Characterization of new organic nitrate hybrid drugs covalently bound to valsartan and cilostazol

Pharmacology

Volumn 90, Issue 3-4, 2012, Pages 193-204

  Knorr, Maike ^a,b   Hausding, Michael ^a,b   Schulz, Eberhard ^a   Oelze, Matthias ^a   Rmmler, Robert ^a   Schuff, Alexandra ^a   Daub, Steffen ^a   Schreiner, Jrg ^a   Krller Schn, Swenja ^a   Wenzel, Philip ^a,b   Gori, Tommaso ^a   Burgin, Karl ^c   Sartor, Dirk ^d   Scherhag, Armin ^d   Mnzel, Thomas ^a   Daiber, Andreas ^a  

^a UNIVERSITY MEDICAL CENTER MAINZ   (Germany)

^b Center of Thrombosis and Hemostasis   (Germany)

^c Maxia Strategies LLC   (Switzerland)

^d Cardiolynx AG   (Switzerland)

Author keywords

Hybrid molecules; Nitrate tolerance; Nitric oxide donors; Organic nitrates; Oxidative stress; Platelet aggregation; Vascular function

Indexed keywords

CILOSTAZOL; CLC 1200; CLC 1265; CLC 1280; CLC 2000; CLC 2100; NITRATE; NITRIC OXIDE; ORGANIC COMPOUND; PHOSPHODIESTERASE III; PHOSPHODIESTERASE III INHIBITOR; REACTIVE NITROGEN SPECIES; REACTIVE OXYGEN METABOLITE; UNCLASSIFIED DRUG; VALSARTAN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; COVALENT BOND; DRUG ACTIVITY; DRUG DESIGN; DRUG STRUCTURE; ENZYME INHIBITION; MALE; MITOCHONDRION; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; RAT; TACHYPHYLAXIS; THROMBOCYTE AGGREGATION; THROMBOCYTOPOIESIS; VASOCONSTRICTION; VASODILATATION;

ANIMALS; MALE; NITRATES; OXIDATIVE STRESS; PLATELET AGGREGATION INHIBITORS; RATS; RATS, WISTAR; TETRAZOLES; VALINE; VASOCONSTRICTION; VASODILATOR AGENTS;

EID: 84867223079     PISSN: 00317012     EISSN: 14230313     Source Type: Journal    
DOI: 10.1159/000339861     Document Type: Article

References (27)

