6-(Arylaminomethyl) Isoquinolines as Enzyme Inhibitors and Their Preparation:
A Patent Highlight of Factor XIIa Inhibitors

Rami   A.   Al-Horani
doi:10.2174/1871525721666230126114224
Keywords: Isoquinolines, factor XIIa, anticoagulants, clotting, enzyme inhibitors.
« Previous Next »
Graphical Abstract

[1]
Ivanov, I.; Matafonov, A.; Sun, M.; Cheng, Q.; Dickeson, S.K.; Verhamme, I.M.; Emsley, J.; Gailani, D. Proteolytic properties of single-chain factor XII: A mechanism for triggering contact activation. Blood,  2017, 129(11), 1527-1537.
 [http://dx.doi.org/10.1182/blood-2016-10-744110] [PMID:  28069606]

[2]
Pathak, M.; Manna, R.; Li, C.; Kaira, B.G.; Hamad, B.K.; Belviso, B.D.; Bonturi, C.R.; Dreveny, I.; Fischer, P.M.; Dekker, L.V.; Oliva, M.L.V.; Emsley, J. Crystal structures of the recombinant β-factor XIIa protease with bound Thr-Arg and Pro-Arg substrate mimetics. Acta Crystallogr. D Struct. Biol.,  2019, 75(6), 578-591.
 [http://dx.doi.org/10.1107/S2059798319006910] [PMID:  31205020]

[3]
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]

[4]
Fischer, P.M. Design of small-molecule active-site inhibitors of the S1A family proteases as procoagulant and anticoagulant drugs. J. Med. Chem.,  2018, 61(9), 3799-3822.
 [http://dx.doi.org/10.1021/acs.jmedchem.7b00772] [PMID:  29072911]

[5]
Hamad, B.K.; Pathak, M.; Manna, R.; Fischer, P.M.; Emsley, J.; Dekker, L.V. Assessment of the protein interaction between coagulation factor XII and corn trypsin inhibitor by molecular docking and biochemical validation. J. Thromb. Haemost.,  2017, 15(9), 1818-1828.
 [http://dx.doi.org/10.1111/jth.13773] [PMID:  28688220]

[6]
Göbel, K.; Asaridou, C.M.; Merker, M.; Eichler, S.; Herrmann, A.M.; Geuß, E.; Ruck, T.; Schüngel, L.; Groeneweg, L.; Narayanan, V.; Schneider-Hohendorf, T.; Gross, C.C.; Wiendl, H.; Kehrel, B.E.; Kleinschnitz, C.; Meuth, S.G. Plasma kallikrein modulates immune cell trafficking during neuroinflammation via PAR2 and bradykinin release. Proc. Natl. Acad. Sci. USA,  2019, 116(1), 271-276.
 [http://dx.doi.org/10.1073/pnas.1810020116] [PMID:  30559188]

[7]
Abdallah, R.T.; Keum, J.S.; Lee, M-H.; Wang, B.; Gooz, M.; Luttrell, D.K.; Luttrell, L.M.; Jaffa, A.A.; Jaffa, A.A. Plasma kallikrein promotes epidermal growth factor receptor transactivation and signaling in vascular smooth muscle through direct activation of protease-activated receptors. J. Biol. Chem.,  2010, 285(45), 35206-35215.
 [http://dx.doi.org/10.1074/jbc.M110.171769] [PMID:  20826789]

[8]
Konings, J.; Hoving, L.R.; Ariëns, R.S.; Hethershaw, E.L.; Ninivaggi, M.; Hardy, L.J.; de Laat, B.; ten Cate, H.; Philippou, H.; Govers-Riemslag, J.W.P. The role of activated coagulation factor XII in overall clot stability and fibrinolysis. Thromb. Res.,  2015, 136(2), 474-480.
 [http://dx.doi.org/10.1016/j.thromres.2015.06.028] [PMID:  26153047]

[9]
Abid, K.; Rochat, B.; Lassahn, P.G.; Stöcklin, R.; Michalet, S.; Brakch, N.; Aubert, J.F.; Vatansever, B.; Tella, P.; De Meester, I.; Grouzmann, E. Kinetic study of neuropeptide Y (NPY) proteolysis in blood and identification of NPY3-35: A new peptide generated by plasma kallikrein. J. Biol. Chem.,  2009, 284(37), 24715-24724.
 [http://dx.doi.org/10.1074/jbc.M109.035253] [PMID:  19620246]

