: a potential therapeutic agent for the treatment of hepatitis C infection. J. Med. Chem., 2006, 49(20), 6074-6086.
[http://dx.doi.org/10.1021/jm060325b] [PMID: 17004721]
[92]
Prongay, A.J.; Guo, Z.; Yao, N.; Pichardo, J.; Fischmann, T.; Strickland, C.; Myers, J., Jr; Weber, P.C.; Beyer, B.M.; Ingram, R.; Hong, Z.; Prosise, W.W.; Ramanathan, L.; Taremi, S.S.; Yarosh-Tomaine, T.; Zhang, R.; Senior, M.; Yang, R.S.; Malcolm, B.; Arasappan, A.; Bennett, F.; Bogen, S.L.; Chen, K.; Jao, E.; Liu, Y.T.; Lovey, R.G.; Saksena, A.K.; Venkatraman, S.; Girijavallabhan, V.; Njoroge, F.G.; Madison, V. Discovery of the HCV NS3/4A protease inhibitor (1 R, 5 S)-N -[3-Amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]-3- [2( S )-[[[(1,1-dimethylethyl)amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]- 6,6-dimethyl-3-azabicyclo[3.1.0]hexan-2( S )-carboxamide (Sch 503034) II. Key steps in structure-based optimization. J. Med. Chem., 2007, 50(10), 2310-2318.
[http://dx.doi.org/10.1021/jm060173k] [PMID: 17444623]
[93]
Bäck, M.; Johansson, P.O.; Wångsell, F.; Thorstensson, F.; Kvarnström, I.; Ayesa, S.; Wähling, H.; Pelcman, M.; Jansson, K.; Lindström, S.; Wallberg, H.; Classon, B.; Rydergård, C.; Vrang, L.; Hamelink, E.; Hallberg, A.; Rosenquist, Å.; Samuelsson, B. Novel potent macrocyclic inhibitors of the hepatitis C virus NS3 protease: Use of cyclopentane and cyclopentene P2-motifs. Bioorg. Med. Chem., 2007, 15(22), 7184-7202.
[http://dx.doi.org/10.1016/j.bmc.2007.07.027] [PMID: 17845856]
[94]
Raboisson, P.; de Kock, H.; Rosenquist, Å.; Nilsson, M.; Salvador-Oden, L.; Lin, T.I.; Roue, N.; Ivanov, V.; Wähling, H.; Wickström, K.; Hamelink, E.; Edlund, M.; Vrang, L.; Vendeville, S.; Van de Vreken, W.; McGowan, D.; Tahri, A.; Hu, L.; Boutton, C.; Lenz, O.; Delouvroy, F.; Pille, G.; Surleraux, D.; Wigerinck, P.; Samuelsson, B.; Simmen, K. Structure–activity relationship study on a novel series of cyclopentane-containing macrocyclic inhibitors of the hepatitis C virus NS3/4A protease leading to the discovery of TMC435350. Bioorg. Med. Chem. Lett., 2008, 18(17), 4853-4858.
[http://dx.doi.org/10.1016/j.bmcl.2008.07.088] [PMID: 18678486]
[95]
Rosenquist, Å.; Samuelsson, B.; Johansson, P.O.; Cummings, M.D.; Lenz, O.; Raboisson, P.; Simmen, K.; Vendeville, S.; de Kock, H.; Nilsson, M.; Horvath, A.; Kalmeijer, R.; de la Rosa, G.; Beumont-Mauviel, M. Discovery and development of simeprevir (TMC435), a HCV NS3/4A protease inhibitor. J. Med. Chem., 2014, 57(5), 1673-1693.
[http://dx.doi.org/10.1021/jm401507s] [PMID: 24446688]
[96]
Llinàs-Brunet, M.; Bailey, M.D.; Bolger, G.; Brochu, C.; Faucher, A.M.; Ferland, J.M.; Garneau, M.; Ghiro, E.; Gorys, V.; Grand-Maître, C.; Halmos, T.; Lapeyre-Paquette, N.; Liard, F.; Poirier, M.; Rhéaume, M.; Tsantrizos, Y.S.; Lamarre, D. Structure-activity study on a novel series of macrocyclic inhibitors of the hepatitis C virus NS3 protease leading to the discovery of BILN 2061. J. Med. Chem., 2004, 47(7), 1605-1608.
