Discovery methodology for the development of direct factor VIIa inhibitors

Expert Opinion on Drug Discovery

Volumn 9, Issue 8, 2014, Pages 859-872

  Henry, Brian L ^a   Desai, Umesh R ^b  

^a UNIVERSITY OF PITTSBURGH MEDICAL CENTER   (United States)

^b VIRGINIA COMMONWEALTH UNIVERSITY   (United States)

Author keywords

Anticoagulants; Coagulation; Factor VIIa; Small molecule inhibitors; Tissue factor

Indexed keywords

AMIDINE; ANTICOAGULANT AGENT; BENZIMIDAZOLE DERIVATIVE; BENZOTHIAZEPINE DERIVATIVE; BIPHENYL DERIVATIVE; BLOOD CLOTTING FACTOR 10A INHIBITOR; BLOOD CLOTTING FACTOR 7A; BLOOD CLOTTING FACTOR 7A INHIBITOR; CARBOXYLIC ACID DERIVATIVE; HEMEXTIN AB; PEPTIDOMIMETIC AGENT; PHENYLPYRUVIC ACID; PRODRUG; RECOMBINANT NEMATODE ANTICOAGULANT PROTEIN C2; SERINE PROTEINASE INHIBITOR; SULFONAMIDE; THROMBIN INHIBITOR; UNCLASSIFIED DRUG; 1,5-BENZOTHIAZEPINE; THIAZEPINE DERIVATIVE;

BLEEDING; DRUG BIOAVAILABILITY; DRUG SELECTIVITY; HUMAN; METHODOLOGY; NONHUMAN; PHAGE DISPLAY; PRIORITY JOURNAL; REVIEW; RISK ASSESSMENT; STRUCTURE ACTIVITY RELATION; ANIMAL; ANTAGONISTS AND INHIBITORS; BIOAVAILABILITY; CHEMICALLY INDUCED; CHEMISTRY; COMPARATIVE STUDY; DRUG DESIGN;

ANIMALS; ANTICOAGULANTS; BIOLOGICAL AVAILABILITY; DRUG DESIGN; FACTOR VIIA; HEMORRHAGE; HUMANS; THIAZEPINES;

EID: 84904794902     PISSN: 17460441     EISSN: 1746045X     Source Type: Journal    
DOI: 10.1517/17460441.2014.923398     Document Type: Review

References (59)