[10]
Kaplan, A.P.; Joseph, K. Pathogenic mechanisms of bradykinin mediated diseases: dysregulation of an innate inflammatory pathway. Adv. Immunol.,  2014, 121, 41-89.
 [http://dx.doi.org/10.1016/B978-0-12-800100-4.00002-7] [PMID:  24388213]

[11]
Hopp, S.; Nolte, M.W.; Stetter, C.; Kleinschnitz, C.; Sirén, A.L.; Albert-Weissenberger, C. Alleviation 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]

[12]
 A study to investigate CSL312 in Subject with Hereditary Angioedema Available from: https://clinicaltrials.gov/ct2/show/NCT03712228?cond=NCT03712228&draw=1&rank=1

[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]
de Maat, S.; Björkqvist, J.; Suffritti, C.; Wiesenekker, C.P.; Nagtegaal, W.; Koekman, A.; van Dooremalen, S.; Pasterkamp, G.; de Groot, P.G.; Cicardi, M.; Renné, T.; Maas, C. Plasmin is a natural trigger for bradykinin production in patients with hereditary angioedema with factor XII mutations. J. Allergy Clin. Immunol.,  2016, 138(5), 1414-1423.e9.
 [http://dx.doi.org/10.1016/j.jaci.2016.02.021] [PMID:  27130860]

[15]
Veronez, C.L.; Aabom, A.; Martin, R.P.; Filippelli-Silva, R.; Gonçalves, R.F.; Nicolicht, P.; Mendes, A.R.; Da Silva, J.; Guilarte, M.; Grumach, A.S.; Mansour, E.; Bygum, A.; Pesquero, J.B. Genetic variation of kallikrein-kinin system and related genes in patients with hereditary angioedema. Front. Med. (Lausanne),  2019, 6, 28.
 [http://dx.doi.org/10.3389/fmed.2019.00028] [PMID:  30847342]

[16]
Recke, A.; Massalme, E.G.; Jappe, U.; Steinmüller-Magin, L.; Schmidt, J.; Hellenbroich, Y.; Hüning, I.; Gillessen-Kaesbach, G.; Zillikens, D.; Hartmann, K. Identification of the recently described plasminogen gene mutation p.Lys330Glu in a family from Northern Germany with hereditary angioedema. Clin. Transl. Allergy,  2019, 9(1), 9.
 [http://dx.doi.org/10.1186/s13601-019-0247-x] [PMID:  30809376]

[17]
Mansi, M.; Zanichelli, A.; Coerezza, A.; Suffritti, C.; Wu, M.A.; Vacchini, R.; Stieber, C.; Cichon, S.; Cicardi, M. Presentation, diagnosis and treatment of angioedema without wheals: a retrospective analysis of a cohort of 1058 patients. J. Intern. Med.,  2015, 277(5), 585-593.
 [http://dx.doi.org/10.1111/joim.12304] [PMID:  25196353]

[18]
de Maat, S.; Clark, C.C.; Boertien, M.; Parr, N.; Sanrattana, W.; Hofman, Z.L.M.; Maas, C. Factor XII truncation accelerates activation in solution. J. Thromb. Haemost.,  2019, 17(1), 183-194.
 [http://dx.doi.org/10.1111/jth.14325] [PMID:  30394658]

[19]
Kedarisetty, S.; Jones, E.; Tint, D.; Soliman, A.M.S. Air pollution and angioedema. Otolaryngol. Head Neck Surg.,  2019, 161(3), 431-438.
 [http://dx.doi.org/10.1177/0194599819846446] [PMID:  31038389]

[20]
Long, Y.M.; Zhao, X.C.; Clermont, A.C.; Zhou, Q.F.; Liu, Q.; Feener, E.P.; Yan, B.; Jiang, G.B. Negatively charged silver nanoparticles cause retinal vascular permeability by activating plasma contact system and disrupting adherens junction. Nanotoxicology,  2016, 10(4), 501-511.
 [http://dx.doi.org/10.3109/17435390.2015.1088589] [PMID:  26399585]

