Multitarget cardiovascular drugs

Current Medicinal Chemistry

Volumn 18, Issue 17, 2011, Pages 2531-2542

  Trstenjak, U ^a   Kikelj, D ^a  

^a UNIVERSITY OF LJUBLJANA   (Slovenia)

Author keywords

Angiotensin receptor; Angiotensin converting enzyme; Endothelin receptor; Endothelin converting enzyme; Multitarget drugs; Neutral endopeptidase

Indexed keywords

1 (4 DIMETHYLAMINO 3 METHYLBENZYL) 5 DIPHENYLACETYL 4,5,6,7 TETRAHYDRO 1H IMIDAZO[4,5 C]PYRIDINE 6 CARBOXYLIC ACID; 2 (4 BIPHENYLYL) 1 (1H TETRAZOL 5 YL)ETHYLAMINOMETHYLPHOSPHONIC ACID; 2 BUTYL 4 METHYLTHIO 1 [[2' [[[(PROPYLAMINO)CARBONYL]AMINO]SULFONYL][1,1' BIPHENYL] 4 YL]METHYL] 1H IMIDAZOLE 5 CARBOXYLIC ACID; AHU 377; ANGIOTENSIN 1 RECEPTOR ANTAGONIST; ANGIOTENSIN 2 RECEPTOR ANTAGONIST; ANGIOTENSIN RECEPTOR ANTAGONIST; BMS 346567; CARDIOVASCULAR AGENT; CGS 30084; CGS 31447; CGS 34043; CGS 35066; CGS 35601; DAGLUTRIL; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; ENALAPRIL; ENDOTHELIN CONVERTING ENZYME INHIBITOR; ENDOTHELIN RECEPTOR ANTAGONIST; IRBESARTAN; L 159093; L 159689; L 159913; L 163007; L 163958; LBQ 657; LCZ 696; LIGAND; LOSARTAN; NEUTRAL PROTEINASE; OMAPATRILAT; UNCLASSIFIED DRUG;

ANGIONEUROTIC EDEMA; ARTICLE; CARDIOVASCULAR DISEASE; DRUG DESIGN; DRUG MECHANISM; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; DRUG TARGETING; HUMAN; HYPERTENSION; NONHUMAN; STRUCTURE ACTIVITY RELATION;

ANGIOTENSIN RECEPTOR ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; ASPARTIC ACID ENDOPEPTIDASES; CARDIOVASCULAR AGENTS; CARDIOVASCULAR DISEASES; DRUG DESIGN; ENDOTHELINS; ENZYME INHIBITORS; HUMANS; METALLOENDOPEPTIDASES; NATRIURETIC PEPTIDES; NEPRILYSIN; PROTEASE INHIBITORS; RENIN-ANGIOTENSIN SYSTEM;

EID: 79957968155     PISSN: 09298673     EISSN: 1875533X     Source Type: Journal    
DOI: 10.2174/092986711795933768     Document Type: Article

References (58)