1. Macfarlane RG. An enzyme cascade in the blood clotting mechanism, and its function as a biochemical amplifier. Nature 1964;202:498-9
2. Davie EW, Ratnoff OD. Waterfall sequence for intrinsic blood clotting. Science 1964;145:1310-12
3. McMichael M. New models of hemostasis. Top Companion Anim Med 2012;27:40-5
4. Hoffman M. A cell-based model of coagulation and the role of factor VIIa. Blood Rev 2003;17:S1-5
5. Wolberg AS, Mast AE. Tissue factor and factor VIIa-hemostasis and beyond. Thromb Res 2012;129(Suppl 2):S1-4
6. Murray CJ, Lopez AD. Mortality by cause for eight regions of the world: global Burden of Disease Study. Lancet 1997;349:1269-76
7. Cushman M, Tsai AW, White RH, et al. Deep vein thrombosis and pulmonary embolism in two cohorts: the longitudinal investigation of thromboembolism etiology. Am J Med 2004;117:19-25
8. Naccarelli GV, Varker H, Lin J, Schulman KL. Increasing prevalence of atrial fibrillation and flutter in the United States. Am J Cardiol 2009;104:1534-9
9. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 1991;22:983-8
10. Ruf W. Tissue factor and cancer. Thromb Res 2012;130(Suppl 1):S84-7
11. McLean J. The thromboplastic action of cephalin. Am J Physiol 1916;41:250-7
12. Stahmann MA, Huebner CF, Link KP. Studies on the hemorrhagic sweet clover disease. V. Identification and synthesis of the hemorrhagic agent. J Biol Chem 1941;138:513-27
13. Di Nisio M, Middeldorp S, Büller HR. Direct thrombin inhibitors. N Engl J Med 2005;353:1028-40
14. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009;361:1139-51
15. Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011;365:883-91
16. Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011;365:981-92
17. Smith GP, Petrenko VA. Phage Display. Chem Rev 1997;97:391-410
18. Dennis MS, Eigenbrot C, Skelton NJ, et al. Peptide exosite inhibitors of factor VIIa as anticoagulants. Nature 2000;404:465-70
19. Dennis MS, Roberge M, Quan C, Lazarus RA. Selection and characterization of a new class of peptide exosite inhibitors of coagulation factor VIIa. Biochemistry 2001;40:9513-21
20. Roberge M, Santell L, Dennis MS, et al. A novel exosite on coagulation factor VIIa and its molecular interactions with a new class of peptide inhibitors. Biochemistry 2001;40:9522-31
21. Eigenbrot C, Kirchhofer D, Dennis MS, et al. The factor VII zymogen structure reveals reregistration of beta strands during activation. Structure 2001;9:627-36
22. Lowman HB. Bacteriophage display and discovery of peptide leads for drug development. Annu Rev Biophys Biomol Struct 1997;26:401-24
23. Stassens P, Bergum PW, Gansemans Y, et al. Anticoagulant repertoire of the hookworm Ancylostoma caninum. Proc Natl Acad Sci USA 1996;93:2149-54
24. Bergum PW, Cruikshank A, Maki SL, et al. Role of zymogen and activated factor X as scaffolds for the inhibition of the blood coagulation factor VIIa-tissue factor complex by recombinant nematode anticoagulant protein c2. J Biol Chem 2001;276:10063-71
25. Buddai SK, Toulokhonova L, Bergum PW, et al. Nematode anticoagulant protein c2 reveals a site on factor Xa that is important for macromolecular substrate binding to human prothrombinase. J Biol Chem 2002;277:26689-98
26. Lee AYY, Vlasuk GP. Recombinant nematode anticoagulant protein c2 and other inhibitors targeting blood coagulation fact or VIIa/tissue factor. J Intern Med 2003;254:313-21
27. Giugliano RP, Wiviott SD, Stone PH, et al. Recombinant nematode anticoagulant protein c2 in patients with non-ST-segment elevation acute coronary syndrome: the ANTHEM-TIMI-32 trial. J Am Coll Cardiol 2007;49:2398-407
28. Moons AH, Peters RJ, Bijsterveld NR, et al. Recombinant nematode anticoagulant protein c2, an inhibitor of the tissue factor/factor VIIa complex, in patients undergoing elective coronary angioplasty. J Am Coll Cardiol 2003;41:2147-53
29. Banerjee Y, Mizuguchi J, Iwanaga S, Kini RM. Hemextin AB complex, a unique anticoagulant protein complex from Hemachatus haemachatus (African Ringhals cobra) venom that inhibits clot initiation and factor VIIa activity. J Biol Chem 2005;280:42601-11
30. Banerjee Y, Mizuguchi J, Iwanaga S, Kini RM. Hemextin AB complex-a snake venom anticoagulant protein complex that inhibits factor VIIa activity. Pathophysiol Haemost Thromb 2005;34:184-7
31. Banerjee Y, Lakshminarayanan R, Vivekanandan S, et al. Biophysical characterization of anticoagulant hemextin AB complex from the venom of snake Hemachatus haemachatus. Biophys J 2007;93:3963-76
32. Bariwal JB, Upadhyay KD, Manvar AT, et al. 1, 5-Benzothiazepine, a versatile pharmacophore: a review. Eur J Med Chem 2008;43:2279-90
33. Ayral E, Gloanec P, Bergé G, et al. Design, synthesis, and biological evaluation of 1, 5-benzothiazepine-4-one derivatives targeting factor VIIa/tissue factor. Bioorg Med Chem Lett 2009;19:1386-91