[http://dx.doi.org/10.1021/jm0342414] [PMID: 15027850]
[97]
Hinrichsen, H.; Benhamou, Y.; Wedemeyer, H.; Reiser, M.; Sentjens, R.E.; Calleja, J.L.; Forns, X.; Erhardt, A.; Crönlein, J.; Chaves, R.L.; Yong, C.L.; Nehmiz, G.; Steinmann, G.G. Short-term antiviral efficacy of BILN 2061, a hepatitis C virus serine protease inhibitor, in hepatitis C genotype 1 patients. Gastroenterology, 2004, 127(5), 1347-1355.
[http://dx.doi.org/10.1053/j.gastro.2004.08.002] [PMID: 15521004]
[98]
Stoltz, J.H.; Stern, J.O.; Huang, Q.; Seidler, R.W.; Pack, F.D.; Knight, B.L. A twenty-eight-day mechanistic time course study in the rhesus monkey with hepatitis C virus protease inhibitor BILN 2061. Toxicol. Pathol., 2011, 39(3), 496-501.
[http://dx.doi.org/10.1177/0192623311398276] [PMID: 21441227]
[99]
Cummings, M.D.; Lindberg, J.; Lin, T.I.; de Kock, H.; Lenz, O.; Lilja, E.; Felländer, S.; Baraznenok, V.; Nyström, S.; Nilsson, M.; Vrang, L.; Edlund, M.; Rosenquist, Å.; Samuelsson, B.; Raboisson, P.; Simmen, K. Induced-fit binding of the macrocyclic noncovalent inhibitor TMC435 to its HCV NS3/NS4A protease target. Angew. Chem. Int. Ed., 2010, 49(9), 1652-1655.
[http://dx.doi.org/10.1002/anie.200906696] [PMID: 20166108]
[100]
McPhee, F.; Sheaffer, A.K.; Friborg, J.; Hernandez, D.; Falk, P.; Zhai, G.; Levine, S.; Chaniewski, S.; Yu, F.; Barry, D.; Chen, C.; Lee, M.S.; Mosure, K.; Sun, L.Q.; Sinz, M.; Meanwell, N.A.; Colonno, R.J.; Knipe, J.; Scola, P. Preclinical profile and characterization of the hepatitis C virus NS3 protease inhibitor asunaprevir (BMS-650032). Antimicrob. Agents Chemother., 2012, 56(10), 5387-5396.
[http://dx.doi.org/10.1128/AAC.01186-12] [PMID: 22869577]
[101]
Scola, P.M.; Sun, L.Q.; Wang, A.X.; Chen, J.; Sin, N.; Venables, B.L.; Sit, S.Y.; Chen, Y.; Cocuzza, A.; Bilder, D.M.; D’Andrea, S.V.; Zheng, B.; Hewawasam, P.; Tu, Y.; Friborg, J.; Falk, P.; Hernandez, D.; Levine, S.; Chen, C.; Yu, F.; Sheaffer, A.K.; Zhai, G.; Barry, D.; Knipe, J.O.; Han, Y.H.; Schartman, R.; Donoso, M.; Mosure, K.; Sinz, M.W.; Zvyaga, T.; Good, A.C.; Rajamani, R.; Kish, K.; Tredup, J.; Klei, H.E.; Gao, Q.; Mueller, L.; Colonno, R.J.; Grasela, D.M.; Adams, S.P.; Loy, J.; Levesque, P.C.; Sun, H.; Shi, H.; Sun, L.; Warner, W.; Li, D.; Zhu, J.; Meanwell, N.A.; McPhee, F. The discovery of asunaprevir (BMS-650032), an orally efficacious NS3 protease inhibitor for the treatment of hepatitis C virus infection. J. Med. Chem., 2014, 57(5), 1730-1752.