1. (a) Morphy, R.; Rankovic, Z. Designed multiple ligands. An emerging drug discovery paradigm. J. Med. Chem., 2005, 48, 6523-6543. (Pubitemid 41504710)
2. (b) Morphy, R.; Rankovic, Z. Designing multiple ligands - Medicinal chemistry strategies and challenges. Curr. Pharm. Design, 2009, 15, 587-600.
3. Huang, S. Rational drug discovery: what can we learn from regulatory networks? Drug Discov. Today, 2002, 7, 163-169.
4. (a) Morphy, R.; Kay, C.; Rankovic, Z. From magic bullets to designed multiple ligands. Drug Discov. Today, 2004, 9, 641-651. (Pubitemid 38981718)
5. (b) Morphy, R.; Rankovic, Z. The physicochemical challenges of designing multiple ligands., J. Med. Chem., 2006, 49, 4961-4970. (Pubitemid 44201054)
6. Bangalore, S.; Kamalakkannan, G.; Parkar, S.; Messerli, F.H. Fixed-dose combinations improve medication compliance: A meta-analysis. Am. J. Med., 2007, 120, 713-719. (Pubitemid 47176510)
7. Eisen, S.A.; Miller, D.K.; Woodward, R.S.; Spitznagel, E.; Przybeck, T.R. The effect of prescribed daily dose frequency on patient medical compliance. Arch. Intern. Med., 1990, 150, 1881-1884. (Pubitemid 20316533)
8. Blonde, L.; Wogen, J.; Kreilick, C.; Seymour, A.A. Greater reductions in A1C in type 2 diabetic patients new to therapy with glyburide/ metformin tablets as compared to glyburide co-administered with metformin. Diabetes Obes. Metab., 2003, 5, 424-431. (Pubitemid 37483604)
9. Glass, G. Cardiovascular combinations. Nat. Rev. Drug Discov., 2004, 3, 731-732. (Pubitemid 39242819)
10. Martelli, A.; Rapposelli, S.; Calderone, V. NO-Releasing hybrids of cardiovascular drugs. Curr. Med. Chem., 2006, 13, 609-625.
11. Martelli, A.; Breschi, M.C.; Calderone, V. Pharmacodynamic hybrids coupling established cardiovascular mechanisms of action with additional nitric oxide releasing properties. Curr. Pharm. Design, 2009, 15, 614-636.
12. Corti, R.; Burnett, Jr. J. C.; Rouleau, J. L.; Ruschitzka, F.; Lüscher, T. F. Vasopeptidase inhibitors: A new therapeutic concept in cardiovascular disease? Circulation, 2001, 104, 1856-1862. (Pubitemid 32963354)
13. Vinson, G.P.; Ho, M.M.; Puddefoot, J.R. The distribution of angiotensin II type 1 receptors, and the tissue renin-angiotensin systems. Mol. Med. Today, 1995, 1, 35-39.
14. Kramkowski, K.; Mogielnicki, A.; Buczko, W. The physiological significance of the alternative pathways of angiotensin II production. J. Physiol. Pharmacol., 2006, 57, 529-539. (Pubitemid 46096103)
15. Kaschina, E.; Unger, T. Angiotensin AT1/AT2 receptors: Regulation, signalling and function. Blood Press., 2003, 12, 70-88. (Pubitemid 36700689)
16. Steckelings, U.M.; Kaschina, E.; Unger, T. The AT2 receptor-a matter of love and hate. Peptides, 2005, 26, 401-409.
17. (a) Imai, T.; Hirata, Y.; Emori, T.; Yanagisawa, M.; Masaki, T.; Marumo, F. Induction of endothelin-1 gene by angiotensin and vasopressin in endothelial cells. Hypertension, 1992, 19, 753-757.
18. (b) Chua, B. H.; Chua, C. C.; Diglio, C. A.; Siu, B. B. Regulation of endothelin-1 mRNA by angiotensin II in rat heartendothelial cells. Biochim. Biophys. Acta, 1993, 1178, 201-206(a). (Pubitemid 23247999)
19. Inguimbert, N.; Poras, H.; Teffo, F.; Beslot, F.; Selkti, M.; Tomas, A.; Scalbert, E.; Bennejean,C.; Renard, P.; Fournié-Zaluski,M. C.; Roques, B. P. N-[2-(Indan-1-yl)-3-mercapto-propionyl] amino acids as highly potent inhibitors of the three vasopeptidases (NEP, ACE, ECE): In vitro and In vivo activities. Bioorg. Med. Chem. Lett., 2002, 12, 2001-2005. (Pubitemid 34756468)
20. Daull, P.; Jeng, A.Y.; Battistini, B. Towards triple vasopeptidase inhibitors for the treatment of cardiovascular diseases. J. Cardiovasc. Pharmacol., 2007, 50, 247-56. (Pubitemid 47428971)