[21]
Baş, M.; Hoffmann, T.K.; Kojda, G. Icatibant in ACE-inhibitor-induced angioedema. N. Engl. J. Med.,  2015, 372(19), 1867-1868.
 [PMID:  25946291]

[22]
Leibfried, M.; Kovary, A. C1 Esterase Inhibitor (Berinert) for ACE inhibitor-induced angioedema: two case reports. J. Pharm. Pract.,  2017, 30(6), 668-671.
 [http://dx.doi.org/10.1177/0897190016677427] [PMID:  27837046]

[23]
van den Elzen, M.; Go, M.F.C.L.; Knulst, A.C.; Blankestijn, M.A.; van Os-Medendorp, H.; Otten, H.G. Efficacy of treatment of non-hereditary angioedema. Clin. Rev. Allergy Immunol.,  2018, 54(3), 412-431.
 [http://dx.doi.org/10.1007/s12016-016-8585-0] [PMID:  27672078]

[24]
Han, E.D.; MacFarlane, R.C.; Mulligan, A.N.; Scafidi, J.; Davis, A.E. III Increased vascular permeability in C1 inhibitor–deficient mice mediated by the bradykinin type 2 receptor. J. Clin. Invest.,  2002, 109(8), 1057-1063.
 [http://dx.doi.org/10.1172/JCI200214211] [PMID:  11956243]

[25]
Simão, F.; Ustunkaya, T.; Clermont, A.C.; Feener, E.P. Plasma kallikrein mediates brain hemorrhage and edema caused by tissue plasminogen activator therapy in mice after stroke. Blood,  2017, 129(16), 2280-2290.
 [http://dx.doi.org/10.1182/blood-2016-09-740670] [PMID:  28130211]

[26]
Fröhlich, K.; Macha, K.; Gerner, S.T.; Bobinger, T.; Schmidt, M.; Dörfler, A.; Hilz, M.J.; Schwab, S.; Seifert, F.; Kallmünzer, B.; Winder, K. Angioedema in stroke patients with thrombolysis. Stroke,  2019, 50(7), 1682-1687.
 [http://dx.doi.org/10.1161/STROKEAHA.119.025260] [PMID:  31182002]

[27]
Rathbun, K.M. Angioedema after thrombolysis with tissue plasminogen activator: an airway emergency. Oxf. Med. Case Rep.,  2019, 2019(1), omy112.
 [http://dx.doi.org/10.1093/omcr/omy112] [PMID:  30697429]

[28]
Lekoubou, A.; Philippeau, F.; Derex, L.; Olaru, A.; Gouttard, M.; Vieillart, A.; Kengne, A.P. Audit report and systematic review of orolingual angioedema in post-acute stroke thrombolysis. Neurol. Res.,  2014, 36(7), 687-694.
 [http://dx.doi.org/10.1179/1743132813Y.0000000302] [PMID:  24620962]

[29]
Hill, M.D.; Lye, T.; Moss, H.; Barber, P.A.; Demchuk, A.M.; Newcommon, N.J.; Green, T.L.; Kenney, C.; Cole-Haskayne, A.; Buchan, A.M. Hemi-orolingual angioedema and ACE inhibition after alteplase treatment of stroke. Neurology,  2003, 60(9), 1525-1527.
 [http://dx.doi.org/10.1212/01.WNL.0000058840.66596.1A] [PMID:  12743244]

[30]
Stone, C., Jr; Brown, N.J. Angiotensin-converting enzyme inhibitor and other drug-associated angioedema. Immunol. Allergy Clin. North Am.,  2017, 37(3), 483-495.
 [http://dx.doi.org/10.1016/j.iac.2017.04.006] [PMID:  28687104]

[31]
Scott, S.I.; Andersen, M.F.; Aagaard, L.; Buchwald, C.V.; Rasmussen, E.R. Dipeptidyl Peptidase-4 inhibitor induced angioedema - an overlooked adverse drug reaction? Curr. Diabetes Rev.,  2018, 14(4), 327-333.
 [http://dx.doi.org/10.2174/1573399813666170214113856] [PMID:  28201967]

