Chymase inhibitors for the treatment of cardiac diseases: a patent review (2010–2018)

References

• De Caterina R, Zampolli A, Del Turco S, et al. Nutritional mechanisms that influence cardiovascular disease. Am J Clin Nutr. 2006;83(2):421S–26S.
   PubMed Web of Science ®Google Scholar
• Ferrario CM. Role of angiotensin II in cardiovascular disease therapeutic implications of more than a century of research. J Renin Angiotensin Aldosterone Syst. 2006;7(1):3–14.
   PubMed Web of Science ®Google Scholar
• Oparil S, Acelajado MC, Bakris GL, et al. Hypertension. Nat Rev Dis Primers. 2018;4:18014.
   PubMed Web of Science ®Google Scholar
• Te Riet L, van Esch JH, Roks AJ, et al. Hypertension: renin-angiotensin-aldosterone system alterations. Circ Res. 2015;116(6):960–975.
   PubMed Web of Science ®Google Scholar
• Dell’Italia LJ, Collawn JF, Ferrario CM. Multifunctional role of chymase in acute and chronic tissue injury and remodeling. Circ Res. 2018;122(2):319–336.
   PubMed Web of Science ®Google Scholar
• Lundequist A, Pejler G. Biological implications of preformed mast cell mediators. Cell Mol Life Sci. 2011;68(6):965–975.
   PubMed Web of Science ®Google Scholar
• Shiota N, Rysa J, Kovanen PT, et al. A role for cardiac mast cells in the pathogenesis of hypertensive heart disease. J Hypertension. 2003;21(10):1935–1944.
   PubMed Web of Science ®Google Scholar
• Caughey GH. Mast cell tryptases and chymases in inflammation and host defense. Immunol Rev. 2007;217:141–154.
   PubMed Web of Science ®Google Scholar
• Levick SP, Melendez GC, Plante E, et al. Cardiac mast cells: the centerpiece in adverse myocardial remodeling. Cardiovascular Res. 2011;89(1):12–19.
   PubMed Web of Science ®Google Scholar
• Stewart JA, Wei CC, Brower GL, et al. Cardiac mast cell- and chymase-mediated mast cell number and matrix metalloproteinase activity and left ventricular remodeling in mitral regurgitation in the dog. J Mol Cell Cardiol. 2003;35(3):311–319.
   PubMed Web of Science ®Google Scholar
• Brower GL, Janicki JS. Pharmacologic inhibition of mast cell degranulation prevents left ventricular remodeling induced by chronic volume overload in rats. J Cardiac Fail. 2005;11(7):548–556.
   PubMed Web of Science ®Google Scholar
• Fu L, Wei CC, Powell PC, et al. Increased fibroblast chymase production mediates procollagen autophagic digestion in volume overload. J Mol Cell Cardiol. 2016;92:1–9.
   PubMed Web of Science ®Google Scholar
• Chen YW, Pat B, Gladden JD, et al. Dynamic molecular and histopathological changes in the extracellular matrix and inflammation in the transition to heart failure in isolated volume overload. Am J Physiol Heart Circ Physiol. 2011;300(6):H2251–60.
   PubMed Web of Science ®Google Scholar
• Engels W, Reiters PH, Daemen MJ, et al. Transmural changes in mast cell density in rat heart after infarct induction in vivo. J Pathol. 1995;177(4):423–429.
   PubMed Web of Science ®Google Scholar
• Patella V, de Crescenzo G, Lamparter-Schummert B, et al. Increased cardiac mast cell density and mediator release in patients with dilated cardiomyopathy. Inflamm Res. 1997;46(Suppl 1):S31–32.
   PubMedGoogle Scholar
• Levick SP, McLarty JL, Murray DB, et al. Cardiac mast cells mediate left ventricular fibrosis in the hypertensive rat heart. Hypertension. 2009;53(6):1041–1047.
   PubMed Web of Science ®Google Scholar
• Kovanen PT. Role of mast cells in atherosclerosis. Chem Immunol. 1995;62:132–170.
   PubMedGoogle Scholar
• Zhang J, Shi GP. Mast cells and metabolic syndrome. Biochem Biophys Acta. 2012;1822(1):14–20.