21. Favrat, B.; Burnier, M.; Nussberger, J. Neutral endopeptidase versus angiotensin converting enzyme inhibition in essential hypertension. J. Hypertens., 1995, 13, 797-804.
22. Robl, J.; Sieber-McMaster, E.; Asaad, M. M.; Bird, J. E.; Delaney, N. G.; Barrish, J. C.; Neubeck, R.; Natarajan, S.; Cohen, M.; Rovnyak, G. C.; Huber, G.; Murugesan, N.; Girotra, R.; Cheung, H. S.; Waldron, T.; Petrillo, E. W. Mercaptoacyl dipeptides as dual inhibitors of angiotensin converting enzyme and neutral peptidase. Preliminary structure-activity studies. Bioorg. Med. Chem. Lett., 1994, 4, 1783-1789.
23. Robl, J. A.; Sun, C.-Q.; Stevenson, J.; Ryono, D. E.; Simpkins, L. M.; Cimarusti, M. P.; Dejneka, T.; Slusarchuk, W. A.; Chao, S.; Stratton, L.; Misra, R. N.; Bednarz, M. S.; Asaad, M. M.; Cheung, H. S.; Abboa-Offei, B. E.; Smith, P. L.; Mathers, P. D.; Fox, M.; Schaeffer, T. R.; Seymour, A. A.; Trippodo, N. C. Dual metalloprotease inhibitors: mercaptoacetyl-based fused heterocyclic dipeptide mimetics as inhibitors of angiotensin-converting enzyme and neutral endopeptidase. J. Med. Chem., 1997, 40, 1570-1577. (Pubitemid 27231460)
24. Flynn, G. A.; Beight, D. W.; Mehdi, S.; Koehl, J. R.; Giroux, E. L.; French, J. F.; Hake, P. W.; Dage, R. C. Application of conformationally restricted Phe-Leu dipeptide mimetic to the design of a combined inhibitor of angiotensin I converting enzyme and neutral endopeptidase 24.11. J. Med. Chem., 1993, 36, 2420-2430.
25. Zhang, X.; Recchia, F.A.; Bernstein, R. Kinin-mediated coronary nitric oxide production contributes to the therapeutic action of angiotensin converting enzyme and neutral endopeptidase inhibitors and amlodipine in the treatment in heart failure. J. Pharmacol. Exp. Ther., 1999, 288, 742-751. (Pubitemid 29119690)
26. Messerli, F.H.; Nussberger, J. Vasopeptidase inhibition and angio-oedema. Lancet, 2000, 356, 608-609. (Pubitemid 30627581)
27. Greaves, M.; Lawlor, F. Angioedema: manifestations and management. J. Am. Acad. Dermatol., 1991, 25, 155-161.
28. Kaplan, A.P.; Greaves, M.W. Angioedema. J. Am. Acad. Dermatol., 2005, 53, 373-388. (Pubitemid 41195957)
29. Coats, A. J. S. Omapatrilat- the story of Overture and Octave. Int. J. Cardiol., 2002, 86, 1-4. (Pubitemid 35251888)
30. Sulpizio, A.C; Pullen, M.A.; Edwards, R.M.; Louttit, J.B.; West, R.; Brooks, D.P. Mechanism of vasopeptidase inhibitor-induced plasma extravasation: comparison of omapatrilat and the novel neutral endopeptidase 24.11/angiotensin-converting enzyme inhibitor GW796406. J. Pharmacol. Exp. Ther., 2005, 315, 1306-1313. (Pubitemid 41635419)
31. Fryer, R.M.; Segreti, J.; Banfor, P.N.; Widomski, D.L.; Backes, B.J.; Lin, C.W.; Ballaron, S.J.; Cox, B.F.; Trevillyan, J.M.; Reinhart, G.A.; von Geldern, T.W. Effect of bradykinin metabolism inhibitors on evoked hypotension in rats: rank efficacy of enzymes associated with bradykininmediated angioedema. Br. J. Pharmacol., 2008, 153, 947-955. (Pubitemid 351328937)
32. Kentsch, M.; Otter, W.; Drummer, C.; et al. Neutral endopeptidase 24.11 inhibition may not exhibit beneficial haemodynamic effects in patients with congestive heart failure. Eur. J. Clin. Pharmacol., 1996, 51, 269-272. (Pubitemid 26422972)
33. Delombaert, S.; Blanchard, L.; Stamford, L. B.; Tan, J.; Wallace, E. M.; Satoh, Y.; Fitt, J.; Hoyer, D.; Simonsbergen, D.; Moliterni, J.; Marcopoulos, N.; Savage, P.; Chou, M.; Trapani, A.J.; Arco, Y.J. Potent and selective nonpeptidic inhibitors of endothelin-converting enzyme-1 with sustained duration of action. J. Med. Chem., 2000, 43, 488-504. (Pubitemid 30102089)
