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Review Article

结构活性关系视角下的凝血酶抑制剂综述

卷 30, 期 25, 2023

发表于: 07 November, 2022

页: [2864 - 2930] 页: 67

弟呕挨: 10.2174/0929867329666220906105200

价格: $65

Open Access Journals Promotions 2
摘要

血栓形成是与心血管疾病有关的最重要的致病因素之一。目前，凝血酶抑制剂因其独特的潜力，如达比加群，在临床实践中逐渐获得突出地位。然而，出血的风险并没有完全消除，在某些情况下，胃肠道出血的威胁甚至增加。因此，迫切需要开发副作用低的新型口服凝血酶抑制剂。本文综合论述了2000—2019年新合成分离的凝血酶抑制剂及其构效关系（SARs）及其结构依赖性药代动力学参数的研究进展，为下一代口服凝血酶抑制剂提供了指导。

关键词: 抗血栓药，凝血酶抑制剂，构效关系，药代动力学。

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[1]
Benjamin, E.J.; Virani, S.S.; Callaway, C.W.; Chamberlain, A.M.; Chang, A.R.; Cheng, S.; Chiuve, S.E.; Cushman, M.; Delling, F.N.; Deo, R.; de Ferranti, S.D.; Ferguson, J.F.; Fornage, M.; Gillespie, C.; Isasi, C.R.; Jiménez, M.C.; Jordan, L.C.; Judd, S.E.; Lackland, D.; Lichtman, J.H.; Lisabeth, L.; Liu, S.; Longenecker, C.T.; Lutsey, P.L.; Mackey, J.S.; Matchar, D.B.; Matsushita, K.; Mussolino, M.E.; Nasir, K.; O’Flaherty, M.; Palaniappan, L.P.; Pandey, A.; Pandey, D.K.; Reeves, M.J.; Ritchey, M.D.; Rodriguez, C.J.; Roth, G.A.; Rosamond, W.D.; Sampson, U.K.A.; Satou, G.M.; Shah, S.H.; Spartano, N.L.; Tirschwell, D.L.; Tsao, C.W.; Voeks, J.H.; Willey, J.Z.; Wilkins, J.T.; Wu, J.H.; Alger, H.M.; Wong, S.S.; Muntner, P. Heart disease and stroke statistics-2018 Update: A report from the American Heart Association. Circulation, 2018, 137(12), e67-e492.
[http://dx.doi.org/10.1161/CIR.0000000000000558] [PMID: 29386200]
[2]
Quan, M.L.; Pinto, D.J.P.; Smallheer, J.M.; Ewing, W.R.; Rossi, K.A.; Luettgen, J.M.; Seiffert, D.A.; Wexler, R.R. Factor XIa inhibitors as new anticoagulants. J. Med. Chem., 2021, 61(17), 7425-7447.
[http://dx.doi.org/10.1021/acs.jmedchem.8b00173] [PMID: 29775297];
(2a) Wang, Y.; Chen, H.; Sheng, R.; Fu, Z.; Fan, J.; Wu, W.; Tu, Q.; Guo, R. Synthesis and bioactivities of marine pyran-isoindolone derivatives as potential antithrombotic agents. Mar. Drugs, 2021, 19(4), 218.
[http://dx.doi.org/10.3390/md19040218] [PMID: 33921137]
[3]
World Health Organization. World Health Statistics. Monitoring Health for the SDGs, Sustainable Development Goals; World Health Organization: Genève, 2018.
[4]
Li, H.; Ge, J. Cardiovascular diseases in China: Current status and future perspectives. Int. J. Cardiol. Heart Vasc., 2014, 6, 25-31.
[http://dx.doi.org/10.1016/j.ijcha.2014.10.002] [PMID: 28785622]
[5]
Valavanidis, A.; Fiotakis, K.; Vlachogianni, T. Airborne particulate matter and human health: Toxicological assessment and importance of size and composition of particles for oxidative damage and carcinogenic mechanisms. J. Environ. Sci. Health Part C Environ. Carcinog. Ecotoxicol. Rev., 2008, 26(4), 339-362.
[http://dx.doi.org/10.1080/10590500802494538] [PMID: 19034792]
[6]
Wendelboe, A.M.; Raskob, G.E. Global burden of thrombosis: Epidemiologic aspects. Circ. Res., 2016, 118(9), 1340-1347.
[http://dx.doi.org/10.1161/CIRCRESAHA.115.306841] [PMID: 27126645]
[7]
Steg, P.G.; James, S.K.; Atar, D.; Badano, L.P.; Blömstrom-Lundqvist, C.; Borger, M.A.; Di Mario, C.; Dickstein, K.; Ducrocq, G.; Fernandez-Aviles, F.; Gershlick, A.H.; Giannuzzi, P.; Halvorsen, S.; Huber, K.; Juni, P.; Kastrati, A.; Knuuti, J.; Lenzen, M.J.; Mahaffey, K.W.; Valgimigli, M.; van ’t Hof, A.; Widimsky, P.; Zahger, D. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur. Heart J., 2012, 33(20), 2569-2619.
[http://dx.doi.org/10.1093/eurheartj/ehs215] [PMID: 22922416]
[8]
Morrow, D.A.; Wiviott, S.D.; White, H.D.; Nicolau, J.C.; Bramucci, E.; Murphy, S.A.; Bonaca, M.P.; Ruff, C.T.; Scirica, B.M.; McCabe, C.H.; Antman, E.M.; Braunwald, E. Effect of the novel thienopyridine prasugrel compared with clopidogrel on spontaneous and procedural myocardial infarction in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis in Myocardial Infarction 38: An application of the classification system from the universal definition of myocardial infarction. Circulation, 2009, 119(21), 2758-2764.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.108.833665] [PMID: 19451347]
[9]
Kapoor, J.R. Platelet activation and atherothrombosis. N. Engl. J. Med., 2008, 358(15), 1638-1639.
[http://dx.doi.org/10.1056/NEJMc080056] [PMID: 18403776]
[10]
Ossovskaya, V.S.; Bunnett, N.W. Protease-activated receptors: Contribution to physiology and disease. Physiol. Rev., 2004, 84(2), 579-621.
[http://dx.doi.org/10.1152/physrev.00028.2003] [PMID: 15044683]
[11]
Mackman, N. Triggers, targets and treatments for thrombosis. Nature, 2008, 451(7181), 914-918.
[http://dx.doi.org/10.1038/nature06797] [PMID: 18288180]
[12]
Popov Aleksandrov, A.; Mirkov, I.; Ninkov, M.; Mileusnic, D.; Demenesku, J.; Subota, V.; Kataranovski, D.; Kataranovski, M. Effects of warfarin on biological processes other than haemostasis: A review. Food Chem. Toxicol., 2018, 113, 19-32.
[http://dx.doi.org/10.1016/j.fct.2018.01.019] [PMID: 29353071]
[13]
Harenberg, J.; Marx, S.; Krejczy, M.; Wehling, M. New anticoagulants - promising and failed developments. Br. J. Pharmacol., 2012, 165(2), 363-372.
[http://dx.doi.org/10.1111/j.1476-5381.2011.01578.x] [PMID: 21740405]
[14]
Kong, Y.; Chen, H.; Wang, Y-Q.; Meng, L.; Wei, J-F. Direct thrombin inhibitors: Patents 2002-2012. Mol. Med. Rep., 2014, 9, 1506-1514.
[15]
Yeh, C.H.; Hogg, K.; Weitz, J.I. Overview of the new oral anticoagulants: Opportunities and challenges. Arterioscler. Thromb. Vasc. Biol., 2015, 35(5), 1056-1065.
[http://dx.doi.org/10.1161/ATVBAHA.115.303397] [PMID: 25792448]
[16]
Ruff, C.T.; Giugliano, R.P.; Braunwald, E.; Hoffman, E.B.; Deenadayalu, N.; Ezekowitz, M.D.; Camm, A.J.; Weitz, J.I.; Lewis, B.S.; Parkhomenko, A.; Yamashita, T.; Antman, E.M. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: A meta-analysis of randomised trials. Lancet, 2014, 383(9921), 955-962.
[http://dx.doi.org/10.1016/S0140-6736(13)62343-0] [PMID: 24315724]
[17]
McNamara, C.A.; Sarembock, I.J.; Gimple, L.W.; Fenton, J.W.D., II; Coughlin, S.R.; Owens, G.K. Thrombin stimulates proliferation of cultured rat aortic smooth muscle cells by a proteolytically activated receptor. J. Clin. Invest., 1993, 91(1), 94-98.
[http://dx.doi.org/10.1172/JCI116206] [PMID: 8380817]
[18]
Mhatre, M.; Nguyen, A.; Kashani, S.; Pham, T.; Adesina, A.; Grammas, P. Thrombin, a mediator of neurotoxicity and memory impairment. Neurobiol. Aging, 2004, 25(6), 783-793.
[http://dx.doi.org/10.1016/j.neurobiolaging.2003.07.007] [PMID: 15165703]
[19]
Gould, T.W.; Dominguez, B.; de Winter, F.; Yeo, G.W.; Liu, P.; Sundararaman, B.; Stark, T.; Vu, A.; Degen, J.L.; Lin, W.; Lee, K.F. Glial cells maintain synapses by inhibiting an activity-dependent retrograde protease signal. PLoS Genet., 2019, 15(3), e1007948.
[http://dx.doi.org/10.1371/journal.pgen.1007948] [PMID: 30870413]
[20]
Warkentin, T.E. Bivalent direct thrombin inhibitors: Hirudin and bivalirudin. Best Pract. Res. Clin. Haematol., 2004, 17(1), 105-125.