   PubMed Web of Science ®Google Scholar
• Patella V, de Crescenzo G, Ciccarelli A, et al. Human heart mast cells: a definitive case of mast cell heterogenecity. Int Arch Allergy Immunol. 1995;106(4):386–393.
   PubMed Web of Science ®Google Scholar
• Caughey GH. Mast cell proteases as protective and inflammatory mediators. Adv Exp Med Biol. 2011;716:212–234.
   Google Scholar
• Caughey GH, Raymond WW, Wolters PJ. Angiotensin II generation by mast cell alpha- and beta-chymases. Biochim Biophys Acta. 2000;1480(1–2):245–257.
   PubMedGoogle Scholar
• Pejler G, Abrink M, Ringvall M, et al. Mast cell proteases. Adv Immunol. 2007;95:167–255.
   PubMed Web of Science ®Google Scholar
• Pejler G, Knight SD, Henningsson F, et al. Novel insights into the biological function of mast cell carboxypeptidase A. Trends Immunol. 2009;30(8):401–408.
   PubMed Web of Science ®Google Scholar
• Sperr WR, Banki HC, Mundigler G, et al. The human cardiac mast cell: localization, isolation, phenotype, and functional characterization. Blood. 1994;84(11):3876–3884.
   PubMed Web of Science ®Google Scholar
• Ekoff M, Strasser A, Nilsson G. FcepsilonRI aggregation promotes survival of connective tissue-like mast cells but not mucosal-like mast cells. J Immunol. 2007;178(7):4177–4183.
   PubMed Web of Science ®Google Scholar
• Enerback L. Mast cells in rat gastrointestinal mucosaI. Effects of fixation. Acta Pathol Microbiol Scand. 1966;66(3):289–302.
   PubMedGoogle Scholar
• Wolters PJ, Pham CTN, Muilenburg DJ, et al. Dipeptidyl peptidase I is essential for activation of mast cell chymases, but not tryptases, in mice. J Bio Chem. 2001;276(21):18551–18556.
   PubMed Web of Science ®Google Scholar
• Ahmad S, Simmons T, Varagic J, et al. Chymase-dependent generation of angiotensin II from angiotensin-(1-12) in human atrial tissue. PLoS One. 2011;6(12):e28501.
   PubMed Web of Science ®Google Scholar
• Ahmad S, Varagic J, VonCannon JL, et al. Primacy of cardiac chymase over angiotensin converting enzyme as an angiotensin-(1-12) metabolizing enzyme. Biochem Biophys Res Commun. 2016;478(2):559–564.
   PubMed Web of Science ®Google Scholar
• Ferrario CM, Ahmad S, Nagata S, et al. An evolving story of angiotensin-II-forming pathways in rodents and humans. Clin Sci (Lond). 2014;126(7):461–469.
   PubMed Web of Science ®Google Scholar
• Soualmia F, Amri CE. Serine proteases inhibitors to treat inflammation: a patent review (2011–2016). Exp Opin Ther Patents. 2018;28(2):93–110.
   PubMed Web of Science ®Google Scholar
• Rachel KV, Sirisha GVD. Serine proteases and their inhibitors in human health and disease. Proteases in human diseases. Singapore: Springer; 2017. p. 195–226.
   Google Scholar
• Benter IF, Diz DI, Ferrario CM. Cardiovascular actions of angiotensin(1-7). Peptides. 1993;14(4):679–684.
   PubMed Web of Science ®Google Scholar
• Campagnole-Santos MJ, Diz DI, Santos RA, et al. Cardiovascular effects of angiotensin-(1–7) injected into the dorsal medulla of rats. Am J Physiol. 1989;257(1 Pt 2):H324–9.
   PubMedGoogle Scholar
• Schiavone MT, Khosla MC, Ferrario CM. Angiotensin-[1-7]: evidence for novel actions in the brain. J Cardiovasc Pharmacol. 1990;16(Suppl 4):S19–S24.
   PubMedGoogle Scholar
• Schiavone MT, Santos RA, Brosnihan KB, et al. Release of vasopressin from the rat hypothalamo-neurohypophysial system by angiotensin-(1-7) heptapeptide. Proc Natl Acad Sci U S A. 1988;85(11):4095–4098.