34. Delombaert, S.; Ghai, R. D.; Jeng, A. Y.; Trapani, A. J.; Webb, R. L. Pharmacological Profile of a Non-peptidic Dual Inhibitor of Neutral Endopeptidase 24.11 and Endothelin-Converting Enzyme. Biochem. Biophys. Res. Commun., 1994, 204, 407-412.
35. Delombaert, S.; Stamford, L. B.; Blanchard, L.; Tan, J.; Hoyer, D.; Diefenbacher, C. G.; Wei, D.; Wallace, E. M.; Moskal, M. A.; Savage, P.; Arco, Y.J. Potent non-peptidic dual inhibitors of endothelin-converting enzyme and neutral endopeptidase 24.11. Bioorg. Med. Chem. Lett., 1997, 7, 1059-1064. (Pubitemid 27193367)
36. Dickstein, K.; de Voogd, H. J.; Miric, M. P.; Willenbrock, R.; Mitrovic, V.; Pacher, R.; Koopman, P. A. Effect of single doses of SLV306, an inhibitor of both neutral endopeptidase and endothelin-converting enzyme, on pulmonary pressures in congestive heart failure. Am. J. Cardiol., 2004, 94, 237-239. (Pubitemid 38902881)
37. Fink, C.A.; Moskal, M.; Firooznia, F.; Hoyer, D.; Symonsbergen, D.; Wei, D.; Qiao, Y.; Savage, P.; Beil, M.E.; Trapani, A.J.; Jeng, A.Y. Design and synthesis of potent thiol-based inhibitors of endothelin converting enzyme-1. Bioorg. Med.Chem. Lett., 2000, 10, 2037-1039.
38. Firooznia, F.; Gude, C.; Chan, K.; Tan, J.; Fink, C.A.; Savage, P.; Beil, M.E.; Bruseo, C.W.; Trapani, A.J.; Jeng, A.Y. Synthesis and biological activity of potent heterocyclic thiol- based inhibitors of endothelin-converting enzyme- 1. Bioorg. Med.Chem. Lett., 2002, 12, 3059-3062.
39. Battistini, B.; Daull, P.; Jeng, A.J. CGS 35601, a triple inhibitor of angiotensin converting enzyme, neutral endopeptidase and endothelin converting enzyme. Cardiovasc. Drug Rev., 2005, 23, 317-330. (Pubitemid 43853854)
40. Inguimbert, N.; Coric, P.; Poras, H.; Meudal, H.; Teffot, F.; Fournie-Zaluski, M.C.; Roques, B.P. Toward an optimal joint recognition of the S1' subsite of endothelin converting enzyme-1 (ECE-1), angiotensin converting enzyme (ACE), and neutral endopeptidase (NEP). J. Med. Chem., 2002, 45, 1477-1486. (Pubitemid 34246111)
41. Inguimbert, N.; Poras, H.; Teffot, F.; Beslot, F.; Selkti, M.; Tomas, A.; Scalbert, E.; Bennejean, C.; Renard, P.; Fournie-Zaluski, M.C.; Roques, B.P. N-[2-(indan-1-yl)-3-mercapto-propionyl] amino acids as highly potent inhibitors of the three vasopeptidases (NEP, ACE, ECE): in vitro and in vivo activities. Bioorg. Med.Chem. Lett., 2002, 12, 2001-2005. (Pubitemid 34756468)
42. Daull, P.; Lepage, R.; Benrezzak, O.; Cayer, J.; Beaudoin, M.; Belleville, K.; Blouin, A.; Sirois, P.; Nantel, F.; Jeng, A.Y.; Battistini, B. The first preclinical pharmacotoxicological safety assessment of CGS 35601, a triple vasopeptidase inhibitor, in chronically instrumented, conscious, and unrestrained spontaneously hypertensive rats. Drug Chem. Toxicol., 2006, 29, 183-202.
43. Massart, P. E.; Hodeige, D. G.; Van Mechelen, H.; Charlier, A.A.; Ketelslegers, J. M.; Heyndrickx, G. R.; Donckier, J. E. Angiotensin II and endothelin-1 receptor antagonists have cumulative hypotensive effects in canine Page hypertension. J. Hypertens., 1998, 16, 835-841. (Pubitemid 28247967)
44. Bohlender, J.; Gerbaulet, S.; Kramer, J.; Gross, M.; Kirchengast, M.; Dietz, R. Synergistic effects of AT1 and ETA receptor blockade in a transgenic, angiotensin II-dependent, rat model. Hypertension, 2000, 35, 992-997. (Pubitemid 30303963)
45. Walsh, T.; Fitch, K.; Williams, D.; Murphy, K.; Nolan, N.; Pettibone, D.; Chang, R.; O'Malley, S.; Clineschmidt, B.; Veber, D.; Greenlee, W. Potent dual antagonists of endothelin and angiotensin II receptors derived from Rphenoxyphenylacetic acids (Part III). Bioorg. Med. Chem. Lett., 1995, 5, 1155-1158.