[http://dx.doi.org/10.1021/jm500297k] [PMID: 24564672]
[102]
Scola, P.M.; Wang, A.X.; Good, A.C.; Sun, L.Q.; Combrink, K.D.; Campbell, J.A.; Chen, J.; Tu, Y.; Sin, N.; Venables, B.L.; Sit, S.Y.; Chen, Y.; Cocuzza, A.; Bilder, D.M.; D’Andrea, S.; Zheng, B.; Hewawasam, P.; Ding, M.; Thuring, J.; Li, J.; Hernandez, D.; Yu, F.; Falk, P.; Zhai, G.; Sheaffer, A.K.; Chen, C.; Lee, M.S.; Barry, D.; Knipe, J.O.; Li, W.; Han, Y.H.; Jenkins, S.; Gesenberg, C.; Gao, Q.; Sinz, M.W.; Santone, K.S.; Zvyaga, T.; Rajamani, R.; Klei, H.E.; Colonno, R.J.; Grasela, D.M.; Hughes, E.; Chien, C.; Adams, S.; Levesque, P.C.; Li, D.; Zhu, J.; Meanwell, N.A.; McPhee, F. Discovery and early clinical evaluation of BMS-605339, a potent and orally efficacious tripeptidic acylsulfonamide NS3 protease inhibitor for the treatment of hepatitis C virus infection. J. Med. Chem., 2014, 57(5), 1708-1729.
[http://dx.doi.org/10.1021/jm401840s] [PMID: 24555570]
[103]
Soumana, D.I.; Ali, A.; Schiffer, C.A. Structural analysis of asunaprevir resistance in HCV NS3/4A protease. ACS Chem. Biol., 2014, 9(11), 2485-2490.
[http://dx.doi.org/10.1021/cb5006118] [PMID: 25243902]
[104]
Gower, E.; Estes, C.; Blach, S.; Razavi-Shearer, K.; Razavi, H. Global epidemiology and genotype distribution of the hepatitis C virus infection. J. Hepatol., 2014, 61(1)(Suppl.), S45-S57.
[http://dx.doi.org/10.1016/j.jhep.2014.07.027] [PMID: 25086286]
[105]
Messina, J.P.; Humphreys, I.; Flaxman, A.; Brown, A.; Cooke, G.S.; Pybus, O.G.; Barnes, E. Global distribution and prevalence of hepatitis C virus genotypes. Hepatology, 2015, 61(1), 77-87.
[http://dx.doi.org/10.1002/hep.27259] [PMID: 25069599]
[106]
Soumana, D.I.; Kurt Yilmaz, N.; Ali, A.; Prachanronarong, K.L.; Schiffer, C.A. molecular and dynamic mechanism underlying drug resistance in genotype 3 hepatitis C NS3/4A protease. J. Am. Chem. Soc., 2016, 138(36), 11850-11859.
[http://dx.doi.org/10.1021/jacs.6b06454] [PMID: 27512818]
[107]
Mishra, P.; Chen, M. Direct-acting antivirals for chronic hepatitis C: Can drug properties signal potential for liver injury? Gastroenterology, 2017, 152(6), 1270-1274.
[http://dx.doi.org/10.1053/j.gastro.2017.03.012] [PMID: 28327365]
[108]
Harper, S.; McCauley, J.A.; Rudd, M.T.; Ferrara, M.; DiFilippo, M.; Crescenzi, B.; Koch, U.; Petrocchi, A.; Holloway, M.K.; Butcher, J.W.; Romano, J.J.; Bush, K.J.; Gilbert, K.F.; McIntyre, C.J.; Nguyen, K.T.; Nizi, E.; Carroll, S.S.; Ludmerer, S.W.; Burlein, C.; DiMuzio, J.M.; Graham, D.J.; McHale, C.M.; Stahlhut, M.W.; Olsen, D.B.; Monteagudo, E.; Cianetti, S.; Giuliano, C.; Pucci, V.; Trainor, N.; Fandozzi, C.M.; Rowley, M.; Coleman, P.J.; Vacca, J.P.; Summa, V.; Liverton, N.J. Discovery of MK-5172, a macrocyclic hepatitis C virus NS3/4a protease inhibitor. ACS Med. Chem. Lett., 2012, 3(4), 332-336.
[http://dx.doi.org/10.1021/ml300017p] [PMID: 24900473]
[109]
Taylor, J.G.; Zipfel, S.; Ramey, K.; Vivian, R.; Schrier, A.; Karki, K.K.; Katana, A.; Kato, D.; Kobayashi, T.; Martinez, R.; Sangi, M.; Siegel, D.; Tran, C.V.; Yang, Z.Y.; Zablocki, J.; Yang, C.Y.; Wang, Y.; Wang, K.; Chan, K.; Barauskas, O.; Cheng, G.; Jin, D.; Schultz, B.E.; Appleby, T.; Villaseñor, A.G.; Link, J.O. Discovery of the pan-genotypic hepatitis C virus NS3/4A protease inhibitor voxilaprevir (GS-9857): A component of Vosevi®. Bioorg. Med. Chem. Lett., 2019, 29(16), 2428-2436.