[http://dx.doi.org/10.1016/j.beha.2004.02.002] [PMID: 15171961]
[21]
Hankey, G.J.; Eikelboom, J.W. Dabigatran etexilate: A new oral thrombin inhibitor. Circulation, 2011, 123(13), 1436-1450.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.110.004424] [PMID: 21464059]
[22]
Nutescu, E.A.; Wittkowsky, A.K. Direct thrombin inhibitors for anticoagulation. Ann. Pharmacother., 2004, 38(1), 99-109.
[http://dx.doi.org/10.1345/aph.1D066] [PMID: 14742803]
[23]
Lee, C.J.; Ansell, J.E. Direct thrombin inhibitors. Br. J. Clin. Pharmacol., 2011, 72(4), 581-592.
[http://dx.doi.org/10.1111/j.1365-2125.2011.03916.x] [PMID: 21241354]
[24]
Kam, P.C.A.; Kaur, N.; Thong, C.L. Direct thrombin inhibitors: Pharmacology and clinical relevance. Anaesthesia, 2005, 60(6), 565-574.
[http://dx.doi.org/10.1111/j.1365-2044.2005.04192.x] [PMID: 15918828]
[25]
de Moerloose, P.; Boehlen, F. Two new antithrombotic agents (fondaparinux and ximelagatran) and their implications in anesthesia. Can. J. Anaesth., 2002, 49(6), S5-S10.
[PMID: 12557410]
[26]
Das, J.; Kimball, S.D. Thrombin active site inhibitors. Bioorg. Med. Chem., 1995, 3(8), 999-1007.
[http://dx.doi.org/10.1016/0968-0896(95)00104-O] [PMID: 7582987]
[27]
Steinmetzer, T.; Stürzebecher, J. Progress in the development of synthetic thrombin inhibitors as new orally active anticoagulants. Curr. Med. Chem., 2004, 11(17), 2297-2321.
[http://dx.doi.org/10.2174/0929867043364540] [PMID: 15379714]
[28]
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. Engl., 2011, 50(20), 4574-4590.
[http://dx.doi.org/10.1002/anie.201004575] [PMID: 21538731]
[29]
Mehta, A.Y.; Jin, Y.; Desai, U.R. An update on recent patents on thrombin inhibitors (2010 - 2013). Expert Opin. Ther. Pat., 2014, 24(1), 47-67.
[http://dx.doi.org/10.1517/13543776.2014.845169] [PMID: 24099091]
[30]
He, L.W.; Dai, W.C.; Li, N.G. Development of orally active thrombin inhibitors for the treatment of thrombotic disorder diseases. Molecules, 2015, 20(6), 11046-11062.
[http://dx.doi.org/10.3390/molecules200611046] [PMID: 26083038]
[31]
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]
[32]
Zhu, D. The composition and function of blood. In: Human anatomy and physiology, 7th Ed; Zhou, H.; Cui, H., Eds.; People’s Medical Publishing House: Beijing, 2017; p. 75.
[33]
Rachel, B.S. Protease-activated receptors. In: Encyclopedia of Cancer; Schwab, M., Ed.; Springer Berlin Heidelberg: Berlin, Heidelberg, 2015; pp. 1-4.
[34]
Kahn, M.L.; Nakanishi-Matsui, M.; Shapiro, M.J.; Ishihara, H.; Coughlin, S.R. Protease-activated receptors 1 and 4 mediate activation of human platelets by thrombin. J. Clin. Invest., 1999, 103(6), 879-887.
[http://dx.doi.org/10.1172/JCI6042] [PMID: 10079109]
[35]
Antoniak, S.; Pawlinski, R.; Mackman, N. Protease-activated receptors and myocardial infarction. IUBMB Life, 2011, 63(6), 383-389.
[http://dx.doi.org/10.1002/iub.441] [PMID: 21438116]
[36]
Coughlin, S.R. Thrombin signalling and protease-activated receptors. Nature, 2000, 407(6801), 258-264.
[http://dx.doi.org/10.1038/35025229] [PMID: 11001069]
[37]
Vu, T.K.H.; Wheaton, V.I.; Hung, D.T.; Charo, I.; Coughlin, S.R. Domains specifying thrombin-receptor interaction. Nature, 1991, 353(6345), 674-677.
[http://dx.doi.org/10.1038/353674a0] [PMID: 1717851]
[38]
Aslan, J.E. Platelet Rho GTPase regulation in physiology and disease. Platelets, 2019, 30(1), 17-22.
[http://dx.doi.org/10.1080/09537104.2018.1475632] [PMID: 29799302]
[39]
Angiolillo, D.J.; Ueno, M. Optimizing platelet inhibition in clopidogrel poor metabolizers: Therapeutic options and practical considerations. JACC Cardiovasc. Interv., 2011, 4(4), 411-414.
[http://dx.doi.org/10.1016/j.jcin.2011.03.001] [PMID: 21511220]
[40]
Stenberg, P.E.; McEver, R.P.; Shuman, M.A.; Jacques, Y.V.; Bainton, D.F. A platelet alpha-granule membrane protein (GMP-140) is expressed on the plasma membrane after activation. J. Cell Biol., 1985, 101(3), 880-886.
[http://dx.doi.org/10.1083/jcb.101.3.880] [PMID: 2411738]
[41]
Henn, V.; Slupsky, J.R.; Gräfe, M.; Anagnostopoulos, I.; Förster, R.; Müller-Berghaus, G.; Kroczek, R.A. CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells. Nature, 1998, 391(6667), 591-594.
[http://dx.doi.org/10.1038/35393] [PMID: 9468137]
[42]
Rohde, M.; Mayer, F.; Hicks, D.B.; Krulwich, T.A. Immunoelectron microscopic localization of the F1F0 ATPase (ATP synthase) on the cytoplasmic membrane of alkalophilic Bacillus firmus RAB. Biomembranes, 1989, 985, 233-235.
[43]
Angiolillo, D.J.; Capodanno, D.; Goto, S. Platelet thrombin receptor antagonism and atherothrombosis. Eur. Heart J., 2010, 31(1), 17-28.
[http://dx.doi.org/10.1093/eurheartj/ehp504] [PMID: 19948715]
[44]
Chen, Z.; Seiffert, D.; Hawes, B. Inhibition of Factor XI activity as a promising antithrombotic strategy. Drug Discov. Today, 2014, 19(9), 1435-1439.
[http://dx.doi.org/10.1016/j.drudis.2014.04.018] [PMID: 24794465]
[45]
Al-Horani, R.A.; Desai, U.R. Factor XIa inhibitors: A review of the patent literature. Expert Opin. Ther. Pat., 2016, 26(3), 323-345.
[http://dx.doi.org/10.1517/13543776.2016.1154045] [PMID: 26881476]
[46]
Bane, C.E., Jr; Gailani, D. Factor XI as a target for antithrombotic therapy. Drug Discov. Today, 2014, 19(9), 1454-1458.
[http://dx.doi.org/10.1016/j.drudis.2014.05.018] [PMID: 24886766]
[47]
Lee, Y.K.; Player, M.R. Developments in factor Xa inhibitors for the treatment of thromboembolic disorders. Med. Res. Rev., 2011, 31(2), 202-283.
[http://dx.doi.org/10.1002/med.20183] [PMID: 19967784]
[48]
(a) Al-Horani, R.A.; Afosah, D.K. Recent advances in the discovery and development of factor XI/XIa inhibitors. Med. Res. Rev., 2018, 38(6), 1974-2023.
[http://dx.doi.org/10.1002/med.21503] [PMID: 29727017]
[49]
Wood, J.P.; Ellery, P.E.R.; Maroney, S.A.; Mast, A.E. Biology of tissue factor pathway inhibitor. Blood, 2014, 123(19), 2934-2943.
[http://dx.doi.org/10.1182/blood-2013-11-512764] [PMID: 24620349];
(b) Guo, R.; Duan, D.; Hong, S.; Zhou, Y.; Wang, F.; Wang, S.; Wu, W.; Bao, B. A marine fibrinolytic compound FGFC1 stimulating enzymatic kinetic parameters of a reciprocal activation system based on a single chain urokinasetype plasminogen activator and plasminogen. Process Biochem., 2018, 68, 190-196.
[http://dx.doi.org/10.1016/j.procbio.2018.01.024];
(c) Guo, R.; Zhang, Y.; Duan, D.; Fu, Q.; Zhang, X.; Yu, X.; Wang, S.; Bao, B.; Wu, W. Fibrinolytic evaluation of compounds isolated from a marine fungus stachybotrys longispora FG216. Chin. J. Chem., 2016, 34, 1194-1198.
[http://dx.doi.org/10.1002/cjoc.201600623]
[50]
Griffin, J.H.; Fernández, J.A.; Gale, A.J.; Mosnier, L.O. Activated protein C. J. Thromb. Haemost., 2007, 5(Suppl. 1), 73-80.
[http://dx.doi.org/10.1111/j.1538-7836.2007.02491.x] [PMID: 17635713]
[51]
Corral, J.; de la Morena-Barrio, M.E.; Vicente, V. The genetics of antithrombin. Thromb. Res., 2018, 169, 23-29.
[http://dx.doi.org/10.1016/j.thromres.2018.07.008] [PMID: 30005274]
[52]
Gladysz, R.; Adriaenssens, Y.; De Winter, H.; Joossens, J.; Lambeir, A.M.; Augustyns, K.; Van der Veken, P. Discovery and SAR of novel and selective inhibitors of urokinase plasminogen activator (uPA) with an imidazo[1,2-a]pyridine scaffold. J. Med. Chem., 2015, 58(23), 9238-9257.
[http://dx.doi.org/10.1021/acs.jmedchem.5b01171] [PMID: 26575094]
[53]
De Nanteuil, G.; Lila-Ambroise, C.; Rupin, A.; Vallez, M.O.; Verbeuren, T.J. New fibrinolytic agents: Benzothiophene derivatives as inhibitors of the t-PA-PAI-1 complex formation. Bioorg. Med. Chem. Lett., 2003, 13(10), 1705-1708.
[http://dx.doi.org/10.1016/S0960-894X(03)00233-6] [PMID: 12729646]
[54]
Esmon, C.T. Regulation of blood coagulation. Protein Struct. M, 2000, 1477, 349-360.
[55]
Krishnaswamy, S. The transition of prothrombin to thrombin. J. Thromb. Haemost., 2013, 11(Suppl. 1), 265-276.
[http://dx.doi.org/10.1111/jth.12217] [PMID: 23809130]
[56]
Boissel, J.P.; Le Bonniec, B.; Rabiet, M.J.; Labie, D.; Elion, J. Covalent structures of beta and gamma autolytic derivatives of human alpha-thrombin. J. Biol. Chem., 1984, 259(9), 5691-5697.
[http://dx.doi.org/10.1016/S0021-9258(18)91069-0] [PMID: 6715366]
[57]
De Cristofaro, R.; Akhavan, S.; Altomare, C.; Carotti, A.; Peyvandi, F.; Mannucci, P.M. A natural prothrombin mutant reveals an unexpected influence of A-chain structure on the activity of human alpha-thrombin. J. Biol. Chem., 2004, 279(13), 13035-13043.
[http://dx.doi.org/10.1074/jbc.M312430200] [PMID: 14722067]
[58]
Bode, W.; Mayr, I.; Baumann, U.; Huber, R.; Stone, S.R.; Hofsteenge, J. The refined 1.9 A crystal structure of human α-thrombin: Interaction with D-Phe-Pro-Arg chloromethylketone and significance of the Tyr-Pro-Pro-Trp insertion segment. EMBO J., 1989, 8(11), 3467-3475.
[http://dx.doi.org/10.1002/j.1460-2075.1989.tb08511.x] [PMID: 2583108]
[59]
Singh, R.R.; Chang, J.Y. Structural stability of human α-thrombin studied by disulfide reduction and scrambling. Proteins Proteom., 2003, 1651, 85-92.
[60]
Warshel, A.; Naray-Szabo, G.; Sussman, F.; Hwang, J.K. How do serine proteases really work? Biochemistry, 1989, 28(9), 3629-3637.
[http://dx.doi.org/10.1021/bi00435a001] [PMID: 2665806]
[61]
Di Cera, E.; Dang, Q.D.; Ayala, Y.M. Molecular mechanisms of thrombin function. Cell. Mol. Life Sci., 1997, 53(9), 701-730.
[http://dx.doi.org/10.1007/s000180050091] [PMID: 9368668]
[62]
Cera, E.D.; Gruber, A. Thrombin: Structure, functions, and regulation. In: Thrombin; Maragoudakis, M.E.; Tsopanoglou, N.E., Eds.; Springer New York: New York, NY, 2009.
[http://dx.doi.org/10.1007/978-0-387-09637-7_1]
[63]
Srivastava, S.; Goswami, L.N.; Dikshit, D.K. Progress in the design of low molecular weight thrombin inhibitors. Med. Res. Rev., 2005, 25(1), 66-92.
[http://dx.doi.org/10.1002/med.20016] [PMID: 15389730]
[64]
Nar, H. The role of structural information in the discovery of direct thrombin and factor Xa inhibitors. Trends Pharmacol. Sci., 2012, 33(5), 279-288.
[http://dx.doi.org/10.1016/j.tips.2012.03.004] [PMID: 22503439]
[65]
Bhunia, S.S.; Roy, K.K.; Saxena, A.K. Profiling the structural determinants for the selectivity of representative factor-Xa and thrombin inhibitors using combined ligand-based and structure-based approaches. J. Chem. Inf. Model., 2011, 51(8), 1966-1985.
[http://dx.doi.org/10.1021/ci200185q] [PMID: 21761917]
[66]
Schiele, F.; van Ryn, J.; Canada, K.; Newsome, C.; Sepulveda, E.; Park, J.; Nar, H.; Litzenburger, T. A specific antidote for dabigatran: Functional and structural characterization. Blood, 2013, 121(18), 3554-3562.
[http://dx.doi.org/10.1182/blood-2012-11-468207] [PMID: 23476049]
[67]
Sinauridze, E.I.; Romanov, A.N.; Gribkova, I.V.; Kondakova, O.A.; Surov, S.S.; Gorbatenko, A.S.; Butylin, A.A.; Monakov, M.Y.; Bogolyubov, A.A.; Kuznetsov, Y.V.; Sulimov, V.B.; Ataullakhanov, F.I. New synthetic thrombin inhibitors: Molecular design and experimental verification. PLoS One, 2011, 6(5), e19969.
[http://dx.doi.org/10.1371/journal.pone.0019969] [PMID: 21603576]
[68]
Gandhi, P.S.; Chen, Z.; Mathews, F.S.; Di Cera, E. Structural identification of the pathway of long-range communication in an allosteric enzyme. Proc. Natl. Acad. Sci. USA, 2008, 105(6), 1832-1837.
[http://dx.doi.org/10.1073/pnas.0710894105] [PMID: 18250335]
[69]
Myles, T.; Yun, T.H.; Leung, L.L.K. Structural requirements for the activation of human factor VIII by thrombin. Blood, 2002, 100(8), 2820-2826.
[http://dx.doi.org/10.1182/blood-2002-03-0843] [PMID: 12351390]
[70]
De Filippis, V.; Quarzago, D.; Vindigni, A.; Di Cera, E.; Fontana, A. Synthesis and characterization of more potent analogues of hirudin fragment 1-47 containing non-natural amino acids. Biochemistry, 1998, 37(39), 13507-13515.
[http://dx.doi.org/10.1021/bi980717n] [PMID: 9753436]
[71]
De Filippis, V.; Acquasaliente, L.; Pontarollo, G.; Peterle, D. Noncoded amino acids in protein engineering: Structure-activity relationship studies of hirudin-thrombin interaction. Biotechnol. Appl. Biochem., 2018, 65(1), 69-80.
[http://dx.doi.org/10.1002/bab.1632] [PMID: 29230873]
[72]
Lesk, A.M.; Fordham, W.D. Conservation and variability in the structures of serine proteinases of the chymotrypsin family. J. Mol. Biol., 1996, 258(3), 501-537.
[http://dx.doi.org/10.1006/jmbi.1996.0264] [PMID: 8642605]
[73]
Srinivasan, J.; Hu, S.; Hrabal, R.; Zhu, Y.; Komives, E.A.; Ni, F. Thrombin-bound structure of an EGF subdomain from human thrombomodulin determined by transferred nuclear Overhauser effects. Biochemistry, 1994, 33(46), 13553-13560.
[http://dx.doi.org/10.1021/bi00250a007] [PMID: 7947766]
[74]
Abdel Aziz, M.H.; Desai, U.R. Novel heparin mimetics reveal cooperativity between exosite 2 and sodium-binding site of thrombin. Thromb. Res., 2018, 165, 61-67.
[http://dx.doi.org/10.1016/j.thromres.2018.03.013] [PMID: 29573721]
[75]
Lechtenberg, B.C.; Freund, S.M.V.; Huntington, J.A. GpIbα interacts exclusively with exosite II of thrombin. J. Mol. Biol., 2014, 426(4), 881-893.
[http://dx.doi.org/10.1016/j.jmb.2013.11.027] [PMID: 24316004]
[76]
Uliana, F.; Vizovišek, M.; Acquasaliente, L.; Ciuffa, R.; Fossati, A.; Frommelt, F.; Goetze, S.; Wollscheid, B.; Gstaiger, M.; De Filippis, V.; Auf dem Keller, U.; Aebersold, R. Mapping specificity, cleavage entropy, allosteric changes and substrates of blood proteases in a high-throughput screen. Nat. Commun., 2021, 12(1), 1693.
[http://dx.doi.org/10.1038/s41467-021-21754-8] [PMID: 33727531]
[77]
Huntington, J.A. How Na+ activates thrombin--a review of the functional and structural data. Biol. Chem., 2008, 389(8), 1025-1035.
[http://dx.doi.org/10.1515/BC.2008.113] [PMID: 18979627]
[78]
Xiao, J.; Salsbury, F.R. Na+-binding modes involved in thrombin’s allosteric response as revealed by molecular dynamics simulations, correlation networks and Markov modeling. Phys. Chem. Chem. Phys., 2019, 21(8), 4320-4330.
[http://dx.doi.org/10.1039/C8CP07293K] [PMID: 30724273]
[79]
von Matt, A.; Ehrhardt, C.; Burkhard, P.; Metternich, R.; Walkinshaw, M.; Tapparelli, C. Selective boron-containing thrombin inhibitors--X-ray analysis reveals surprising binding mode. Bioorg. Med. Chem., 2000, 8(9), 2291-2303.
[http://dx.doi.org/10.1016/S0968-0896(00)00147-4] [PMID: 11026541]
[80]
Wienand, A.; Ehrhardt, C.; Metternich, R.; Tapparelli, C. Design, synthesis and biological evaluation of selective boron-containing thrombin inhibitors. Bioorg. Med. Chem., 1999, 7(7), 1295-1307.
[http://dx.doi.org/10.1016/S0968-0896(99)00069-3] [PMID: 10465405]
[81]
Nöteberg, D.; Brånalt, J.; Kvarnström, I.; Linschoten, M.; Musil, D.; Nyström, J.E.; Zuccarello, G.; Samuelsson, B. New proline mimetics: Synthesis of thrombin inhibitors incorporating cyclopentane- and cyclopentenedicarboxylic acid templates in the P2 position. Binding conformation investigated by X-ray crystallography. J. Med. Chem., 2000, 43(9), 1705-1713.
[http://dx.doi.org/10.1021/jm990557t] [PMID: 10794688]
[82]
Dahlgren, A.; Brånalt, J.; Kvarnström, I.; Nilsson, I.; Musil, D.; Samuelsson, B. Synthesis of potential thrombin inhibitors. Incorporation of tartaric acid templates as P2 proline mimetics. Bioorg. Med. Chem., 2002, 10(5), 1567-1580.
[http://dx.doi.org/10.1016/S0968-0896(01)00426-6] [PMID: 11886818]
[83]
Thorstensson, F.; Kvarnström, I.; Musil, D.; Nilsson, I.; Samuelsson, B. Synthesis of novel thrombin inhibitors. Use of ring-closing metathesis reactions for synthesis of P2 cyclopentene- and cyclohexenedicarboxylic acid derivatives. J. Med. Chem., 2003, 46(7), 1165-1179.
[http://dx.doi.org/10.1021/jm021065a] [PMID: 12646027]
[84]
Lee, K.; Jung, W.H.; Kang, M.; Lee, S.H. Noncovalent thrombin inhibitors incorporating an imidazolylethynyl P1. Bioorg. Med. Chem. Lett., 2000, 10(24), 2775-2778.
[http://dx.doi.org/10.1016/S0960-894X(00)00579-5] [PMID: 11133089]
[85]
Lee, K.; Jung, W.H.; Park, C.W.; Park, H.D.; Lee, S.H.; Kwon, O.H. Noncovalent tripeptidic thrombin inhibitors incorporating amidrazone, amine and amidine functions at P1. Bioorg. Med. Chem. Lett., 2002, 12(7), 1017-1022.
[http://dx.doi.org/10.1016/S0960-894X(02)00093-8] [PMID: 11909707]
[86]
Lee, K.; Park, C.W.; Jung, W.H.; Park, H.D.; Lee, S.H.; Chung, K.H.; Park, S.K.; Kwon, O.H.; Kang, M.; Park, D.H.; Lee, S.K.; Kim, E.E.; Yoon, S.K.; Kim, A. Efficacious and orally bioavailable thrombin inhibitors based on a 2,5-thienylamidine at the P1 position: Discovery of N-carboxymethyl-d-diphenylalanyl-l-prolyl[(5-amidino-2-thienyl)methyl]amide. J. Med. Chem., 2003, 46(17), 3612-3622.
[http://dx.doi.org/10.1021/jm030025j] [PMID: 12904065]
[87]
Lévesque, S.; St-Denis, Y.; Bachand, B.; Préville, P.; Leblond, L.; Winocour, P.D.; Edmunds, J.J.; Rubin, J.R.; Siddiqui, M.A. Novel bicyclic lactam inhibitors of thrombin: Potency and selectivity optimization through P1 residues. Bioorg. Med. Chem. Lett., 2001, 11(24), 3161-3164.
[http://dx.doi.org/10.1016/S0960-894X(01)00661-8] [PMID: 11720865]
[88]
Danilewicz, J.C.; Abel, S.M.; Brown, A.D.; Fish, P.V.; Hawkeswood, E.; Holland, S.J.; James, K.; McElroy, A.B.; Overington, J.; Powling, M.J.; Rance, D.J. Design of selective thrombin inhibitors based on the (R)-Phe-Pro-Arg sequence. J. Med. Chem., 2002, 45(12), 2432-2453.
[http://dx.doi.org/10.1021/jm011133d] [PMID: 12036353]
[89]
Ho, J.Z.; Gibson, T.S.; Semple, J.E. Novel, potent noncovalent thrombin inhibitors incorporating p(3)-lactam scaffolds. Bioorg. Med. Chem. Lett., 2002, 12(5), 743-748.
[http://dx.doi.org/10.1016/S0960-894X(02)00010-0] [PMID: 11858993]
[90]
Das, J.; Kimball, S.D.; Reid, J.A.; Wang, T.C.; Lau, W.F.; Roberts, D.G.M.; Seiler, S.M.; Schumacher, W.A.; Ogletree, M.L. Thrombin active site inhibitors: Chemical synthesis, in vitro and in vivo pharmacological profile of a novel and selective agent BMS-189090 and analogues. Bioorg. Med. Chem. Lett., 2002, 12(1), 41-44.
[http://dx.doi.org/10.1016/S0960-894X(01)00664-3] [PMID: 11738569]
[91]
Peterlin-Masic, L.; Mlinsek, G.; Solmajer, T.; Trampus-Bakija, A.; Stegnar, M.; Kikelj, D. Novel thrombin inhibitors incorporating non-basic partially saturated heterobicyclic P1-arginine mimetics. Bioorg. Med. Chem. Lett., 2003, 13(5), 789-794.
[http://dx.doi.org/10.1016/S0960-894X(03)00030-1] [PMID: 12617892]
[92]
Marinko, P.; Krbavcic, A.; Mlinsek, G.; Solmajer, T.; Bakija, A.T.; Stegnar, M.; Stojan, J.; Kikelj, D. Novel non-covalent thrombin inhibitors incorporating P(1) 4,5,6,7-tetrahydrobenzothiazole arginine side chain mimetics. Eur. J. Med. Chem., 2004, 39(3), 257-265.
[http://dx.doi.org/10.1016/j.ejmech.2003.12.006] [PMID: 15051174]
[93]
Blizzard, T.A.; Singh, S.; Patil, B.; Chidurala, N.; Komanduri, V.; Debnath, S.; Belyakov, S.; Crespo, A.; Struck, A.; Kurtz, M.; Wiltsie, J.; Shen, X.; Sonatore, L.; Arocho, M.; Lewis, D.; Ogletree, M.; Biftu, T. Heterocyclic core analogs of a direct thrombin inhibitor. Bioorg. Med. Chem. Lett., 2014, 24(4), 1111-1115.
[http://dx.doi.org/10.1016/j.bmcl.2014.01.002] [PMID: 24461292]
[94]
Morrissette, M.M.; Stauffer, K.J.; Williams, P.D.; Lyle, T.A.; Vacca, J.P.; Krueger, J.A.; Lewis, S.D.; Lucas, B.J.; Wong, B.K.; White, R.B.; Miller-Stein, C.; Lyle, E.A.; Wallace, A.A.; Leonard, Y.M.; Welsh, D.C.; Lynch, J.J.; McMasters, D.R. Low molecular weight thrombin inhibitors with excellent potency, metabolic stability, and oral bioavailability. Bioorg. Med. Chem. Lett., 2004, 14(16), 4161-4164.
[http://dx.doi.org/10.1016/j.bmcl.2004.06.030] [PMID: 15261262]
[95]
Stauffer, K.J.; Williams, P.D.; Selnick, H.G.; Nantermet, P.G.; Newton, C.L.; Homnick, C.F.; Zrada, M.M.; Lewis, S.D.; Lucas, B.J.; Krueger, J.A.; Pietrak, B.L.; Lyle, E.A.; Singh, R.; Miller-Stein, C.; White, R.B.; Wong, B.; Wallace, A.A.; Sitko, G.R.; Cook, J.J.; Holahan, M.A.; Stranieri-Michener, M.; Leonard, Y.M.; Lynch, J.J., Jr.; McMasters, D.R.; Yan, Y. 9-hydroxyazafluorenes and their use in thrombin inhibitors. J. Med. Chem., 2005, 48(7), 2282-2293.
[http://dx.doi.org/10.1021/jm049423s] [PMID: 15801822]
[96]
Costanzo, M.J.; Almond, H.R., Jr; Hecker, L.R.; Schott, M.R.; Yabut, S.C.; Zhang, H.C.; Andrade-Gordon, P.; Corcoran, T.W.; Giardino, E.C.; Kauffman, J.A.; Lewis, J.M.; de Garavilla, L.; Haertlein, B.J.; Maryanoff, B.E. In-depth study of tripeptide-based α-ketoheterocycles as inhibitors of thrombin. Effective utilization of the S1′ subsite and its implications to structure-based drug design. J. Med. Chem., 2005, 48(6), 1984-2008.
[http://dx.doi.org/10.1021/jm0303857] [PMID: 15771442]
[97]
Staas, D.D.; Savage, K.L.; Sherman, V.L.; Shimp, H.L.; Lyle, T.A.; Tran, L.O.; Wiscount, C.M.; McMasters, D.R.; Sanderson, P.E.; Williams, P.D.; Lucas, B.J., Jr.; Krueger, J.A.; Lewis, S.D.; White, R.B.; Yu, S.; Wong, B.K.; Kochansky, C.J.; Anari, M.R.; Yan, Y.; Vacca, J.P. Discovery of potent, selective 4-fluoroproline-based thrombin inhibitors with improved metabolic stability. Bioorg. Med. Chem., 2006, 14(20), 6900-6916.
[http://dx.doi.org/10.1016/j.bmc.2006.06.040] [PMID: 16870455]
[98]
Mack, H.; Baucke, D.; Hornberger, W.; Lange, U.E.W.; Seitz, W.; Höffken, H.W. Orally active thrombin inhibitors. Part 1: Optimization of the P1-moiety. Bioorg. Med. Chem. Lett., 2006, 16(10), 2641-2647.
[http://dx.doi.org/10.1016/j.bmcl.2006.02.040] [PMID: 16517159]
[99]
Lange, U.E.; Baucke, D.; Hornberger, W.; Mack, H.; Seitz, W.; Höffken, H.W. Orally active thrombin inhibitors. Part 2: Optimization of the P2-moiety. Bioorg. Med. Chem. Lett., 2006, 16(10), 2648-2653.
[http://dx.doi.org/10.1016/j.bmcl.2006.01.046] [PMID: 16460939]
[100]
Wang, G.; Goyal, N.; Hopkinson, B. Preparation of L-proline based aeruginosin 298-A analogs: Optimization of the P1-moiety. Bioorg. Med. Chem. Lett., 2009, 19(14), 3798-3803.
[http://dx.doi.org/10.1016/j.bmcl.2009.04.056] [PMID: 19447619]
[101]
Figueiredo, A.C.; Clement, C.C.; Zakia, S.; Gingold, J.; Philipp, M.; Pereira, P.J.B. Rational design and characterization of D-Phe-Pro-D-Arg-derived direct thrombin inhibitors. PLoS One, 2012, 7(3), e34354.
[http://dx.doi.org/10.1371/journal.pone.0034354] [PMID: 22457833]
[102]
Chobanian, H.R.; Pio, B.; Guo, Y.; Shen, H.; Huffman, M.A.; Madeira, M.; Salituro, G.; Terebetski, J.L.; Ormes, J.; Jochnowitz, N.; Hoos, L.; Zhou, Y.; Lewis, D.; Hawes, B.; Mitnaul, L.; O’Neill, K.; Ellsworth, K.; Wang, L.; Biftu, T.; Duffy, J.L. Improved stability of proline-derived direct thrombin inhibitors through hydroxyl to heterocycle replacement. ACS Med. Chem. Lett., 2015, 6(5), 553-557.
[http://dx.doi.org/10.1021/acsmedchemlett.5b00047] [PMID: 26005532]
[103]
Abrahamsson, K.; Andersson, P.; Bergman, J.; Bredberg, U.; Branalt, J.; Egnell, A.C.; Eriksson, U.; Gustafsson, D.; Hoffman, K.J.; Nielsen, S.; Nilsson, I.; Pehrsson, S.; Polla, M.O.; Skjaeret, T.; Strimfors, M.; Wern, C.; Olwegard-Halvarsson, M.; Ortengren, Y. Discovery of AZD8165–a clinical candidate from a novel series of neutral thrombin inhibitors. MedChemComm, 2016, 7, 272-281.
[http://dx.doi.org/10.1039/C5MD00479A]
[104]
Hayler, J.; Kane, P.D.; LeGrand, D.; Lugrin, F.; Menear, K.; Price, R.; Allen, M.; Cockcroft, X.; Ambler, J.; Butler, K.; Dunnet, K.; Mitchelson, A.; Talbot, M.; Tweed, M.; Wills, N. The design and synthesis of thrombin inhibitors: The introduction of in vivo efficacy and oral bioavailability into benzthiazolylalanine inhibitors. Bioorg. Med. Chem. Lett., 2000, 10(14), 1567-1570.
[http://dx.doi.org/10.1016/S0960-894X(00)00283-3] [PMID: 10915052]
[105]
Zega, A.; Mlinsek, G.; Sepic, P.; Golic Grdadolnik, S.; Solmajer, T.; Tschopp, T.B.; Steiner, B.; Kikelj, D.; Urleb, U. Design and structure-activity relationship of thrombin inhibitors with an azaphenylalanine scaffold: Potency and selectivity enhancements via P2 optimization. Bioorg. Med. Chem., 2001, 9(10), 2745-2756.
[http://dx.doi.org/10.1016/S0968-0896(01)00202-4] [PMID: 11557360]
[106]
Obreza, A.; Stegnar, M.; Urleb, U. Novel non-covalent azaphenylalanine thrombin inhibitors with an aminomethyl or amino group at the P1 position. Pharmazie, 2004, 59(9), 659-667.
[PMID: 15497744]
[107]
Zega, A.; Mlinsek, G.; Solmajer, T.; Trampus-Bakija, A.; Stegnar, M.; Urleb, U. Thrombin inhibitors built on an azaphenylalanine scaffold. Bioorg. Med. Chem. Lett., 2004, 14(6), 1563-1567.
[http://dx.doi.org/10.1016/j.bmcl.2003.12.083] [PMID: 15006404]
[108]
Obreza, A.; Stegnar, M.; Trampus-Bakija, A.; Prezelj, A.; Urleb, U. Synthesis and in vitro evaluation of new azaphenylalanine derivatives as serine protease inhibitors. Pharmazie, 2004, 59(10), 739-743.
[PMID: 15544050]
[109]
Meneyrol, J.; Follmann, M.; Lassalle, G.; Wehner, V.; Barre, G.; Rousseaux, T.; Altenburger, J.M.; Petit, F.; Bocskei, Z.; Schreuder, H.; Alet, N.; Herault, J.P.; Millet, L.; Dol, F.; Florian, P.; Schaeffer, P.; Sadoun, F.; Klieber, S.; Briot, C.; Bono, F.; Herbert, J.M. 5-Chlorothiophene-2-carboxylic acid [(S)-2-[2-methyl-3-(2-oxopyrrolidin-1-yl)benzenesulfonylamino]-3-(4-methylpiperazin-1-yl)-3-oxopropyl]amide (SAR107375), a selective and potent orally active dual thrombin and factor Xa inhibitor. J. Med. Chem., 2013, 56(23), 9441-9456.
[http://dx.doi.org/10.1021/jm4005835] [PMID: 24175584]
[110]
Coburn, C.A.; Rush, D.M.; Williams, P.D.; Homnick, C.; Lyle, E.A.; Lewis, S.D.; Lucas, B.J., Jr.; Di Muzio-Mower, J.M.; Juliano, M.; Krueger, J.A.; Vastag, K.; Chen, I.W.; Vacca, J.P. Bicyclic pyridones as potent, efficacious and orally bioavailable thrombin inhibitors. Bioorg. Med. Chem. Lett., 2000, 10(10), 1069-1072.
[http://dx.doi.org/10.1016/S0960-894X(00)00170-0] [PMID: 10843219]
[111]
Sanderson, P.E.J.; Cutrona, K.J.; Dyer, D.L.; Krueger, J.A.; Kuo, L.C.; Lewis, S.D.; Lucas, B.J.; Yan, Y. Small, low nanomolar, non-covalent thrombin inhibitors lacking a group to fill the ‘distal binding pocket’. Bioorg. Med. Chem. Lett., 2003, 13(2), 161-164.
[http://dx.doi.org/10.1016/S0960-894X(02)00946-0] [PMID: 12482415]
[112]
Rittle, K.E.; Barrow, J.C.; Cutrona, K.J.; Glass, K.L.; Krueger, J.A.; Kuo, L.C.; Lewis, S.D.; Lucas, B.J.; McMasters, D.R.; Morrissette, M.M.; Nantermet, P.G.; Newton, C.L.; Sanders, W.M.; Yan, Y.; Vacca, J.P.; Selnick, H.G. Unexpected enhancement of thrombin inhibitor potency with o-aminoalkylbenzylamides in the P1 position. Bioorg. Med. Chem. Lett., 2003, 13(20), 3477-3482.
[http://dx.doi.org/10.1016/S0960-894X(03)00732-7] [PMID: 14505652]
[113]
Sanderson, P.E.J.; Stanton, M.G.; Dorsey, B.D.; Lyle, T.A.; McDonough, C.; Sanders, W.M.; Savage, K.L.; Naylor-Olsen, A.M.; Krueger, J.A.; Lewis, S.D.; Lucas, B.J.; Lynch, J.J.; Yan, Y. Azaindoles: Moderately basic P1 groups for enhancing the selectivity of thrombin inhibitors. Bioorg. Med. Chem. Lett., 2003, 13(5), 795-798.
[http://dx.doi.org/10.1016/S0960-894X(03)00017-9] [PMID: 12617893]
[114]
Burgey, C.S.; Robinson, K.A.; Lyle, T.A.; Sanderson, P.E.J.; Lewis, S.D.; Lucas, B.J.; Krueger, J.A.; Singh, R.; Miller-Stein, C.; White, R.B.; Wong, B.; Lyle, E.A.; Williams, P.D.; Coburn, C.A.; Dorsey, B.D.; Barrow, J.C.; Stranieri, M.T.; Holahan, M.A.; Sitko, G.R.; Cook, J.J.; McMasters, D.R.; McDonough, C.M.; Sanders, W.M.; Wallace, A.A.; Clayton, F.C.; Bohn, D.; Leonard, Y.M.; Detwiler, T.J., Jr; Lynch, J.J., Jr; Yan, Y.; Chen, Z.; Kuo, L.; Gardell, S.J.; Shafer, J.A.; Vacca, J.P. Metabolism-directed optimization of 3-aminopyrazinone acetamide thrombin inhibitors. Development of an orally bioavailable series containing P1 and P3 pyridines. J. Med. Chem., 2003, 46(4), 461-473.
[http://dx.doi.org/10.1021/jm020311f] [PMID: 12570369]
[115]
Burgey, C.S.; Robinson, K.A.; Lyle, T.A.; Nantermet, P.G.; Selnick, H.G.; Isaacs, R.C.A.; Lewis, S.D.; Lucas, B.J.; Krueger, J.A.; Singh, R.; Miller-Stein, C.; White, R.B.; Wong, B.; Lyle, E.A.; Stranieri, M.T.; Cook, J.J.; McMasters, D.R.; Pellicore, J.M.; Pal, S.; Wallace, A.A.; Clayton, F.C.; Bohn, D.; Welsh, D.C.; Lynch, J.J., Jr; Yan, Y.; Chen, Z.; Kuo, L.; Gardell, S.J.; Shafer, J.A.; Vacca, J.P. Pharmacokinetic optimization of 3-amino-6-chloropyrazinone acetamide thrombin inhibitors. Implementation of P3 pyridine N-oxides to deliver an orally bioavailable series containing P1 N-benzylamides. Bioorg. Med. Chem. Lett., 2003, 13(7), 1353-1357.
[http://dx.doi.org/10.1016/S0960-894X(03)00099-4] [PMID: 12657281]
[116]
Young, M.B.; Barrow, J.C.; Glass, K.L.; Lundell, G.F.; Newton, C.L.; Pellicore, J.M.; Rittle, K.E.; Selnick, H.G.; Stauffer, K.J.; Vacca, J.P.; Williams, P.D.; Bohn, D.; Clayton, F.C.; Cook, J.J.; Krueger, J.A.; Kuo, L.C.; Lewis, S.D.; Lucas, B.J.; McMasters, D.R.; Miller-Stein, C.; Pietrak, B.L.; Wallace, A.A.; White, R.B.; Wong, B.; Yan, Y.; Nantermet, P.G. Discovery and evaluation of potent P1 aryl heterocycle-based thrombin inhibitors. J. Med. Chem., 2004, 47(12), 2995-3008.
[http://dx.doi.org/10.1021/jm030303e] [PMID: 15163182]
[117]
Peterlin-Masic, L.; Kranjc, A.; Marinko, P.; Mlinsek, G.; Solmajer, T.; Stegnar, M.; Kikelj, D. Selective 3-amino-2-pyridinone acetamide thrombin inhibitors incorporating weakly basic partially saturated heterobicyclic P1-arginine mimetics. Bioorg. Med. Chem. Lett., 2003, 13(19), 3171-3176.
[http://dx.doi.org/10.1016/S0960-894X(03)00717-0] [PMID: 12951087]
[118]
Kranjc, A.; Masic, L.P.; Reven, S.; Mikic, K.; Prezelj, A.; Stegnar, M.; Kikelj, D. Novel pyrazinone and pyridinone thrombin inhibitors incorporating weakly basic heterobicyclic P(1)-arginine mimetics. Eur. J. Med. Chem., 2005, 40(8), 782-791.
[http://dx.doi.org/10.1016/j.ejmech.2005.03.007] [PMID: 15890436]
[119]
Kranjc, A.; Peterlin-Masic, L.; Ilas, J.; Prezelj, A.; Stegnar, M.; Kikelj, D. Novel thrombin inhibitors incorporating weakly basic heterobicyclic P1-arginine mimetics: Optimization via modification of P1 and P3 moieties. Bioorg. Med. Chem. Lett., 2004, 14(12), 3251-3256.
[http://dx.doi.org/10.1016/j.bmcl.2004.03.085] [PMID: 15149685]
[120]
Hanessian, S.; Simard, D.; Bayrakdarian, M.; Therrien, E.; Nilsson, I.; Fjellström, O. Design, synthesis, and thrombin-inhibitory activity of pyridin-2-ones as P2/P3 core motifs. Bioorg. Med. Chem. Lett., 2008, 18(6), 1972-1976.
[http://dx.doi.org/10.1016/j.bmcl.2008.01.122] [PMID: 18289852]
[121]
Hanessian, S.; Therrien, E.; Zhang, J.; Otterlo, Wv.; Xue, Y.; Gustafsson, D.; Nilsson, I.; Fjellström, O. From natural products to achiral drug prototypes: Potent thrombin inhibitors based on P2/P3 dihydropyrid-2-one core motifs. Bioorg. Med. Chem. Lett., 2009, 19(18), 5429-5432.
[http://dx.doi.org/10.1016/j.bmcl.2009.07.107] [PMID: 19674897]
[122]
Isaacs, R.C.A.; Newton, C.L.; Cutrona, K.J.; Mercer, S.P.; Dorsey, B.D.; McDonough, C.M.; Cook, J.J.; Krueger, J.A.; Lewis, S.D.; Lucas, B.J.; Lyle, E.A.; Lynch, J.J.; Miller-Stein, C.; Michener, M.T.; Wallace, A.A.; White, R.B.; Wong, B.K. P3 optimization of functional potency, in vivo efficacy and oral bioavailability in 3-aminopyrazinone thrombin inhibitors bearing non-charged groups at the P1 position. Bioorg. Med. Chem. Lett., 2011, 21(5), 1532-1535.
[http://dx.doi.org/10.1016/j.bmcl.2010.12.108] [PMID: 21295466]
[123]
Lu, T.; Markotan, T.; Ballentine, S.K.; Giardino, E.C.; Spurlino, J.; Crysler, C.S.; Brown, K.; Maryanoff, B.E.; Tomczuk, B.E.; Damiano, B.P.; Shukla, U.; End, D.; Andrade-Gordon, P.; Bone, R.F.; Player, M.R. Discovery and clinical evaluation of 1-N-[2-(amidinoaminooxy)ethyl]aminocarbonylmethyl-6-methyl-3-[2,2-difluoro-2-phenylethylamino]pyrazinone (RWJ-671818), a thrombin inhibitor with an oxyguanidine P1 motif. J. Med. Chem., 2010, 53(4), 1843-1856.
[http://dx.doi.org/10.1021/jm901802n] [PMID: 20102150]
[124]
Lu, T.; Soll, R.M.; Illig, C.R.; Bone, R.; Murphy, L.; Spurlino, J.; Salemme, F.R.; Tomczuk, B.E. Structure-activity and crystallographic analysis of a new class of non-amide-based thrombin inhibitor. Bioorg. Med. Chem. Lett., 2000, 10(1), 79-82.
[http://dx.doi.org/10.1016/S0960-894X(99)00617-4] [PMID: 10636249]
[125]
Tomczuk, B.; Lu, T.; Soll, R.M.; Fedde, C.; Wang, A.; Murphy, L.; Crysler, C.; Dasgupta, M.; Eisennagel, S.; Spurlino, J.; Bone, R. Oxyguanidines: Application to non-peptidic phenyl-based thrombin inhibitors. Bioorg. Med. Chem. Lett., 2003, 13(8), 1495-1498.
[http://dx.doi.org/10.1016/S0960-894X(03)00125-2] [PMID: 12668020]
[126]
Lu, T.; Markotan, T.; Coppo, F.; Tomczuk, B.; Crysler, C.; Eisennagel, S.; Spurlino, J.; Gremminger, L.; Soll, R.M.; Giardino, E.C.; Bone, R. Oxyguanidines. Part 2: Discovery of a novel orally active thrombin inhibitor through structure-based drug design and parallel synthesis. Bioorg. Med. Chem. Lett., 2004, 14(14), 3727-3731.
[http://dx.doi.org/10.1016/j.bmcl.2004.05.002] [PMID: 15203151]
[127]
Lee, L.; Kreutter, K.D.; Pan, W.; Crysler, C.; Spurlino, J.; Player, M.R.; Tomczuk, B.; Lu, T. 2-(2-Chloro-6-fluorophenyl)acetamides as potent thrombin inhibitors. Bioorg. Med. Chem. Lett., 2007, 17(22), 6266-6269.
[http://dx.doi.org/10.1016/j.bmcl.2007.09.013] [PMID: 17889527]
[128]
Kreutter, K.D.; Lu, T.; Lee, L.; Giardino, E.C.; Patel, S.; Huang, H.; Xu, G.; Fitzgerald, M.; Haertlein, B.J.; Mohan, V.; Crysler, C.; Eisennagel, S.; Dasgupta, M.; McMillan, M.; Spurlino, J.C.; Huebert, N.D.; Maryanoff, B.E.; Tomczuk, B.E.; Damiano, B.P.; Player, M.R. Orally efficacious thrombin inhibitors with cyanofluorophenylacetamide as the P2 motif. Bioorg. Med. Chem. Lett., 2008, 18(9), 2865-2870.
[http://dx.doi.org/10.1016/j.bmcl.2008.03.087] [PMID: 18420408]
[129]
Hanessian, S.; Therrien, E.; van Otterlo, W.A.L.; Bayrakdarian, M.; Nilsson, I.; Fjellström, O.; Xue, Y. Phenolic P2/P3 core motif as thrombin inhibitors--design, synthesis, and X-ray co-crystal structure. Bioorg. Med. Chem. Lett., 2006, 16(4), 1032-1036.
[http://dx.doi.org/10.1016/j.bmcl.2005.10.082] [PMID: 16290930]
[130]
Siles, R.; Kawasaki, Y.; Ross, P.; Freire, E. Synthesis and biochemical evaluation of triazole/tetrazole-containing sulfonamides against thrombin and related serine proteases. Bioorg. Med. Chem. Lett., 2011, 21(18), 5305-5309.
[http://dx.doi.org/10.1016/j.bmcl.2011.07.023] [PMID: 21807511]
[131]
de Candia, M.; Fiorella, F.; Lopopolo, G.; Carotti, A.; Romano, M.R.; Lograno, M.D.; Martel, S.; Carrupt, P.A.; Belviso, B.D.; Caliandro, R.; Altomare, C. Synthesis and biological evaluation of direct thrombin inhibitors bearing 4-(piperidin-1-yl)pyridine at the P1 position with potent anticoagulant activity. J. Med. Chem., 2013, 56(21), 8696-8711.
[http://dx.doi.org/10.1021/jm401169a] [PMID: 24102612]
[132]
Blomberg, D.; Fex, T.; Xue, Y.; Brickmann, K.; Kihlberg, J. Design, synthesis and biological evaluation of thrombin inhibitors based on a pyridine scaffold. Org. Biomol. Chem., 2007, 5(16), 2599-2605.
[http://dx.doi.org/10.1039/b705344d] [PMID: 18019535]
[133]
Deng, J.Z.; McMasters, D.R.; Rabbat, P.M.A.; Williams, P.D.; Coburn, C.A.; Yan, Y.; Kuo, L.C.; Lewis, S.D.; Lucas, B.J.; Krueger, J.A.; Strulovici, B.; Vacca, J.P.; Lyle, T.A.; Burgey, C.S. Development of an oxazolopyridine series of dual thrombin/factor Xa inhibitors via structure-guided lead optimization. Bioorg. Med. Chem. Lett., 2005, 15(20), 4411-4416.
[http://dx.doi.org/10.1016/j.bmcl.2005.07.022] [PMID: 16137886]
[134]
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]
[135]
Ries, U.J.; Priepke, H.W.M.; Hauel, N.H.; Haaksma, E.E.J.; Stassen, J.M.; Wienen, W.; Nar, H. Heterocyclic thrombin inhibitors. Part 1: Design and synthesis of amidino-phenoxy quinoline derivatives. Bioorg. Med. Chem. Lett., 2003, 13(14), 2291-2295.
[http://dx.doi.org/10.1016/S0960-894X(03)00442-6] [PMID: 12824020]
[136]
Ries, U.J.; Priepke, H.W.M.; Hauel, N.H.; Handschuh, S.; Mihm, G.; Stassen, J.M.; Wienen, W.; Nar, H. Heterocyclic thrombin inhibitors. Part 2: Quinoxalinone derivatives as novel, potent antithrombotic agents. Bioorg. Med. Chem. Lett., 2003, 13(14), 2297-2302.
[http://dx.doi.org/10.1016/S0960-894X(03)00443-8] [PMID: 12824021]
[137]
Sall, D.J.; Bailey, D.L.; Bastian, J.A.; Buben, J.A.; Chirgadze, N.Y.; Clemens-Smith, A.C.; Denney, M.L.; Fisher, M.J.; Giera, D.D.; Gifford-Moore, D.S.; Harper, R.W.; Johnson, L.M.; Klimkowski, V.J.; Kohn, T.J.; Lin, H.S.; McCowan, J.R.; Palkowitz, A.D.; Richett, M.E.; Smith, G.F.; Snyder, D.W.; Takeuchi, K.; Toth, J.E.; Zhang, M. Diamino benzo[b]thiophene derivatives as a novel class of active site directed thrombin inhibitors. 5. Potency, efficacy, and pharmacokinetic properties of modified C-3 side chain derivatives. J. Med. Chem., 2000, 43(4), 649-663.
[http://dx.doi.org/10.1021/jm9903388] [PMID: 10691691]
[138]
Sidhu, P.S.; Liang, A.; Mehta, A.Y.; Abdel Aziz, M.H.; Zhou, Q.; Desai, U.R. Rational design of potent, small, synthetic allosteric inhibitors of thrombin. J. Med. Chem., 2011, 54(15), 5522-5531.
[http://dx.doi.org/10.1021/jm2005767] [PMID: 21714536]
[139]
Abdel Aziz, M.H.; Sidhu, P.S.; Liang, A.; Kim, J.Y.; Mosier, P.D.; Zhou, Q.; Farrell, D.H.; Desai, U.R. Designing allosteric regulators of thrombin. Monosulfated benzofuran dimers selectively interact with Arg173 of exosite 2 to induce inhibition. J. Med. Chem., 2012, 55(15), 6888-6897.
[http://dx.doi.org/10.1021/jm300670q] [PMID: 22788964]
[140]
Sidhu, P.S.; Abdel Aziz, M.H.; Sarkar, A.; Mehta, A.Y.; Zhou, Q.; Desai, U.R. Designing allosteric regulators of thrombin. Exosite 2 features multiple subsites that can be targeted by sulfated small molecules for inducing inhibition. J. Med. Chem., 2013, 56(12), 5059-5070.
[http://dx.doi.org/10.1021/jm400369q] [PMID: 23718540]
[141]
Sidhu, P.S.; Zhou, Q.; Desai, U.R. A simple, general approach of allosteric coagulation enzyme inhibition through monosulfated hydrophobic scaffolds. Bioorg. Med. Chem. Lett., 2014, 24(24), 5716-5720.
[http://dx.doi.org/10.1016/j.bmcl.2014.10.059] [PMID: 25453807]
[142]
Afosah, D.K.; Verespy, S., III; Al-Horani, R.A.; Boothello, R.S.; Karuturi, R.; Desai, U.R. A small group of sulfated benzofurans induces steady-state submaximal inhibition of thrombin. Bioorg. Med. Chem. Lett., 2018, 28(6), 1101-1105.
[http://dx.doi.org/10.1016/j.bmcl.2018.01.069] [PMID: 29459207]
[143]
Nilsson, J.W.; Kvarnström, I.; Musil, D.; Nilsson, I.; Samulesson, B. Synthesis and SAR of thrombin inhibitors incorporating a novel 4-amino-morpholinone sscaffold: Analysis of X-ray crystal structure of enzyme inhibitor complex. J. Med. Chem., 2003, 46(19), 3985-4001.
[http://dx.doi.org/10.1021/jm0307990] [PMID: 12954052]
[144]
Stefanic Anderluh, P.; Anderluh, M.; Ilas, J.; Mravljak, J.; Sollner Dolenc, M.; Stegnar, M.; Kikelj, D. Toward a novel class of antithrombotic compounds with dual function. Discovery of 1,4-benzoxazin-3(4H)-one derivatives possessing thrombin inhibitory and fibrinogen receptor antagonistic activities. J. Med. Chem., 2005, 48(9), 3110-3113.
[http://dx.doi.org/10.1021/jm048984g] [PMID: 15857114]
[145]
Ilas, J.; Tomasić, T.; Kikelj, D. Novel potent and selective thrombin inhibitors based on a central 1,4-benzoxazin-3(4H)-one scaffold. J. Med. Chem., 2008, 51(9), 2863-2867.
[http://dx.doi.org/10.1021/jm701622y] [PMID: 18412326]
[146]
Ilas, J.; Jakopin, Z.; Borstnar, T.; Stegnar, M.; Kikelj, D. 3,4-Dihydro-2H-1,4-benzoxazine derivatives combining thrombin inhibitory and glycoprotein IIb/IIIa receptor antagonistic activity as a novel class of antithrombotic compounds with dual function. J. Med. Chem., 2008, 51(18), 5617-5629.
[http://dx.doi.org/10.1021/jm8003448] [PMID: 18729445]
[147]
Ilić, M.; Kontogiorgis, C.; Hadjipavlou-Litina, D.; Ilaš, J.; Kikelj, D. Thrombin inhibitors with lipid peroxidation and lipoxygenase inhibitory activities. Bioorg. Med. Chem. Lett., 2011, 21(16), 4705-4709.
[http://dx.doi.org/10.1016/j.bmcl.2011.06.089] [PMID: 21757348]
[148]
Ilić, M.; Kikelj, D.; Ilaš, J. Fluorinated dual antithrombotic compounds based on 1,4-benzoxazine scaffold. Eur. J. Med. Chem., 2012, 50, 255-263.
[http://dx.doi.org/10.1016/j.ejmech.2012.01.059] [PMID: 22365562]
[149]
Baburajeev, C.P.; Mohan, C.D.; Pandey, V.; Rangappa, S.; Shivalingegowda, N.; Kalash, L.; Devaraja, S.; Bender, A.; Lobie, P.E.; Rangappa, K.S.; Basappa Synthesis of CC, CN coupled novel substituted dibutyl benzothiazepinone derivatives and evaluation of their thrombin inhibitory activity. Bioorg. Chem., 2019, 87, 142-154.
[http://dx.doi.org/10.1016/j.bioorg.2019.03.004] [PMID: 30884308]
[150]
Carroll, A.R.; Pierens, G.K.; Fechner, G.; De Almeida Leone, P.; Ngo, A.; Simpson, M.; Hyde, E.; Hooper, J.N.; Boström, S.L.; Musil, D.; Quinn, R.J. Dysinosin A: A novel inhibitor of Factor VIIa and thrombin from a new genus and species of Australian sponge of the family Dysideidae. J. Am. Chem. Soc., 2002, 124(45), 13340-13341.
[http://dx.doi.org/10.1021/ja020814a] [PMID: 12418859]
[151]
Carroll, A.R.; Buchanan, M.S.; Edser, A.; Hyde, E.; Simpson, M.; Quinn, R.J. Dysinosins B-D, inhibitors of factor VIIa and thrombin from the Australian sponge Lamellodysidea chlorea. J. Nat. Prod., 2004, 67(8), 1291-1294.
[http://dx.doi.org/10.1021/np049968p] [PMID: 15332844]
[152]
Zhu, Y.; Zhang, P.; Yu, H.; Li, J.; Wang, M.W.; Zhao, W. Anti-Helicobacter pylori and thrombin inhibitory components from Chinese dragon’s blood, Dracaena cochinchinensis. J. Nat. Prod., 2007, 70(10), 1570-1577.
[http://dx.doi.org/10.1021/np070260v] [PMID: 17883259]
[153]
Shi, D.; Li, X.; Li, J.; Guo, S.; Su, H.; Fan, X. Antithrombotic effects of bromophenol, an alga-derived thrombin inhibitor. Chin. J. Oceanol. Limnol., 2010, 28, 96-98.
[http://dx.doi.org/10.1007/s00343-010-9213-0]
[154]
Liu, L.; Ma, H.; Yang, N.; Tang, Y.; Guo, J.; Tao, W.; Duan, J. A series of natural flavonoids as thrombin inhibitors: Structure-activity relationships. Thromb. Res., 2010, 126(5), e365-e378.
[http://dx.doi.org/10.1016/j.thromres.2010.08.006] [PMID: 20828797]
[155]
Anas, A.R.J.; Kisugi, T.; Umezawa, T.; Matsuda, F.; Campitelli, M.R.; Quinn, R.J.; Okino, T. Thrombin inhibitors from the freshwater cyanobacterium Anabaena compacta. J. Nat. Prod., 2012, 75(9), 1546-1552.
[http://dx.doi.org/10.1021/np300282a] [PMID: 22950366]
[156]
de Andrade Moura, L.; Marqui de Almeida, A.C.; Domingos, T.F.S.; Ortiz-Ramirez, F.; Cavalcanti, D.N.V.; Teixeira, V.L.; Fuly, A.L. Antiplatelet and anticoagulant effects of diterpenes isolated from the marine alga, Dictyota menstrualis. Mar. Drugs, 2014, 12(5), 2471-2484.
[http://dx.doi.org/10.3390/md12052471] [PMID: 24796305]
[157]
Lu, J.; Song, H.P.; Li, P.; Zhou, P.; Dong, X.; Chen, J. Screening of direct thrombin inhibitors from Radix Salviae Miltiorrhizae by a peak fractionation approach. J. Pharmaceut. Biomed., 2015, 109, 85-90.
[http://dx.doi.org/10.1016/j.jpba.2015.02.020] [PMID: 25819728]
[158]
Rodrigues, C.F.B.; Gaeta, H.H.; Belchor, M.N.; Ferreira, M.J.P.; Pinho, M.V.T.; Toyama, Dde.O.; Toyama, M.H. Evaluation of potential thrombin inhibitors from the white mangrove (Laguncularia racemosa (L.) C.F. Gaertn.). Mar. Drugs, 2015, 13(7), 4505-4519.
[http://dx.doi.org/10.3390/md13074505] [PMID: 26197325]
[159]
Gogoi, D.; Pal, A.; Chattopadhyay, P.; Paul, S.; Deka, R.C.; Mukherjee, A.K. First report of plant-derived β-sitosterol with antithrombotic, in vivoanticoagulant, and thrombus-preventing ativities in a mouse model. J. Nat. Prod., 2018, 81(11), 2521-2530.
[http://dx.doi.org/10.1021/acs.jnatprod.8b00574] [PMID: 30406661]
[160]
Yu, X.; Wei, L.H.; Zhang, J.K.; Chen, T.R.; Jin, Q.; Wang, Y.N.; Zhang, S.J.; Dou, T.Y.; Cao, Y.F.; Guo, W.Z.; Ge, G.B.; Yang, L. Anthraquinones from Cassiae semen as thrombin inhibitors: in vitro and in silico studies. Phytochemistry, 2019, 165, 112025.
[http://dx.doi.org/10.1016/j.phytochem.2019.04.018] [PMID: 31207449]
[161]
Wei, L.H.; Chen, T.R.; Fang, H.B.; Jin, Q.; Zhang, S.J.; Hou, J.; Yu, Y.; Dou, T.Y.; Cao, Y.F.; Guo, W.Z.; Ge, G.B. Natural constituents of St. John’s Wort inhibit the proteolytic activity of human thrombin. Int. J. Biol. Macromol., 2019, 134, 622-630.
[http://dx.doi.org/10.1016/j.ijbiomac.2019.04.181] [PMID: 31047931]
[162]
Chen, T.R.; Wei, L.H.; Guan, X.Q.; Huang, C.; Liu, Z.Y.; Wang, F.J.; Hou, J.; Jin, Q.; Liu, Y.F.; Wen, P.H.; Zhang, S.J.; Ge, G.B.; Guo, W.Z. Biflavones from Ginkgo biloba as inhibitors of human thrombin. Bioorg. Chem., 2019, 92, 103199.
[http://dx.doi.org/10.1016/j.bioorg.2019.103199] [PMID: 31446241]
[163]
Wen, F.; Chen, T.; Yin, H.; Lin, J.; Zhang, H. In vitro effects on thrombin of paris saponins and in vivo hemostatic activity evaluation of Paris fargesii var. Brevipetala. Molecules, 2019, 24, 1420.
[http://dx.doi.org/10.3390/molecules24071420]
[164]
Wang, L.; Ma, Q. Clinical benefits and pharmacology of scutellarin: A comprehensive review. Pharmacol. Ther., 2018, 190, 105-127.
[http://dx.doi.org/10.1016/j.pharmthera.2018.05.006] [PMID: 29742480]
[165]
Qing, G.E.; Zhou, Z.; Zhi, X.; Ma, L.; Chen, X. Pharmacokinetics and absolute bioavailability of breviscapine in beagle dogs. Carol. J. Pharm., 2003, 34, 618-620.
[166]
Xing, J.F.; You, H.S.; Dong, Y.L.; Lu, J.; Chen, S.Y.; Zhu, H.F.; Dong, Q.; Wang, M.Y.; Dong, W.H. Metabolic and pharmacokinetic studies of scutellarin in rat plasma, urine, and feces. Acta Pharmacol. Sin., 2011, 32(5), 655-663.
[http://dx.doi.org/10.1038/aps.2011.11] [PMID: 21516133]
[167]
Li, N.G.; Song, S.L.; Shen, M.Z.; Tang, Y.P.; Shi, Z.H.; Tang, H.; Shi, Q.P.; Fu, Y.F.; Duan, J.A. Mannich bases of scutellarein as thrombin-inhibitors: Design, synthesis, biological activity and solubility. Bioorg. Med. Chem., 2012, 20(24), 6919-6923.
[http://dx.doi.org/10.1016/j.bmc.2012.10.015] [PMID: 23131413]
[168]
Li, N.G.; Shen, M.Z.; Wang, Z.J.; Tang, Y.P.; Shi, Z.H.; Fu, Y.F.; Shi, Q.P.; Tang, H.; Duan, J.A. Design, synthesis and biological evaluation of glucose-containing scutellarein derivatives as neuroprotective agents based on metabolic mechanism of scutellarin in vivo. Bioorg. Med. Chem. Lett., 2013, 23(1), 102-106.
[http://dx.doi.org/10.1016/j.bmcl.2012.11.002] [PMID: 23177255]
[169]
Shi, Z.H.; Li, N.G.; Shi, Q.P.; Zhang, W.; Dong, Z.X.; Tang, Y.P.; Zhang, P.X.; Gu, T.; Wu, W.Y.; Fang, F.; Xin-Xue; Li, H.M.; Yang, J.P.; Duan, J.A. Synthesis of scutellarein derivatives to increase biological activity and water solubility. Bioorg. Med. Chem., 2015, 23(21), 6875-6884.
[http://dx.doi.org/10.1016/j.bmc.2015.09.047] [PMID: 26455656]
[170]
Shi, Z.H.; Li, N.G.; Wang, Z.J.; Tang, Y.P.; Dong, Z.X.; Zhang, W.; Zhang, P.X.; Gu, T.; Wu, W.Y.; Yang, J.P.; Duan, J.A. Synthesis and biological evaluation of methylated scutellarein analogs based on metabolic mechanism of scutellarin in vivo. Eur. J. Med. Chem., 2015, 106, 95-105.
[http://dx.doi.org/10.1016/j.ejmech.2015.10.039] [PMID: 26523667]
[171]
Frédérick, R.; Robert, S.; Charlier, C.; de Ruyck, J.; Wouters, J.; Pirotte, B.; Masereel, B.; Pochet, L. 3,6-disubstituted coumarins as mechanism-based inhibitors of thrombin and factor Xa. J. Med. Chem., 2005, 48(24), 7592-7603.
[http://dx.doi.org/10.1021/jm050448g] [PMID: 16302799]
[172]
Frédérick, R.; Charlier, C.; Robert, S.; Wouters, J.; Masereel, B.; Pochet, L. Investigation of mechanism-based thrombin inhibitors: Implications of a highly conserved water molecule for the binding of coumarins within the S pocket. Bioorg. Med. Chem. Lett., 2006, 16(7), 2017-2021.
[http://dx.doi.org/10.1016/j.bmcl.2005.12.070] [PMID: 16413781]
[173]
Frédérick, R.; Robert, S.; Charlier, C.; Wouters, J.; Masereel, B.; Pochet, L. Mechanism-based thrombin inhibitors: Design, synthesis, and molecular docking of a new selective 2-oxo-2H-1-benzopyran derivative. J. Med. Chem., 2007, 50(15), 3645-3650.
[http://dx.doi.org/10.1021/jm061368v] [PMID: 17580844]
[174]
Verespy, S., III; Mehta, A.Y.; Afosah, D.; Al-Horani, R.A.; Desai, U.R. Allosteric partial inhibition of monomeric proteases. Sulfated coumarins induce regulation, not just inhibition, of thrombin. Sci. Rep., 2016, 6, 24043.
[http://dx.doi.org/10.1038/srep24043] [PMID: 27053426]
[175]
Žula, A.; Będziak, I.; Kikelj, D.; Ilaš, J. Synthesis and evaluation of spumigin analogues library with thrombin inhibitory activity. Mar. Drugs, 2018, 16(11), 413.
[http://dx.doi.org/10.3390/md16110413] [PMID: 30373260]
[176]
Lu, S.; Wang, J.; Sheng, R.; Fang, Y.; Guo, R. Novel bioactive polyketides isolated from marine actinomycetes: An update review from 2013 to 2019. Chem. Biodivers., 2020, 17(12), e2000562.
[http://dx.doi.org/10.1002/cbdv.202000562] [PMID: 33206470]
[177]
Wang, J.; Su, S.; Zhang, S.; Zhai, S.; Sheng, R.; Wu, W.; Guo, R. Structure-activity relationship and synthetic methodologies of α-santonin derivatives with diverse bioactivities: A mini-review. Eur. J. Med. Chem., 2019, 175, 215-233.
[http://dx.doi.org/10.1016/j.ejmech.2019.04.066] [PMID: 31082765]
[178]
Guo, R.; Guo, C.; He, D.; Zhao, D.; Shen, Y. Two new C19-diterpenoid alkaloids with anti-inflammatory activity from Aconitum iochanicum. Chin. J. Chem., 2017, 35, 1644-1647.
[http://dx.doi.org/10.1002/cjoc.201700401]

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