   PubMed Web of Science ®Google Scholar
• Ferrario CM. New physiological concepts of the renin-angiotensin system from the investigation of precursors and products of angiotensin I metabolism. Hypertension. 2010;55(2):445–452.
   PubMed Web of Science ®Google Scholar
• Welches WR, Brosnihan KB, Ferrario CM. A comparison of the properties and enzymatic activities of three angiotensin processing enzymes: angiotensin converting enzyme, prolyl endopeptidase and neutral endopeptidase. Life Sci. 1993;52(18):1461–1480.
   PubMed Web of Science ®Google Scholar
• Crackower MA, Sarao R, Oudit GY, et al. Angiotensin-converting enzyme 2 is an essential regulator of heart function. Nature. 2002;417(6891):822–828.
   PubMed Web of Science ®Google Scholar
• Nagata S, Hatakeyama K, Asami M, et al. Big angiotensin-25: a novel glycosylated angiotensin-related peptide isolated from human urine. Biochem Biophys Res Commun. 2013;441(4):757–762.
   PubMed Web of Science ®Google Scholar
• Nagata S, Kato J, Sasaki K, et al. Isolation and identification of proangiotensin-12, a possible component of the renin-angiotensin system. Biochem Biophys Res Commun. 2006;350(4):1026–1031.
   PubMed Web of Science ®Google Scholar
• Ahmad S, Varagic J, Groban L, et al. Angiotensin-(1-12): a chymase-mediated cellular angiotensin II substrate. Curr Hypertens Rep. 2014;16(5):429.
   PubMed Web of Science ®Google Scholar
• Urata H, Healy B, Stewart RW, et al. Angiotensin II receptors in normal and failing human hearts. J Clin Endocrinol Metab. 1989;69(1):54–66.
   PubMed Web of Science ®Google Scholar
• Urata H, Healy B, Stewart RW, et al. Angiotensin II-forming pathways in normal and failing human hearts. Circ Res. 1990;66(4):883–890.
   PubMed Web of Science ®Google Scholar
• Urata H, Kinoshita A, Misono KS, et al. Identification of a highly specific chymase as the major angiotensin II-forming enzyme in the human heart. J Biol Chem. 1990;265(36):22348–22357.
   PubMed Web of Science ®Google Scholar
• Balcells E, Meng QC, Hageman GR, et al. Angiotensin II formation in dog heart is mediated by different pathways in vivo and in vitro. Am J Physiol. 1996;271(2 Pt 2):H417–21.
   PubMedGoogle Scholar
• Chandrasekharan UM, Sanker S, Glynias MJ, et al. Angiotensin II-forming activity in a reconstructed ancestral chymase. Science. 1996;271(5248):502–505.
   PubMed Web of Science ®Google Scholar
• Dell’Italia LJ, Meng QC, Balcells E, et al. Compartmentalization of angiotensin II generation in the dog heart. Evidence for independent mechanisms in intravascular and interstitial spaces. J Clin Invest. 1997;100(2):253–258.
   PubMed Web of Science ®Google Scholar
• Zisman LS, Abraham WT, Meixell GE, et al. Angiotensin II formation in the intact human heart. Predominance of the angiotensin-converting enzyme pathway. J Clin Invest. 1995;96(3):1490–1498.
   PubMed Web of Science ®Google Scholar
• Ahmad S, Varagic J, Westwood BM, et al. Uptake and metabolism of the novel peptide angiotensin-(1-12) by neonatal cardiac myocytes. PLoS One. 2011;6(1):e15759.
   PubMed Web of Science ®Google Scholar
• Ahmad S, Wei CC, Tallaj J, et al. Chymase mediates angiotensin-(1-12) metabolism in normal human hearts. J Am Soc Hypertens. 2013;7(2):128–136.
   PubMed Web of Science ®Google Scholar
• Kitamura Y, Oboki K, Ito A. Development of mast cells. Proc Jpn Acad Ser B Phys Biol Sci. 2007;83(6):164–174.