[32]
Hermanrud, T.; Bygum, A.; Rasmussen, E.R. Recurrent angioedema associated with pharmacological inhibition of dipeptidyl peptidase IV. BMJ Case Rep.,  2017, 2017, bcr2016217802.
 [http://dx.doi.org/10.1136/bcr-2016-217802] [PMID:  28073873]

[33]
Kim, H.; Baik, S.Y.; Yang, S.J.; Kim, T.M.; Lee, S.H.; Cho, J.H.; Choi, I.Y.; Kim, J.H.; Yoon, K.H.; Kim, H.S. Clinical experiences and case review of angiotensin II receptor blocker-related angioedema in Korea. Basic Clin. Pharmacol. Toxicol.,  2019, 124(1), 115-122.
 [http://dx.doi.org/10.1111/bcpt.13097] [PMID:  30003686]

[34]
Reichman, M.E.; Wernecke, M.; Graham, D.J.; Liao, J.; Yap, J.; Chillarige, Y.; Southworth, M.R.; Keeton, S.; Goulding, M.R.; Mott, K.; Kelman, J.A. Antihypertensive drug associated angioedema: effect modification by race/ethnicity. Pharmacoepidemiol. Drug Saf.,  2017, 26(10), 1190-1196.
 [http://dx.doi.org/10.1002/pds.4260] [PMID:  28722207]

[35]
Diestro, J.D.B.; Sedano, L.S.P.; Reyes, N.G.D.; San Jose, M.C.Z. Hemilingual angioedema after thrombolysis in a patient on an angiotensin II receptor blocker. J. Stroke Cerebrovasc. Dis.,  2019, 28(5), e44-e45.
 [http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2019.01.030] [PMID:  30772164]

[36]
Giard, C.; Nicolie, B.; Drouet, M.; Lefebvre-Lacoeuille, C.; Le Sellin, J.; Bonneau, J.C.; Maillard, H.; Rénier, G.; Cichon, S.; Ponard, D.; Drouet, C.; Martin, L. Angio-oedema induced by oestrogen contraceptives is mediated by bradykinin and is frequently associated with urticaria. Dermatology,  2012, 225(1), 62-69.
 [http://dx.doi.org/10.1159/000340029] [PMID:  22922353]

[37]
Liu, J.; Feener, E.P. Plasma kallikrein-kinin system and diabetic retinopathy. bchm,  2013, 394(3), 319-328.
 [http://dx.doi.org/10.1515/hsz-2012-0316] [PMID: 23362193]

[38]
Gao, B.B.; Clermont, A.; Rook, S.; Fonda, S.J.; Srinivasan, V.J.; Wojtkowski, M.; Fujimoto, J.G.; Avery, R.L.; Arrigg, P.G.; Bursell, S.E.; Aiello, L.P.; Feener, E.P. Extracellular carbonic anhydrase mediates hemorrhagic retinal and cerebral vascular permeability through prekallikrein activation. Nat. Med.,  2007, 13(2), 181-188.
 [http://dx.doi.org/10.1038/nm1534] [PMID:  17259996]

[39]
Gao, B.B.; Chen, X.; Timothy, N.; Aiello, L.P.; Feener, E.P. Characterization of the vitreous proteome in diabetes without diabetic retinopathy and diabetes with proliferative diabetic retinopathy. J. Proteome Res.,  2008, 7(6), 2516-2525.
 [http://dx.doi.org/10.1021/pr800112g] [PMID:  18433156]

[40]
Kita, T.; Clermont, A.C.; Murugesan, N.; Zhou, Q.; Fujisawa, K.; Ishibashi, T.; Aiello, L.P.; Feener, E.P. Plasma kallikrein-kinin system as a VEGF-independent mediator of diabetic macular edema. Diabetes,  2015, 64(10), 3588-3599.
 [http://dx.doi.org/10.2337/db15-0317] [PMID:  25979073]

[41]
Clermont, A.; Murugesan, N.; Zhou, Q.; Kita, T.; Robson, P.A.; Rushbrooke, L.J.; Evans, D.M.; Aiello, L.P.; Feener, E.P. Plasma kallikrein mediates vascular endothelial growth factor–induced retinal dysfunction and thickening. Invest. Ophthalmol. Vis. Sci.,  2016, 57(6), 2390-2399.
 [http://dx.doi.org/10.1167/iovs.15-18272] [PMID:  27138737]

[42]
Morrison, D.C.; Cochrane, C.G. Direct evidence for Hageman factor (factor XII) activation by bacterial lipopolysaccharides (endotoxins). J. Exp. Med.,  1974, 140(3), 797-811.
 [http://dx.doi.org/10.1084/jem.140.3.797] [PMID:  4378413]

[43]
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]

[44]
Simões, P.S.R.; Zanelatto, A.O.; Assis, M.C.; Varella, P.P.V.; Yacubian, E.M.; Carrete, H.; Centeno, R.; Araujo, M.S.; Cavalheiro, E.A.; Tersariol, I.L.S.; Motta, G.; Naffah-Mazzacoratti, M.G. Plasma kallikrein‐kinin system contributes to peripheral inflammation in temporal lobe epilepsy. J. Neurochem.,  2019, 150(3), 296-311.
 [http://dx.doi.org/10.1111/jnc.14793] [PMID:  31206169]

[45]
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]

[46]
 Efficacy and safety of 10NIS-PKKRx for preventive treatment of chronić migraine Available from: https://clinicaltrials.gov/ct2/show/NCT03108469?cond=NCT03108469&draw=2&rank=1

[47]
Bender, L.; Weidmann, H.; Rose-John, S.; Renné, T.; Long, A.T. Factor XII-Driven inflammatory reactions with implications for anaphylaxis. Front. Immunol.,  2017, 8, 1115.
 [http://dx.doi.org/10.3389/fimmu.2017.01115] [PMID:  28966616]

[48]
Sala-Cunill, A.; Björkqvist, J.; Senter, R.; Guilarte, M.; Cardona, V.; Labrador, M.; Nickel, K.F.; Butler, L.; Luengo, O.; Kumar, P.; Labberton, L.; Long, A.; Di Gennaro, A.; Kenne, E.; Jämsä, A.; Krieger, T.; Schlüter, H.; Fuchs, T.; Flohr, S.; Hassiepen, U.; Cumin, F.; McCrae, K.; Maas, C.; Stavrou, E.; Renné, T. Plasma contact system activation drives anaphylaxis in severe mast cell–mediated allergic reactions. J. Allergy Clin. Immunol.,  2015, 135(4), 1031-1043.e6.
 [http://dx.doi.org/10.1016/j.jaci.2014.07.057] [PMID:  25240785]

[49]
Davie, E.W.; Ratnoff, O.D. Waterfall sequence for intrinsic blood clotting. Science,  1964, 145(3638), 1310-1312.
 [http://dx.doi.org/10.1126/science.145.3638.1310] [PMID:  14173416]

[50]
Radcliffe, R.; Bagdasarian, A.; Colman, R.; Nemerson, Y. Activation of bovine factor VII by hageman factor fragments. Blood,  1977, 50(4), 611-617.
 [http://dx.doi.org/10.1182/blood.V50.4.611.611] [PMID:  561632]

[51]
Puy, C.; Tucker, E.I.; Wong, Z.C.; Gailani, D.; Smith, S.A.; Choi, S.H.; Morrissey, J.H.; Gruber, A.; McCarty, O.J.T. Factor XII promotes blood coagulation independent of factor XI in the presence of long-chain polyphosphates. J. Thromb. Haemost.,  2013, 11(7), 1341-1352.
 [http://dx.doi.org/10.1111/jth.12295] [PMID:  23659638]

[52]
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]

[53]
Simão, F.; Feener, E.P. The effects of the contact activation system on hemorrhage. Front. Med. (Lausanne),  2017, 4, 121.
 [http://dx.doi.org/10.3389/fmed.2017.00121] [PMID:  28824910]

[54]
Worm, M.; Köhler, E.C.; Panda, R.; Long, A.; Butler, L.M.; Stavrou, E.X.; Nickel, K.F.; Fuchs, T.A.; Renné, T. The factor XIIa blocking antibody 3F7: a safe anticoagulant with anti-inflammatory activities. Ann. Transl. Med.,  2015, 3(17), 247.
 [PMID:  26605293]