34. Shrader WD, Kolesnikov A, Burgess-Henry J, et al. Factor VIIa inhibitors: gaining selectivity within the trypsin family. Bioorg Med Chem Lett 2006;16:1596-600
35. Sichler K, Banner DW, D'Arcy A, et al. Crystal structures of uninhibited factor VIIa link its cofactor and substrate-assisted activation to specific interactions. J Mol Biol 2002;322:591-603
36. Sagi K, Fujita K, Sugiki M, et al. Optimization of a coagulation factor VIIa inhibitor found in factor Xa inhibitor library. Bioorg Med Chem 2005;13:1487-96
37. Shiraishi T, Kadono S, Haramura M, et al. Factor VIIa inhibitors: target hopping in the serine protease family using X-ray structure determination. Bioorg Med Chem Lett 2008;18:4533-7
38. Parlow JJ, Dice TA, Lachance RM, et al. Polymer-assisted solution-phase library synthesis and crystal structure of alpha-ketothiazoles as tissue factor VIIa inhibitors. J Med Chem 2003;46:4043-9
39. South MS, Case BL, Wood RS, et al. Structure-based drug design of pyrazinone antithrombotics as selective inhibitors of the tissue factor VIIa complex. Bioorg Med Chem Lett 2003;13:2319-25
40. Parlow JJ, Case BL, Dice TA, et al. Design, parallel synthesis, and crystal structures of pyrazinone antithrombotics as selective inhibitors of the tissue factor VIIa complex. J Med Chem 2003;46:4050-62
41. South MS, Dice TA, Girard TJ, et al. Polymer-assisted solution-phase (PASP) parallel synthesis of an alpha-ketothiazole library as tissue factor VIIa inhibitors. Bioorg Med Chem Lett 2003;13:2363-7
42. Suleymanov OD, Szalony JA, Salyers AK, et al. Pharmacological interruption of acute thrombus formation with minimal hemorrhagic complications by a small molecule tissue factor/factor VIIa inhibitor: comparison to factor Xa and thrombin inhibition in a nonhuman primate thrombosis model. J Pharmacol Exp Ther 2003;306:1115-21
43. Kotian PL, Krishnan R, Rowland S, et al. Design, parallel synthesis, and crystal structures of biphenyl antithrombotics as selective inhibitors of tissue factor FVIIa complex. Part 1: exploration of S2 pocket pharmacophores. Bioorg Med Chem 2009;17:3934-58
44. Banner DW, D'Arcy A, Chène C, et al. The crystal structure of the complex of blood coagulation factor VIIa with soluble tissue factor. Nature 1996;380:41-6
45. Henry BL, Desai UR. Recent research developments in the direct inhibition of coagulation proteinases-inhibitors of the initiation phase. Cardiovasc Hematol Agents Med Chem 2008;6:323-36
46. Zbinden KG, Banner DW, Hilpert K, et al. Dose-dependent antithrombotic activity of an orally active tissue factor/factor VIIa inhibitor without concomitant enhancement of bleeding propensity. Bioorg Med Chem 2006;14:5357-69
47. Zbinden KG, Obst-Sander U, Hilpert K, et al. Selective and orally bioavailable phenylglycine tissue factor/factor VIIa inhibitors. Bioorg Med Chem Lett 2005;15:5344-52
48. Miura M, Seki N, Koike T, et al. Potent and selective TF/FVIIa inhibitors containing a neutral P1 ligand. Bioorg Med Chem 2006;14:7688-705
49. Miura M, Seki N, Koike T, et al. Design, synthesis and biological activity of selective and orally available TF/FVIIa complex inhibitors containing non-amidine P1 ligands. Bioorg Med Chem 2007;15:160-73
50. Bolton SA, Sutton JC, Anumula R, et al. Discovery of nonbenzamidine factor VIIa inhibitors using a biaryl acid scaffold. Bioorg Med Chem Lett 2013;23:5239-43
51. Glunz PW, Zhang X, Zou Y, et al. Nonbenzamidine acylsulfonamide tissue factor-factor VIIa inhibitors. Bioorg Med Chem Lett 2013;23:5244-8
52. Stangier J, Rathgen K, Stähle H, et al. The pharmacokinetics, pharmacodynamics, and tolerability of dabigatran etexilate, a new oral direct thrombin inhibitor, in healthy male subjects. Br J Clin Pharmacol 2007;64:292-303
53. Ruff CT, Giugliano RP, Braunwald E, et al. 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;383:955-62
54. Moreno PR. Pathophysiology of plaque disruption and thrombosis in acute ischemic syndromes. J Stroke Cerebrovasc Dis 2001;10(2 Pt 2):2-9
55. Vojacek J, Dusek J, Bis J, et al. Plasma tissue factor in coronary artery disease: further step to the understanding of the basic mechanisms of coronary artery thrombosis. Physiol Res 2008;57:1-5
56. Girard TJ, Nicholson NS. The role of tissue factor/factor VIIa in the pathophysiology of acute thrombotic formation. Curr Opin Pharmacol 2001;1:159-63
57. Artang R, Rome E, Nielsen JD, Vidaillet HJ. Meta-analysis of randomized controlled trials on risk of myocardial infarction from the use of oral direct thrombin inhibitors. Am J Cardiol 2013;112:1973-9
58. Mega JL, Braunwald E, Wiviott SD, et al. Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med 2012;366:9-19
59. Jang Y, Guzman LA, Lincoff AM, et al. Influence of blockade at specific levels of the coagulation cascade on restenosis in a rabbit atherosclerotic femoral artery injury model. Circulation 1995;92:3041-50