   PubMed Web of Science ®Google Scholar
• Levick SP, Melendez GC, Plante E, et al. Cardiac mast cells: the centrepiece in adverse myocardial remodelling. Cardiovasc Res. 2011;89(1):12–19.
   PubMed Web of Science ®Google Scholar
• Newlands GF, Gibson S, Knox DP, et al. Characterization and mast cell origin of a chymotrypsin-like proteinase isolated from intestines of mice infected with Trichinella spiralis. Immunology. 1987;62(4):629–634.
   PubMed Web of Science ®Google Scholar
• Woodbury RG, Everitt MT, Neurath H. Mast cell proteases. Methods Enzymol. 1981;80(Pt C):588–609.
   PubMedGoogle Scholar
• Metcalfe DD, Baram D, Mekori YA. Mast cells. Physiol Rev. 1997;77(4):1033–1079.
   PubMed Web of Science ®Google Scholar
• Ide H, Itoh H, Tomita M, et al. Cloning of the cDNA encoding a novel rat mast-cell proteinase, rMCP-3, and its expression in comparison with other rat mast-cell proteinases. Biochem J. 1995;311(Pt 2):675–680.
   PubMedGoogle Scholar
• Karlson U, Pejler G, Froman G, et al. Rat mast cell protease 4 is a beta-chymase with unusually stringent substrate recognition profile. J Biol Chem. 2002;277(21):18579–18585.
   PubMed Web of Science ®Google Scholar
• Gallwitz M, Enoksson M, Hellman L. Expression profile of novel members of the rat mast cell protease (rMCP)-2 and (rMCP)-8 families, and functional analyses of mouse mast cell protease (mMCP)-8. Immunogenetics. 2007;59(5):391–405.
   PubMed Web of Science ®Google Scholar
• Guo C, Ju H, Leung D, et al. A novel vascular smooth muscle chymase is upregulated in hypertensive rats. J Clin Invest. 2001;107(6):703–715.
   PubMed Web of Science ®Google Scholar
• Wintroub BU, Schechter NB, Lazarus GS, et al. Angiotensin I conversion by human and rat chymotryptic proteinases. J Invest Dermatol. 1984;83(5):336–339.
   PubMed Web of Science ®Google Scholar
• Yamamoto D, Shiota N, Takai S, et al. Three-dimensional molecular modeling explains why catalytic function for angiotensin-I is different between human and rat chymases. Biochem Biophys Res Commun. 1998;242(1):158–163.
   PubMed Web of Science ®Google Scholar
• Balcells E, Meng QC, Johnson WH Jr., et al. Angiotensin II formation from ACE and chymase in human and animal hearts: methods and species considerations. Am J Physiol. 1997;273(4 Pt 2):H1769–74.
   PubMed Web of Science ®Google Scholar
• Butts B, Goeddel LA, George DJ, et al. Increased inflammation in pericardial fluid persists 48 hours after cardiac surgery. Circulation. 2017;136(23):2284–2286.
   PubMed Web of Science ®Google Scholar
• Urata H. Chymase and matrix metalloproteinase. Hypertens Res. 2007;30(1):3–4.
   PubMed Web of Science ®Google Scholar
• Kirimura K, Takai S, Jin D, et al. Role of chymase-dependent angiotensin II formation in regulating blood pressure in spontaneously hypertensive rats. Hypertens Res. 2005;28(5):457–464.
   PubMed Web of Science ®Google Scholar
• Takai S, Jin D, Chen H, et al. Chymase inhibition improves vascular dysfunction and survival in stroke-prone spontaneously hypertensive rats. J Hypertens. 2014;32(8):1637–1649.
   PubMed Web of Science ®Google Scholar
• Roszkowska-Chojecka MM, Walkowska A, Gawrys O, et al. Effects of chymostatin, a chymase inhibitor, on blood pressure, plasma and tissue angiotensin II, renal haemodynamics and renal excretion in two models of hypertension in the rat. Exp Physiol. 2015;100(9):1093–1105.
   PubMed Web of Science ®Google Scholar
• Urata H, Kinoshita A, Misono KS, et al. Identification of a highly specific chymase as the major angiotensin II-forming enzyme in the human heart. J Biol Chem. 1990;265(36):22348–22357.