[http://dx.doi.org/10.1016/j.bmcl.2019.03.037] [PMID: 31133531]
[110]
Taylor, J.G. Discovery of voxilaprevir (GS-9857): The pan-genotypic hepatitis C virus NS3/4A protease inhibitor utilized as a component of Vosevi®. In: In HCV: The Journey from Discovery to a Cure; Sofia, M. Springer International Publishing, 2019; pp. 441-457.
[http://dx.doi.org/10.1007/7355_2018_61]
[111]
Romano, K.P.; Ali, A.; Aydin, C.; Soumana, D.; Özen, A.; Deveau, L.M.; Silver, C.; Cao, H.; Newton, A.; Petropoulos, C.J.; Huang, W.; Schiffer, C.A. The molecular basis of drug resistance against hepatitis C virus NS3/4A protease inhibitors. PLoS Pathog., 2012, 8(7), e1002832.
[http://dx.doi.org/10.1371/journal.ppat.1002832] [PMID: 22910833]
[112]
Tujios, S.; Fontana, R.J. Mechanisms of drug-induced liver injury: from bedside to bench. Nat. Rev. Gastroenterol. Hepatol., 2011, 8(4), 202-211.
[http://dx.doi.org/10.1038/nrgastro.2011.22] [PMID: 21386809]
[113]
Norman, B.H. Drug induced liver injury (DILI). Mechanisms and medicinal chemistry avoidance/mitigation strategies. J. Med. Chem., 2020, 63(20), 11397-11419.
[http://dx.doi.org/10.1021/acs.jmedchem.0c00524] [PMID: 32511920]
[114]
Kumari, S.; Carmona, A.V.; Tiwari, A.K.; Trippier, P.C. Amide bond bioisosteres: Strategies, synthesis, and successes. J. Med. Chem., 2020, 63(21), 12290-12358.
[http://dx.doi.org/10.1021/acs.jmedchem.0c00530] [PMID: 32686940]
[115]
Vitaku, E.; Smith, D.T.; Njardarson, J.T. Analysis of the structural diversity, substitution patterns, and frequency of nitrogen heterocycles among U.S. FDA approved pharmaceuticals. J. Med. Chem., 2014, 57(24), 10257-10274.
[http://dx.doi.org/10.1021/jm501100b] [PMID: 25255204]
[116]
Delost, M.D.; Smith, D.T.; Anderson, B.J.; Njardarson, J.T. From oxiranes to oligomers: Architectures of U.S. FDA approved pharmaceuticals containing oxygen heterocycles. J. Med. Chem., 2018, 61(24), 10996-11020.
[http://dx.doi.org/10.1021/acs.jmedchem.8b00876] [PMID: 30024747]
[117]
St Jean, D.J., Jr; Fotsch, C. Mitigating heterocycle metabolism in drug discovery. J. Med. Chem., 2012, 55(13), 6002-6020.
[http://dx.doi.org/10.1021/jm300343m] [PMID: 22533875]
[118]
Pennington, L.D.; Moustakas, D.T. The necessary nitrogen atom: A versatile high-impact design element for multiparameter optimization. J. Med. Chem., 2017, 60(9), 3552-3579.
[http://dx.doi.org/10.1021/acs.jmedchem.6b01807] [PMID: 28177632]
[119]
Peterlin Masic, L. Arginine mimetic structures in biologically active antagonists and inhibitors. Curr. Med. Chem., 2006, 13(30), 3627-3648.
[http://dx.doi.org/10.2174/092986706779026101] [PMID: 17168727]
[120]
Meanwell, N.A. The influence of bioisosteres in drug design: Tactical applications to address developability problems.Tactics in Contemporary Drug Design; Meanwell, N.A., Ed.; Springer, 2015, pp. 283-381.
[http://dx.doi.org/10.1007/978-3-642-55041-6]

Rights & Permissions Print Cite
Article Metrics
38
2
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy