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Cardiovascular & Hematological Agents in Medicinal Chemistry

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ISSN (Print): 1871-5257
ISSN (Online): 1875-6182

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Research Article

Triazol-1-yl Benzamides Promote Anticoagulant Activity via Inhibition of Factor XIIa

Author(s): Rami A. Al-Horani*, Daniel K. Afosah and Madhusoodanan Mottamal

Volume 21, Issue 2, 2023

Published on: 19 December, 2022

Page: [108 - 119] Pages: 12

DOI: 10.2174/1871525721666221031141323

Price: $65

Abstract

Background: Human factor XIIa (FXIIa) is a plasma serine protease that plays a significant role in several physiological and pathological processes. Animal models have revealed an important contribution of FXIIa to thromboembolic diseases. Remarkably, animals and patients with FXII deficiency appear to have normal hemostasis. Thus, FXIIa inhibition may serve as a promising therapeutic strategy to attain safer and more effective anticoagulation. Very few small molecule inhibitors of FXIIa have been reported. We synthesized and investigated a focused library of triazol-1-yl benzamide derivatives for FXIIa inhibition.

Methods: We chemically synthesized, characterized, and investigated a focused library of triazol- 1-yl benzamide derivatives for FXIIa inhibition. Using a standardized chromogenic substrate hydrolysis assay, the derivatives were evaluated for inhibiting human FXIIa. Their selectivity over other clotting factors was also evaluated using the corresponding substrate hydrolysis assays. The best inhibitor affinity to FXIIa was also determined using fluorescence spectroscopy. Effects on the clotting times (prothrombin time (PT) and activated partial thromboplastin time (APTT)) of human plasma were also studied.

Results: We identified a specific derivative (1) as the most potent inhibitor in this series. The inhibitor exhibited nanomolar binding affinity to FXIIa. It also exhibited significant selectivity against several serine proteases. It also selectively doubled the activated partial thromboplastin time of human plasma.

Conclusion: Overall, this work puts forward inhibitor 1 as a potent and selective inhibitor of FXIIa for further development as an anticoagulant.

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Graphical Abstract

[1]
Schmaier, A.H.; Stavrou, E.X. Factor XII - What’s important but not commonly thought about. Res. Pract. Thromb. Haemost., 2019, 3(4), 599-606.
[http://dx.doi.org/10.1002/rth2.12235] [PMID: 31624779]
[2]
Rawlings, N.D.; Barrett, A.J.; Thomas, P.D.; Huang, X.; Bateman, A.; Finn, R.D. The MEROPS database of proteolytic enzymes, their substrates and inhibitors in 2017 and a comparison with peptidases in the PANTHER database. Nucleic Acids Res., 2018, 46(D1), D624-D632.
[http://dx.doi.org/10.1093/nar/gkx1134] [PMID: 29145643]
[3]
Zamolodchikov, D.; Bai, Y.; Tang, Y.; McWhirter, J.R.; Macdonald, L.E.; Alessandri-Haber, N. A short isoform of coagulation factor XII mRNA is expressed by neurons in the human brain. Neuroscience, 2019, 413, 294-307.
[http://dx.doi.org/10.1016/j.neuroscience.2019.05.040] [PMID: 31181367]
[4]
Stavrou, E.X.; Fang, C.; Bane, K.L.; Long, A.T.; Naudin, C.; Kucukal, E.; Gandhi, A.; Brett-Morris, A.; Mumaw, M.M.; Izadmehr, S.; Merkulova, A.; Reynolds, C.C.; Alhalabi, O.; Nayak, L.; Yu, W.M.; Qu, C.K.; Meyerson, H.J.; Dubyak, G.R.; Gurkan, U.A.; Nieman, M.T.; Sen Gupta, A.; Renné, T.; Schmaier, A.H. Factor XII and uPAR upregulate neutrophil functions to influence wound healing. J. Clin. Invest., 2018, 128(3), 944-959.
[http://dx.doi.org/10.1172/JCI92880] [PMID: 29376892]
[5]
Didiasova, M.; Wujak, L.; Schaefer, L.; Wygrecka, M. Factor XII in coagulation, inflammation and beyond. Cell. Signal., 2018, 51, 257-265.
[http://dx.doi.org/10.1016/j.cellsig.2018.08.006] [PMID: 30118759]
[6]
Stavrou, E.; Schmaier, A.H. Factor XII: What does it contribute to our understanding of the physiology and pathophysiology of hemostasis & thrombosis. Thromb. Res., 2010, 125(3), 210-215.
[http://dx.doi.org/10.1016/j.thromres.2009.11.028] [PMID: 20022081]
[7]
de Maat, S.; Maas, C. Factor XII: Form determines function. J. Thromb. Haemost., 2016, 14(8), 1498-1506.
[http://dx.doi.org/10.1111/jth.13383] [PMID: 27282310]
[8]
Weidmann, H.; Heikaus, L.; Long, A.T.; Naudin, C.; Schlüter, H.; Renné, T. The plasma contact system, a protease cascade at the nexus of inflammation, coagulation and immunity. Biochim. Biophys. Acta Mol. Cell Res., 2017, 1864(11), 2118-2127.
[http://dx.doi.org/10.1016/j.bbamcr.2017.07.009] [PMID: 28743596]
[9]
Salvesen, G.S.; Catanese, J.J.; Kress, L.F.; Travis, J. Primary structure of the reactive site of human C1-inhibitor. J. Biol. Chem., 1985, 260(4), 2432-2436.
[http://dx.doi.org/10.1016/S0021-9258(18)89572-2] [PMID: 3919001]
[10]
Davoine, C.; Bouckaert, C.; Fillet, M.; Pochet, L. Factor XII/XIIa inhibitors: Their discovery, development, and potential indications. Eur. J. Med. Chem., 2020, 208, 112753.
[http://dx.doi.org/10.1016/j.ejmech.2020.112753] [PMID: 32883641]
[11]
Farkas, H. Hereditary angioedema: Examining the landscape of therapies and preclinical therapeutic targets. Expert Opin. Ther. Targets, 2019, 23(6), 457-459.
[http://dx.doi.org/10.1080/14728222.2019.1608949] [PMID: 31018718]
[12]
Philippou, H. Heavy chain of FXII: Not an innocent bystander. Blood, 2019, 133(10), 1008-1009.
[http://dx.doi.org/10.1182/blood-2019-01-895110] [PMID: 30846509]
[13]
Björkqvist, J.; de Maat, S.; Lewandrowski, U.; Di Gennaro, A.; Oschatz, C.; Schönig, K.; Nöthen, M.M.; Drouet, C.; Braley, H.; Nolte, M.W.; Sickmann, A.; Panousis, C.; Maas, C.; Renné, T. Defective glycosylation of coagulation factor XII underlies hereditary angioedema type III. J. Clin. Invest., 2015, 125(8), 3132-3146.
[http://dx.doi.org/10.1172/JCI77139] [PMID: 26193639]
[14]
Tillman, B.; Gailani, D. Inhibition of factors XI and XII for prevention of thrombosis induced by artificial surfaces. Semin. Thromb. Hemost., 2018, 44(1), 060-069.
[http://dx.doi.org/10.1055/s-0037-1603937] [PMID: 28898903]
[15]
Weitz, J.I.; Fredenburgh, J.C. Factors XI and XII as targets for new anticoagulants. Front. Med., 2017, 4, 19.
[http://dx.doi.org/10.3389/fmed.2017.00019] [PMID: 28286749]
[16]
Raghunathan, V.; Zilberman-Rudenko, J.; Olson, S.R.; Lupu, F.; McCarty, O.J.T.; Shatzel, J.J. The contact pathway and sepsis. Res. Pract. Thromb. Haemost., 2019, 3(3), 331-339.
[http://dx.doi.org/10.1002/rth2.12217] [PMID: 31294319]
[17]
Göbel, K.; Pankratz, S.; Asaridou, C.M.; Herrmann, A.M.; Bittner, S.; Merker, M.; Ruck, T.; Glumm, S.; Langhauser, F.; Kraft, P.; Krug, T.F.; Breuer, J.; Herold, M.; Gross, C.C.; Beckmann, D.; Korb-Pap, A.; Schuhmann, M.K.; Kuerten, S.; Mitroulis, I.; Ruppert, C.; Nolte, M.W.; Panousis, C.; Klotz, L.; Kehrel, B.; Korn, T.; Langer, H.F.; Pap, T.; Nieswandt, B.; Wiendl, H.; Chavakis, T.; Kleinschnitz, C.; Meuth, S.G. Blood coagulation factor XII drives adaptive immunity during neuroinflammation via CD87-mediated modulation of dendritic cells. Nat. Commun., 2016, 7(1), 11626.
[http://dx.doi.org/10.1038/ncomms11626] [PMID: 27188843]
[18]
Ziliotto, N.; Baroni, M.; Straudi, S.; Manfredini, F.; Mari, R.; Menegatti, E.; Voltan, R.; Secchiero, P.; Zamboni, P.; Basaglia, N.; Marchetti, G.; Bernardi, F. Coagulation factor XII levels and intrinsic thrombin generation in multiple sclerosis. Front. Neurol., 2018, 9, 245.
[http://dx.doi.org/10.3389/fneur.2018.00245] [PMID: 29731736]
[19]
Zamolodchikov, D.; Chen, Z.L.; Conti, B.A.; Renné, T.; Strickland, S. Activation of the factor XII-driven contact system in Alzheimer’s disease patient and mouse model plasma. Proc. Natl. Acad. Sci. USA, 2015, 112(13), 4068-4073.
[http://dx.doi.org/10.1073/pnas.1423764112] [PMID: 25775543]
[20]
Zamolodchikov, D.; Renné, T.; Strickland, S. The Alzheimer’s disease peptide β-amyloid promotes thrombin generation through activation of coagulation factor XII. J. Thromb. Haemost., 2016, 14(5), 995-1007.
[http://dx.doi.org/10.1111/jth.13209] [PMID: 26613657]
[21]
Chen, Z.L.; Revenko, A.S.; Singh, P.; MacLeod, A.R.; Norris, E.H.; Strickland, S. Depletion of coagulation factor XII ameliorates brain pathology and cognitive impairment in Alzheimer disease mice. Blood, 2017, 129(18), 2547-2556.
[http://dx.doi.org/10.1182/blood-2016-11-753202] [PMID: 28242605]
[22]
Hopp, S.; Albert-Weissenberger, C.; Mencl, S.; Bieber, M.; Schuhmann, M.K.; Stetter, C.; Nieswandt, B.; Schmidt, P.M.; Monoranu, C.M.; Alafuzoff, I.; Marklund, N.; Nolte, M.W.; Sirén, A.L.; Kleinschnitz, C. Targeting coagulation factor XII as a novel therapeutic option in brain trauma. Ann. Neurol., 2016, 79(6), 970-982.
[http://dx.doi.org/10.1002/ana.24655] [PMID: 27043916]
[23]
Hopp, S.; Nolte, M.W.; Stetter, C.; Kleinschnitz, C.; Sirén, A.L.; Albert-Weissenberger, C. Alle via tion of secondary brain injury, posttraumatic inflammation, and brain edema formation by inhibition of factor XIIa. J. Neuroinflammation, 2017, 14(1), 39.
[http://dx.doi.org/10.1186/s12974-017-0815-8] [PMID: 28219400]
[24]
Albert-Weissenberger, C.; Hopp, S.; Nieswandt, B.; Sirén, A.L.; Kleinschnitz, C.; Stetter, C. How is the formation of microthrombi after traumatic brain injury linked to inflammation? J. Neuroimmunol., 2019, 326, 9-13.
[http://dx.doi.org/10.1016/j.jneuroim.2018.10.011] [PMID: 30445364]
[25]
Girolami, A.; Candeo, N.; De Marinis, G.B.; Bonamigo, E.; Girolami, B. Comparative incidence of thrombosis in reported cases of deficiencies of factors of the contact phase of blood coagulation. J. Thromb. Thrombolysis, 2011, 31(1), 57-63.
[http://dx.doi.org/10.1007/s11239-010-0495-z] [PMID: 20577781]
[26]
Gailani, D.; Renné, T. The intrinsic pathway of coagulation: A target for treating thromboembolic disease? J. Thromb. Haemost., 2007, 5(6), 1106-1112.
[http://dx.doi.org/10.1111/j.1538-7836.2007.02446.x] [PMID: 17388803]
[27]
Renné, T.; Pozgajová, M.; Grüner, S.; Schuh, K.; Pauer, H.U.; Burfeind, P.; Gailani, D.; Nieswandt, B. Defective thrombus formation in mice lacking coagulation factor XII. J. Exp. Med., 2005, 202(2), 271-281.
[http://dx.doi.org/10.1084/jem.20050664] [PMID: 16009717]
[28]
Kleinschnitz, C.; Stoll, G.; Bendszus, M.; Schuh, K.; Pauer, H.U.; Burfeind, P.; Renné, C.; Gailani, D.; Nieswandt, B.; Renné, T. Targeting coagulation factor XII provides protection from pathological thrombosis in cerebral ischemia without interfering with hemostasis. J. Exp. Med., 2006, 203(3), 513-518.
[http://dx.doi.org/10.1084/jem.20052458] [PMID: 16533887]
[29]
Müller, F.; Mutch, N.J.; Schenk, W.A.; Smith, S.A.; Esterl, L.; Spronk, H.M.; Schmidbauer, S.; Gahl, W.A.; Morrissey, J.H.; Renné, T. Platelet polyphosphates are proinflammatory and procoagulant mediators in vivo. Cell, 2009, 139(6), 1143-1156.
[http://dx.doi.org/10.1016/j.cell.2009.11.001] [PMID: 20005807]
[30]
Larsson, M.; Rayzman, V.; Nolte, M.W.; Nickel, K.F.; Björkqvist, J.; Jämsä, A.; Hardy, M.P.; Fries, M.; Schmidbauer, S.; Hedenqvist, P.; Broomé, M.; Pragst, I.; Dickneite, G.; Wilson, M.J.; Nash, A.D.; Panousis, C.; Renné, T. A factor XIIa inhibitory antibody provides thromboprotection in extracorporeal circulation without increasing bleeding risk. Sci. Transl. Med., 2014, 6(222), 222ra17.
[http://dx.doi.org/10.1126/scitranslmed.3006804] [PMID: 24500405]
[31]
Hagedorn, I.; Schmidbauer, S.; Pleines, I.; Kleinschnitz, C.; Kronthaler, U.; Stoll, G.; Dickneite, G.; Nieswandt, B. Factor XIIa inhibitor recombinant human albumin Infestin-4 abolishes occlusive arterial thrombus formation without affecting bleeding. Circulation, 2010, 121(13), 1510-1517.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.109.924761] [PMID: 20308613]
[32]
Xu, Y.; Cai, T.Q.; Castriota, G.; Zhou, Y.; Hoos, L.; Jochnowitz, N.; Loewrigkeit, C.; Cook, J.; Wickham, A.; Metzger, J.; Ogletree, M.; Seiffert, D.; Chen, Z. Factor XIIa inhibition by Infestin-4: In vitro mode of action and in vivo antithrombotic benefit. Thromb. Haemost., 2014, 111(4), 694-704.
[http://dx.doi.org/10.1160/TH13-08-0668] [PMID: 24336918]
[33]
Chen, J.W.; Figueiredo, J.L.; Wojtkiewicz, G.R.; Siegel, C.; Iwamoto, Y.; Kim, D.E.; Nolte, M.W.; Dickneite, G.; Weissleder, R.; Nahrendorf, M. Selective factor XIIa inhibition attenuates silent brain ischemia: Application of molecular imaging targeting coagulation pathway. JACC Cardiovasc. Imaging, 2012, 5(11), 1127-1138.
[http://dx.doi.org/10.1016/j.jcmg.2012.01.025] [PMID: 23153913]
[34]
May, F.; Krupka, J.; Fries, M.; Thielmann, I.; Pragst, I.; Weimer, T.; Panousis, C.; Nieswandt, B.; Stoll, G.; Dickneite, G.; Schulte, S.; Nolte, M.W. FXIIa inhibitor rHA-Infestin-4: Safe thromboprotection in experimental venous, arterial and foreign surface-induced thrombosis. Br. J. Haematol., 2016, 173(5), 769-778.
[http://dx.doi.org/10.1111/bjh.13990] [PMID: 27018425]
[35]
Revenko, A.S.; Gao, D.; Crosby, J.R.; Bhattacharjee, G.; Zhao, C.; May, C.; Gailani, D.; Monia, B.P.; MacLeod, A.R. Selective depletion of plasma prekallikrein or coagulation factor XII inhibits thrombosis in mice without increased risk of bleeding. Blood, 2011, 118(19), 5302-5311.
[http://dx.doi.org/10.1182/blood-2011-05-355248] [PMID: 21821705]
[36]
Yau, J.W.; Liao, P.; Fredenburgh, J.C.; Stafford, A.R.; Revenko, A.S.; Monia, B.P.; Weitz, J.I. Selective depletion of factor XI or factor XII with antisense oligonucleotides attenuates catheter thrombosis in rabbits. Blood, 2014, 123(13), 2102-2107.
[http://dx.doi.org/10.1182/blood-2013-12-540872] [PMID: 24501216]
[37]
Matafonov, A.; Leung, P.Y.; Gailani, A.E.; Grach, S.L.; Puy, C.; Cheng, Q.; Sun, M.; McCarty, O.J.T.; Tucker, E.I.; Kataoka, H.; Renné, T.; Morrissey, J.H.; Gruber, A.; Gailani, D. Factor XII inhibition reduces thrombus formation in a primate thrombosis model. Blood, 2014, 123(11), 1739-1746.
[http://dx.doi.org/10.1182/blood-2013-04-499111] [PMID: 24408325]
[38]
Iwaki, T.; Cruz-Topete, D.; Castellino, F.J. A complete factor XII deficiency does not affect coagulopathy, inflammatory responses, and lethality, but attenuates early hypotension in endotoxemic mice. J. Thromb. Haemost., 2008, 6(11), 1993-1995.
[http://dx.doi.org/10.1111/j.1538-7836.2008.03142.x] [PMID: 18761719]
[39]
Stroo, I.; Zeerleder, S.; Ding, C.; Luken, B.; Roelofs, J.; de Boer, O.; Meijers, J.; Castellino, F.; van ’t Veer, C.; van der Poll, T. Coagulation factor XI improves host defence during murine pneumonia-derived sepsis independent of factor XII activation. Thromb. Haemost., 2017, 117(8), 1601-1614.
[http://dx.doi.org/10.1160/TH16-12-0920] [PMID: 28492700]
[40]
Stroo, I.; Ding, C.; Novak, A.; Yang, J.; Roelofs, J.J.T.H.; Meijers, J.C.M.; Revenko, A.S.; van’t Veer, C.; Zeerleder, S.; Crosby, J.R.; van der Poll, T. Inhibition of the extrinsic or intrinsic coagulation pathway during pneumonia-derived sepsis. Am. J. Physiol. Lung Cell. Mol. Physiol., 2018, 315(5), L799-L809.
[http://dx.doi.org/10.1152/ajplung.00014.2018] [PMID: 30136609]
[41]
Tucker, E.I.; Verbout, N.G.; Leung, P.Y.; Hurst, S.; McCarty, O.J.T.; Gailani, D.; Gruber, A. Inhibition of factor XI activation attenuates inflammation and coagulopathy while improving the survival of mouse polymicrobial sepsis. Blood, 2012, 119(20), 4762-4768.
[http://dx.doi.org/10.1182/blood-2011-10-386185] [PMID: 22442348]
[42]
Pixley, R.A.; De La Cadena, R.; Page, J.D.; Kaufman, N.; Wyshock, E.G.; Chang, A.; Taylor, F.B., Jr; Colman, R.W. The contact system contributes to hypotension but not disseminated intravascular coagulation in lethal bacteremia. In vivo use of a monoclonal anti-factor XII antibody to block contact activation in baboons. J. Clin. Invest., 1993, 91(1), 61-68.
[http://dx.doi.org/10.1172/JCI116201] [PMID: 7678610]
[43]
Jansen, P.M.; Pixley, R.A.; Brouwer, M.; de Jong, I.W.; Chang, A.C.; Hack, C.E.; Taylor, F.B.J., Jr; Colman, R.W. Inhibition of factor XII in septic baboons attenuates the activation of complement and fibrinolytic systems and reduces the release of interleukin-6 and neutrophil elastase. Blood, 1996, 87(6), 2337-2344.
[http://dx.doi.org/10.1182/blood.V87.6.2337.bloodjournal8762337] [PMID: 8630396]
[44]
Silasi, R.; Keshari, R.S.; Lupu, C.; Van Rensburg, W.J.; Chaaban, H.; Regmi, G.; Shamanaev, A.; Shatzel, J.J.; Puy, C.; Lorentz, C.U.; Tucker, E.I.; Gailani, D.; Gruber, A.; McCarty, O.J.T.; Lupu, F. Inhibition of contact-mediated activation of factor XI protects baboons against S aureus-induced organ damage and death. Blood Adv., 2019, 3(4), 658-669.
[http://dx.doi.org/10.1182/bloodadvances.2018029983] [PMID: 30808684]
[45]
Mackman, N.; Bergmeier, W.; Stouffer, G.A.; Weitz, J.I. Therapeutic strategies for thrombosis: New targets and approaches. Nat. Rev. Drug Discov., 2020, 19(5), 333-352.
[http://dx.doi.org/10.1038/s41573-020-0061-0] [PMID: 32132678]
[46]
Kalinin, D.V. Factor XII(a) inhibitors: A review of the patent literature. Expert Opin. Ther. Pat., 2021, 1-22.
[47]
Korff, M.; Imberg, L.; Will, J.M.; Bückreiß, N.; Kalinina, S.A.; Wenzel, B.M.; Kastner, G.A.; Daniliuc, C.G.; Barth, M.; Ovsepyan, R.A.; Butov, K.R.; Humpf, H.U.; Lehr, M.; Panteleev, M.A.; Poso, A.; Karst, U.; Steinmetzer, T.; Bendas, G.; Kalinin, D.V. Acylated 1 H -1,2,4-triazol-5-amines targeting human coagulation factor XIIa and thrombin: Conventional and microscale synthesis, anticoagulant properties, and mechanism of action. J. Med. Chem., 2020, 63(21), 13159-13186.
[http://dx.doi.org/10.1021/acs.jmedchem.0c01635] [PMID: 33089691]
[48]
Bouckaert, C.; Serra, S.; Rondelet, G.; Dolušić, E.; Wouters, J.; Dogné, J.M.; Frédérick, R.; Pochet, L. Synthesis, evaluation and structure-activity relationship of new 3-carboxamide coumarins as FXIIa inhibitors. Eur. J. Med. Chem., 2016, 110, 181-194.
[http://dx.doi.org/10.1016/j.ejmech.2016.01.023] [PMID: 26827162]
[49]
Dementiev, A.; Silva, A.; Yee, C.; Li, Z.; Flavin, M.T.; Sham, H.; Partridge, J.R. Structures of human plasma β-factor XIIa cocrystallized with potent inhibitors. Blood Adv., 2018, 2(5), 549-558.
[http://dx.doi.org/10.1182/bloodadvances.2018016337] [PMID: 29519898]
[50]
Kar, S.; Bankston, P.; Afosah, D.K.; Al-Horani, R.A. Lignosulfonic acid sodium is a noncompetitive inhibitor of human factor XIa. Pharmaceuticals, 2021, 14(9), 886.
[http://dx.doi.org/10.3390/ph14090886] [PMID: 34577586]
[51]
Al-Horani, R.A.; Aliter, K.F.; Kar, S.; Mottamal, M. Sulfonated nonsaccharide heparin mimetics are potent and noncompetitive inhibitors of human neutrophil elastase. ACS Omega, 2021, 6(19), 12699-12710.
[http://dx.doi.org/10.1021/acsomega.1c00935] [PMID: 34056422]
[52]
Kar, S.; Mottamal, M.; Al-Horani, R.A. Discovery of benzyl tetraphosphonate derivative as inhibitor of human factor xia. ChemistryOpen, 2020, 9(11), 1161-1172.
[http://dx.doi.org/10.1002/open.202000277] [PMID: 33204588]
[53]
Al-Horani, R.A.; Clemons, D.; Mottamal, M. The in vitro effects of pentamidine isethionate on coagulation and fibrinolysis. Molecules, 2019, 24(11), 2146.
[http://dx.doi.org/10.3390/molecules24112146] [PMID: 31174390]
[54]
Obaidullah, A.J.; Al-Horani, R.A. Discovery of chromen-7-yl furan-2-carboxylate as a potent and selective factor Xia inhibitor. Cardiovasc. Hematol. Agents Med. Chem., 2017, 15(1), 40-48.
[PMID: 28552062]
[55]
Boothello, R.S.; Al-Horani, R.A.; Desai, U.R. Glycosaminoglycan-protein interaction studies using fluorescence spectroscopy. Methods Mol. Biol., 2015, 1229, 335-353.
[http://dx.doi.org/10.1007/978-1-4939-1714-3_27] [PMID: 25325964]
[56]
Gailani, D; Smith, SB Structural and functional features of factor XI. J Thromb. Haemost., 2009, 7(Suppl. 1), 75-78.
[57]
Geng, Y.; Verhamme, I.M.; Smith, S.A.; Cheng, Q.; Sun, M.; Sheehan, J.P.; Morrissey, J.H.; Gailani, D. Factor XI anion-binding sites are required for productive interactions with polyphosphate. J. Thromb. Haemost., 2013, 11(11), 2020-2028.
[http://dx.doi.org/10.1111/jth.12414] [PMID: 24118982]
[58]
Cohen, A.T.; Harrington, R.A.; Goldhaber, S.Z.; Hull, R.D.; Wiens, B.L.; Gold, A.; Hernandez, A.F.; Gibson, C.M. APEX Investigators. Extended thromboprophylaxis with betrixaban in acutely Ill medical patients. N. Engl. J. Med., 2016, 375(6), 534-544.
[http://dx.doi.org/10.1056/NEJMoa1601747] [PMID: 27232649]
[59]
Schulman, S.; Kakkar, A.K.; Goldhaber, S.Z.; Schellong, S.; Eriksson, H.; Mismetti, P.; Christiansen, A.V.; Friedman, J.; Le Maulf, F.; Peter, N.; Kearon, C. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation, 2014, 129(7), 764-772.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.113.004450] [PMID: 24344086]
[60]
Agnelli, G.; Buller, H.R.; Cohen, A.; Curto, M.; Gallus, A.S.; Johnson, M.; Masiukiewicz, U.; Pak, R.; Thompson, J.; Raskob, G.E.; Weitz, J.I. Oral apixaban for the treatment of acute venous thromboembolism. N. Engl. J. Med., 2013, 369(9), 799-808.
[http://dx.doi.org/10.1056/NEJMoa1302507] [PMID: 23808982]
[61]
Büller, H.R.; Décousus, H.; Grosso, M.A.; Mercuri, M.; Middeldorp, S.; Prins, M.H.; Raskob, G.E.; Schellong, S.M.; Schwocho, L.; Segers, A.; Shi, M.; Verhamme, P.; Wells, P. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N. Engl. J. Med., 2013, 369(15), 1406-1415.
[http://dx.doi.org/10.1056/NEJMoa1306638] [PMID: 23991658]
[62]
Alamneh, E.A.; Chalmers, L.; Bereznicki, L.R. Suboptimal use of oral anticoagulants in atrial fibrillation: Has the introduction of direct oral anticoagulants improved prescribing practices? Am. J. Cardiovasc. Drugs, 2016, 16(3), 183-200.
[http://dx.doi.org/10.1007/s40256-016-0161-8] [PMID: 26862063]
[63]
Lutz, J.; Jurk, K.; Schinzel, H. Direct oral anticoagulants in patients with chronic kidney disease: Patient selection and special considerations. Int. J. Nephrol. Renovasc. Dis., 2017, 10, 135-143.
[http://dx.doi.org/10.2147/IJNRD.S105771] [PMID: 28652799]
[64]
Black-Maier, E.; Piccini, J.P. Oral anticoagulation in end-stage renal disease and atrial fibrillation: Is it time to just say no to drugs? Heart, 2017, 103(11), 807-808.
[http://dx.doi.org/10.1136/heartjnl-2016-310540] [PMID: 28069637]
[65]
Heine, G.H.; Brandenburg, V. Anticoagulation, atrial fibrillation, and chronic kidney disease-whose side are you on? Kidney Int., 2017, 91(4), 778-780.
[http://dx.doi.org/10.1016/j.kint.2016.11.028] [PMID: 28314578]
[66]
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]

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