   PubMed Web of Science ®Google Scholar
• Lindstedt L, Lee M, Castro GR, et al. Chymase in exocytosed rat mast cell granules effectively proteolyzes apolipoprotein AI-containing lipoproteins, so reducing the cholesterol efflux-inducing ability of serum and aortic intimal fluid. J Clin Invest. 1996;97(10):2174–2182.
   PubMed Web of Science ®Google Scholar
• Jin D, Takai S, Yamada M, et al. Possible roles of cardiac chymase after myocardial infarction in hamster hearts. Jpn J Pharmacol. 2001;86(2):203–214.
   PubMedGoogle Scholar
• Heuston S, Hyland NP. Chymase inhibition as a pharmacological target: a role in inflammatory and functional gastrointestinal disorders? Br J Pharmacol. 2012;167(4):732–740.
   PubMed Web of Science ®Google Scholar
• Takai S, Jin D, Miyazaki M. New approaches to blockade of the renin-angiotensin-aldosterone system: chymase as an important target to prevent organ damage. J Pharmacol Sci. 2010;113(4):301–309.
   PubMed Web of Science ®Google Scholar
• Froogh G, Pinto JT, Le Y, et al. Chymase-dependent production of angiotensin II: an old enzyme in old hearts. Am J Physiol Heart Circ Physiol. 2017;312(2):H223–H31.
   PubMed Web of Science ®Google Scholar
• Kinoshita A, Urata H, Bumpus FM, et al. Multiple determinants for the high substrate specificity of an angiotensin II-forming chymase from the human heart. J Biol Chem. 1991;266(29):19192–19197.
   PubMed Web of Science ®Google Scholar
• Doggrell SA, Wanstall JC. Vascular chymase: pathophysiological role and therapeutic potential of inhibition. Cardiovasc Res. 2004;61(4):653–662.
   PubMed Web of Science ®Google Scholar
• Tamai H, Katoh K, Yamaguchi T, et al. The impact of tranilast on restenosis after coronary angioplasty: the second tranilast restenosis following angioplasty trial (TREAT-2). Am Heart J. 2002;143:506–513.
   PubMed Web of Science ®Google Scholar
• Holmes DR, Savage M, LaBlanche JM, et al. Results of preventionof restenosis with tranilast and its outcomes (PRESTO) trial. Circulation. 2002;106(10):1243–1250.
   PubMed Web of Science ®Google Scholar
• Oyamada S, Bianchi C, Takai S, et al. Chymase inhibition reduces infarction and matrix metalloproteinase-9 activation and attenuates inflammation and fibrosis after acute myocardial ischemia/reperfusion. J Pharmacol Exp Ther. 2011;339(1):143–151.
   PubMed Web of Science ®Google Scholar
• Shiota N, Kakizoe E, Shimoura K, et al. Effect of mast cell chymase inhibitor on the development of scleroderma in tight-skin mice. Br J Pharmacol. 2005;145(4):424–431.
   PubMed Web of Science ®Google Scholar
• Takai S, Jin D, Sakaguchi M, et al. A novel chymase inhibitor, 4-[1-([bis-(4-methyl-phenyl)-methyl]-carbamoyl)3-(2-ethoxy-benzyl)-4-oxo-azetidin e-2-yloxy]-benzoic acid (BCEAB), suppressed cardiac fibrosis in cardiomyopathic hamsters. J Pharmacol Exp Ther. 2003;305(1):17–23.
   PubMed Web of Science ®Google Scholar
• Takai S, Jin D, Sakaguchi M, et al. An orally active chymase inhibitor, BCEAB, suppresses heart chymase activity in the hamster. Jpn J Pharmacol. 2001;86(1):124–126.
   PubMedGoogle Scholar
• Kanefendt F, Thuss U, Becka M, et al. Pharmacokinetics, safety, and tolerability of the novel chymase inhibitor BAY 1142524 in healthy male volunteers. Clin Pharmacol Drug Dev. 2018;00(0):1-13. [Epub ahead of print]
   PubMed Web of Science ®Google Scholar
• Terakawa M, Fujieda Y, Tomimori Y, et al. Oral chymase inhibitor SUN13834 ameliorates skin inflammation as well as pruritus in mouse model for atopic dermatitis. Eur J Pharmacol. 2008;601(1–3):186–191.
   PubMed Web of Science ®Google Scholar
• Ogata A, Fujieda Y, Terakawa M, et al. Pharmacokinetic/pharmacodynamic analyses of chymase inhibitor SUN13834 in NC/Nga mice and prediction of effective dosage for atopic dermatitis patients. Int Immunopharmacol. 2011;11(10):1628–1632.
   PubMed Web of Science ®Google Scholar
• Soga Y, Takai S, Koyama T, et al. Attenuation of adhesion formation after cardiac surgery with a chymase inhibitor in a hamster model. J Thorac Cardiovasc Surg. 2004;127(1):72–78.
   PubMed Web of Science ®Google Scholar
• Doggrell SA, Wanstall JC. Will chymase inhibitors be the next major development for the treatment of cardiovascular disorders? Expert Opin Investig Drugs. 2003;12(8):1429–1432.
   PubMed Web of Science ®Google Scholar
• Hoshino F, Urata H, Inoue Y, et al. Chymase inhibitor improves survival in hamsters with myocardial infarction. J Cardiovasc Pharmacol. 2003;41(Suppl 1):S11–8.
   PubMedGoogle Scholar
• Bot I, Bot M, van Heiningen SH, et al. Mast cell chymase inhibition reduces atherosclerotic plaque progression and improves plaque stability in ApoE-/- mice. Cardiovasc Res. 2011;89(1):244–252.
   PubMed Web of Science ®Google Scholar
• Imada T, Komorita N, Kobayashi F, et al. Therapeutic potential of a specific chymase inhibitor in atopic dermatitis. Jpn J Pharmacol. 2002;90(3):214–217.
   PubMedGoogle Scholar
• Doggrell SA, Wanstall JC. Cardiac chymase: pathophysiological role and therapeutic potential of chymase inhibitors. Can J Physiol Pharmacol. 2005;83(2):123–130.
   PubMed Web of Science ®Google Scholar
• Roszkowska-Chojecka MM, Walkowska A, Gawrys O, et al. Effects of chymostatin, a chymase inhibitor, on blood pressure, plasma and tissue angiotensin II, renal haemodynamics and renal excretion in two models of hypertension in the rat. Exp Physiol. 2015;100(9):1093–1105.
   PubMed Web of Science ®Google Scholar
• Matsumoto T, Wada A, Tsutamoto T, et al. Chymase inhibition prevents cardiac fibrosis and improves diastolic dysfunction in the progression of heart failure. Circulation. 2003;107(20):2555–2558.
   PubMed Web of Science ®Google Scholar
• Takai S, Miyazaki M. Application of a chymase inhibitor, NK3201, for prevention of vascular proliferation. Cardiovasc Drug Rev. 2003;21(3):185–198.
   PubMedGoogle Scholar
• Takai S, Jin D, Nishimoto M, et al. Oral administration of a specific chymase inhibitor, NK3201, inhibits vascular proliferation in grafted vein. Life Sci. 2001;69(15):1725–1732.
   PubMed Web of Science ®Google Scholar
• Guttman-Yassky E, Dhingra N, Leung DY. New era of biologic therapeutics in atopic dermatitis. Expert Opin Biol Ther. 2013;13(4):549–561.
   PubMed Web of Science ®Google Scholar
• Gallwitz M, Hellman L. Rapid lineage-specific diversification of the mast cell chymase locus during mammalian evolution. Immunogenetics. 2006;58(8):641–654.
   PubMed Web of Science ®Google Scholar
• Miyazaki M, Takai S, Jin D, et al. Pathological roles of angiotensin II produced by mast cell chymase and the effects of chymase inhibition in animal models. Pharmacol Ther. 2006;112(3):668–676.
   PubMed Web of Science ®Google Scholar
• Kunori Y, Muroga Y, Iidaka M, et al. Specises differences in angiotensin II generation and degradation by mast cell chymases. J Recept Signal Transduct Res. 2005;25(1):35–44.
   PubMed Web of Science ®Google Scholar
• Eda M, Ashimori A, Akahoshi F, et al. Peptidyl human heart chymase inhibitors. 2. Discovery of highly selective difluoromethylene ketone derivatives with Glu at P3 site. Bioorg Med Chem Lett. 1998;8(8):919–924.
   PubMed Web of Science ®Google Scholar
• Eda M, Ashimori A, Akahoshi F, et al. Peptidyl human heart chymase inhibitors. 1. Synthesis and inhibitory activity of difluoromethylene ketone derivatives bearing P’ binding subsites. Bioorg Med Chem Lett. 1998;8(8):913–918.
   PubMed Web of Science ®Google Scholar
• Hayashi Y, Iijima K, Katada J, et al. Structure-activity relationship studies of chloromethyl ketone derivatives for selective human chymase inhibitors. Bioorg Med Chem Lett. 2000;10(3):199–201.
   PubMed Web of Science ®Google Scholar
• Iijima K, Katada J, Hayashi Y. Symmetrical anhydride-type serine protease inhibitors: structure-activity relationship studies of human chymase inhibitors. Bioorg Med Chem Lett. 1999;9(3):413–418.
   PubMed Web of Science ®Google Scholar
• Taylor SJ, Padyana AK, Abeywardane A, et al. Discovery of potent, selective chymase inhibitors via fragment linking strategies. J Med Chem. 2013;56(11):4465–4481.
   PubMed Web of Science ®Google Scholar
• Greco MN, Hawkins MJ, Powell ET, et al. Discovery of potent, selective, orally active, nonpeptide inhibitors of human mast cell chymase. J Med Chem. 2007;50(8):1727–1730.
   PubMed Web of Science ®Google Scholar
• Janssen Pharmaceutical NV. Inhibitors of chymase. US7872044 (2011).
   Google Scholar
• Aoyama Y. Non-peptidic chymase inhibitors. Expert Opin Ther Pat. 2001;11(9):1423–1428.
   Web of Science ®Google Scholar
• Aoyama Y, Konoike T, Kanda A, et al. Total synthesis of human chymase inhibitor methyllinderone and structure–activity relationships of its derivatives. Bioorg Med Chem Lett. 2001;11(13):1695–1697.
   PubMed Web of Science ®Google Scholar
• Boehringer Ingelheim International GmbH. Quinazolinedione chymase inhibitors. US8377949 (2013).
   Google Scholar
• Boehringer Ingelheim International GmbH. Azaquinazolinedione chymase inhibitors. US8501749 (2013).
   Google Scholar
• Boehringer Ingelheim International GmbH. Chymase inhibitors. US8969348 (2015).
   Google Scholar
• Boehringer Ingelheim International GmbH. Benzimidazolone chymase inhibitors. US9150556 (2015).
   Google Scholar
• Boehringer Ingelheim International GmbH. Aza-benzimidazolone chymase inhibitors. US9062056 (2015).
   Google Scholar
• Bayer Pharma Aktiengesellschaft. Substituted uracils as chymase inhibitors. US9695131 (2017).
   Google Scholar
• Tinel H, Zubov D, Zimmermann K, et al. A novel chymase inhibitor BAY 1142524 reduces fibrosis and improves cardiac function after myocardial infarction in hamster. Circulation. 2017;136(suppl 1):A13624.
   Google Scholar
• Hooshdaran B, Kolpakov MA, Guo X, et al. Dual inhibition of cathepsin G and chymase reduces myocyte death and improves cardiac remodeling after myocardial ischemia reperfusion injury. Basic Res Cardiol. 2017;112(6):62.
   PubMed Web of Science ®Google Scholar
• Ferrario CM, Mullick AE. Renin angiotensin aldosterone inhibition in the treatment of cardiovascular disease. Pharmacol Res. 2017;125(Pt A):57–71.
   PubMedGoogle Scholar
• Reyes S, Varagic J, Ahmad S, et al. Novel cardiac intracrine mechanisms based on Ang-(1–12)/chymase axis require a revision of therapeutic approaches in human heart disease. Curr Hypertens Rep. 2017;19(2):16.
   PubMed Web of Science ®Google Scholar