46. Murugesan, N.; Tellew, J.; Gu, Z.; Kunst, B.; Fadnis, L.; Cornelius, L.; Baska, R.; Yang, Y.; Beyer, S.; Monshizadegan, H.; Dickinson, K.; Panchal, B.; Valentine, M.; Chong, S.; Morrison, R.; Carlson, K.; Powell, J.; Moreland, S.; Barrish, J.; Kowala, M.; Macor, J. Discovery of N-isoxazolyl biphenylsulfonamides as potent dual angiotensin II and endothelin A receptor antagonists. J. Med. Chem., 2002, 45, 3829-3835. (Pubitemid 35024288)
47. Murugesan, N.; Gu, Z.; Fadnis, L.; Tellew, J.; Baska, R.; Yang, Y.; Beyer, S.; Monshizadegan, H.; Dickinson, K.; Valentine, M.; Humphreys, W.; Lan, S.; Ewing, W.; Carlson, K.; Kowala, M.; Zahler, R.; Macor, J. Dual angiotensin II and endothelin A receptor antagonists: Synthesis of 2'- substituted N-3-isoxazolyl biphenylsulfonamides with improved potency and pharmacokinetics. J. Med. Chem., 2005, 48, 171-179. (Pubitemid 40105258)
48. Timmermans, P. B.; Wong, P. C.; Chiu, A. T. Angiotensin II receptors and angiotensin II receptor antagonists. Pharmacol. Rev., 1993, 45, 205-251. (Pubitemid 23191415)
49. Dinh, D.T.; Frauman A.G.; Johnston, C.I.; Fabiani M.E. Angiotensin receptors: distribution, signalling and function. Clin. Sci., 2001, 100, 481-492. (Pubitemid 32434113)
50. Laszlo, S.; Quagliato, C.; Greenlee, W.; Patchett, A.; Chang, R.; Lotti, V.; Chen, T.; Scheck, S.; Faust, K. A. potent, orally active, balanced affinity angiotensin II AT1 antagonist and AT2 binding inhibitor. J. Med. Chem. 1993, 36, 3207-3210. (Pubitemid 23326278)
51. Chang, L. L.; Ashton, W. T.; Flanagan, K.L.; Chen, T.-B.; O'Malley, S. S.; Zingaro, G. J.; Siegl, P. K. S.; Kivlighn, S. D.; Lotti, V. J.; Chang, R. S. L.; Greenlee, W. J.Triazolinone biphenylsulfonamides as angiotensin II receptor antagonists with high affinity for both the AT1 and AT2 subtypes. J. Med. Chem., 1994, 37, 4464-4478.
52. Chang, L.L; Ashton, W.T.; Flanagan, K.F.; Chen, T.B.; O'Malley, S.S.; Zingaro, G.J.; Kivlighn, S.D.; Siegl, P.K.S.; Lotti, V.J.; Chang, R.S.L.; Greenlee, W.J. Potent and orally active angiotensin II receptor antagonists with equal affinity for human AT1 and AT2 subtypes1. J. Med. Chem., 1995, 38, 3741-3758.
53. Deprez, P.; Guillaume, J.; Becker, R.; Corbier, A.; Didierlaurent, S.; Fortin, M.; Frechet, D.; Hamon, G.; Heckmann, B.; Heitsch, H.; Kleemann, H.W.; Vevert, J.P.; Vincent, J.C.; Wagner, A.; Zhang, J. Sulfonylureas and sulfonylcarbamates as new non-tetrazole angiotensin II receptor antagonists. Discovery of a highly potent orally active (imidazolylbiphenylyl)sulfonylurea (HR 720). J. Med. Chem., 1995, 38, 2357-2377.
54. Deprez, P.; Guillaume, J.; Corbier, A.; Fortin, M.; Vevert, J.P.; Heckmann, B. Balanced AT1 and AT2 angiotensin II antagonists. II. Potent 5 - hydroxyacid imidazolyl biphenyl sulfonylureas. Bioorg. Med. Chem. Lett., 1995, 5, 2611-2616.
55. Mistry, N.B.; Westheim, A.S.; Kjeldsen, S.E. The angiotensin receptor antagonist valsartan: a review of the literature with a focus on clinical trials. Expert Opin. Pharmacother., 2006, 7, 575-581.
56. Ksander, G.M.; Ghai, R.D.; deJesus, R.; Diefenbacher, C.G.; Yuan, A.; Berry, C.; Sakane, Y.; Trapani A. Dicarboxylic acid dipeptide neutral endopeptidase inhibitors. J. Med. Chem., 1995, 38, 1689-1700.
57. Gu, J.; Noe, A.; Chandra, P.; Al-Fayoumi, S.; Ligueros-Saylan, M.; Sarangapani, R.; Maahs, S.; Ksander, G.; Rigel, D.F.; Jeng, A.Y.; Lin, T.H.; Zheng, W.; Dole, W.P. Pharmacokinetics and pharmacodynamics of LCZ696, a novel dual-acting angiotensin receptor-neprilysin inhibitor (ARNi). J. Clin. Pharmacol., 2010, 50, 401-414.
58. Ruilope, L.M.; Dukat, A.; Böhm, M.; Lacourciere, Y.; Gong, J.; Lefkowitz, M.P. Blood-pressure reduction with LCZ696, a novel dual-acting inhibitor of the angiotensin II receptor and neprilysin: a randomised, double blind, placebo-controlled, active comparator study. Lancet, 2010, 375, 1255-1266.