[55]
Barbieri, C.M.; Wang, X.; Wu, W.; Zhou, X.; Ogawa, A.M.; O’Neill, K.; Chu, D.; Castriota, G.; Seiffert, D.A.; Gutstein, D.E.; Chen, Z. Factor XIIa as a novel target for thrombosis: target engagement requirement and efficacy in a rabbit model of microembolic signals. J. Pharmacol. Exp. Ther.,  2017, 360(3), 466-475.
 [http://dx.doi.org/10.1124/jpet.116.238493] [PMID:  28035006]

[56]
Krupka, J.; May, F.; Weimer, T.; Pragst, I.; Kleinschnitz, C.; Stoll, G.; Panousis, C.; Dickneite, G.; Nolte, M.W. The coagulation factor XIIa inhibitor rHA-Infestin-4 improves outcome after cerebral ischemia/reperfusion injury in rats. PLoS One,  2016, 11(1), e0146783.
 [http://dx.doi.org/10.1371/journal.pone.0146783] [PMID:  26815580]

[57]
Leung, P.Y.; Hurst, S.; Berny-Lang, M.A.; Verbout, N.G.; Gailani, D.; Tucker, E.I.; Wang, R.K.; McCarty, O.J.T.; Gruber, A. Inhibition of Factor XII-mediated activation of factor XI provides protection against experimental acute ischemic stroke in mice. Transl. Stroke Res.,  2012, 3(3), 381-389.
 [http://dx.doi.org/10.1007/s12975-012-0186-5] [PMID:  23634198]

[58]
Gailani, D. Making thrombolysis safer in stroke. Blood,  2017, 129(16), 2212-2213.
 [http://dx.doi.org/10.1182/blood-2017-02-765610] [PMID:  28428237]

[59]
Liu, J.; Gao, B.B.; Clermont, A.C.; Blair, P.; Chilcote, T.J.; Sinha, S.; Flaumenhaft, R.; Feener, E.P. Hyperglycemia-induced cerebral hematoma expansion is mediated by plasma kallikrein. Nat. Med.,  2011, 17(2), 206-210.
 [http://dx.doi.org/10.1038/nm.2295] [PMID:  21258336]

[60]
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]

[61]
Rao, Factor XIIa Inhibitors. WO2018/093695, 2020.

[62]
Hicks, Factor Xlla Inhibitors. WO2018/093716, 2019.

[63]
Breslow. Aminotriazole immunomodulators for treating autoimmune diseases. WO2017/123518, 2014.

[64]
Ponda, Aminacylindazole immunomodulators for treatment of autoimmune diseases. WO2017/205296, 2014.

[65]
Pyranopyrazole and pyrazolopyridine immunomodulators for treatment of autoimmune diseases. WO2019/108565, 2018.

[66]
Nolte, Factor XII inhibitors for the administration with medical procedures comprising contact with artificial surfaces. W02012/120128, 2015.

[67]
Shori, D.K.; Proctor, G.B.; Chao, J.; Ka-Ming, C.; Garrett, J.R. New specific assays for tonin and tissue kallikrein activities in rat submandibular glands. Biochem. Pharmacol.,  1992, 43(6), 1209-1217.
 [http://dx.doi.org/10.1016/0006-2952(92)90494-4] [PMID:  1314057]

[68]
Baeriswyl, V.; Calzavarini, S.; Chen, S.; Zorzi, A.; Bologna, L.; Angelillo-Scherrer, A.; Heinis, C. A synthetic factor XIIa inhibitor blocks selectively intrinsic coagulation initiation. ACS Chem. Biol.,  2015, 10(8), 1861-1870.
 [http://dx.doi.org/10.1021/acschembio.5b00103] [PMID:  25989088]

[69]
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]
Rights & Permissions Print Cite
Article Metrics
14
1
Journal Information
For Authors
For Editors
For Reviewers
Explore Articles
Open Access
Open Access Articles
For Visitors
DOI https://dx.doi.org/10.2174/1871525721666230126114224	Print ISSN 1871-5257
Publisher Name Bentham Science Publisher	Online ISSN 1875-6182
Cardiovascular & Hematological Agents in Medicinal Chemistry

6-(Arylaminomethyl) Isoquinolines as Enzyme Inhibitors and Their Preparation: A Patent Highlight of Factor XIIa Inhibitors

Graphical Abstract

Related Journals

Related Books

Related Articles