1. Abrams J: The role of nitrates in coronary heart disease. Arch Intern Med 1995;155: 357-364.
2. Taylor AL, Ziesche S, Yancy C, Carson P, D'Agostino R Jr, Ferdinand K, Taylor M, Adams K, Sabolinski M, Worcel M, Cohn JN: Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med 2004;351:2049-2057.
3. Kleschyov AL, Oelze M, Daiber A, Huang Y, Mollnau H, Schulz E, Sydow K, Fichtlscherer B, Mulsch A, Munzel T: Does nitric oxide mediate the vasodilator activity of nitroglycerin? Circ Res 2003;93:e104-e112.
4. Katsuki S, Arnold W, Mittal C, Murad F: Stimulation of guanylate cyclase by sodium nitroprusside, nitroglycerin and nitric oxide in various tissue preparations and comparison to the effects of sodium azide and hydroxylamine. J Cyclic Nucleotide Res 1977;3: 23-35.
5. Katsuki S, Arnold WP, Murad F: Effects of sodium nitroprusside, nitroglycerin, and sodium azide on levels of cyclic nucleotides and mechanical activity of various tissues. J Cyclic Nucleotide Res 1977;3:239-247.
6. Fraker TD Jr, Fihn SD, Gibbons RJ, Abrams J, Chatterjee K, Daley J, Deedwania PC, Douglas JS, Ferguson TB Jr, Gardin JM, O'Rourke RA, Williams SV, Smith SC Jr, Jacobs AK, Adams CD, Anderson JL, Buller CE, Creager MA, Ettinger SM, Halperin JL, Hunt SA, Krumholz HM, Kushner FG, Lytle BW, Nishimura R, Page RL, Riegel B, Tarkington LG, Yancy CW: 2007 chronic angina focused update of the ACC/AHA 2002 guidelines for the management of patients with chronic stable angina: a report of the American College of Cardiology/American Heart Association task force on practice guidelines writing group to develop the focused update of the 2002. guidelines for the management of patients with chronic stable angina. Circulation 2007;116:2762-2772.
7. Gori T, Daiber A: Non-hemodynamic effects of organic nitrates and the distinctive characteristics of pentaerithrityl tetranitrate. Am J Cardiovasc Drugs 2009;9:7-15.
8. Munzel T, Daiber A, Gori T: Nitrate therapy: new aspects concerning molecular action and tolerance. Circulation 2011;123: 2132-2144.
9. Martelli A, Rapposelli S, Calderone V: NO-releasing hybrids of cardiovascular drugs. Curr Med Chem 2006;13:609-625.
10. Sakai K, Akima M, Shiraki Y, Hoshino E: Effects of a new antianginal agent, nicorandil, on the cardiovascular system of the miniature pig: with special reference to coronary vasospasm. J Pharmacol Exp Ther 1983;227: 220-228.
11. Imai S, Ushijima T, Nakazawa M, Nabata H, Sakai K: Mechanism of relaxant effects of nicorandil on the dog coronary artery. Arch Int Pharmacodyn Ther 1983;265:274-282.
12. Buccellati C, Sala A, Rossoni G, Capra V, Rovati GE, Di Gennaro A, Folco G, Colli S, Casagrande C: Pharmacological characterization of 2NTX-99 [4-methoxy-n1-(4-trans-nitrooxycyclohexyl)-n3-(3-pyridinylmethyl)-1, 3-benzenedicarboxamide], a potential antiatherothrombotic agent with antithromboxane and nitric oxide donor activity in platelet and vascular preparations. J Pharmacol Exp Ther 2006;317:830-837.
13. Hagos GK, Abdul-Hay SO, Sohn J, Edirisinghe PD, Chandrasena RE, Wang Z, Li Q, Thatcher GR: Anti-inflammatory, antiproliferative, and cytoprotective activity of NO chimera nitrates of use in cancer chemoprevention. Mol Pharmacol 2008;74:1381-1391.
14. Konter J, Mollmann U, Lehmann J: NO donors. Synthesis and antimicrobial activity of novel ketoconazole-NO donor hybrid compounds. Bioorg Med Chem 2008;16: 8294-8300.
15. Fang L, Appenroth D, Decker M, Kiehntopf M, Roegler C, Deufel T, Fleck C, Peng S, Zhang Y, Lehmann J: Synthesis and biological evaluation of NO-donor-tacrine hybrids as hepatoprotective anti-Alzheimer drug candidates. J Med Chem 2008;51:713-716.
16. Gresele P, Momi S: Pharmacologic profile and therapeutic potential of NCX 4016, a nitric oxide-releasing aspirin, for cardiovascular disorders. Cardiovasc Drug Rev 2006;24:148-168.
17. Chowdhury MA, Abdellatif KR, Dong Y, Yu G, Huang Z, Rahman M, Das D, Velazquez CA, Suresh MR, Knaus EE: Celecoxib analogs possessing a N-(4-nitrooxybutyl) piperidin-4-yl or N-(4-nitrooxybutyl)-1,2,3,6- tetrahydropyridin-4-yl nitric oxide donor moiety: synthesis, biological evaluation and nitric oxide release studies. Bioorg Med Chem Lett 2010;20:1324-1329.
18. Lopez GV, Blanco F, Hernandez P, Ferreira A, Piro OE, Batthyany C, Gonzalez M, Rubbo H, Cerecetto H: Second generation of alphatocopherol analogs-nitric oxide donors: synthesis, physicochemical, and biological characterization. Bioorg Med Chem 2007;15: 6262-6272.
19. Munzel T, Sayegh H, Freeman BA, Tarpey MM, Harrison DG: Evidence for enhanced vascular superoxide anion production in nitrate tolerance. A novel mechanism underlying tolerance and cross-tolerance. J Clin Invest 1995;95:187-194.
20. Daiber A, Oelze M, Coldewey M, Bachschmid M, Wenzel P, Sydow K, Wendt M, Kleschyov AL, Stalleicken D, Ullrich V, Mulsch A, Munzel T: Oxidative stress and mitochondrial aldehyde dehydrogenase activity: a comparison of pentaerythritol tetranitrate with other organic nitrates. Mol Pharmacol 2004;66:1372-1382.
21. Koenig A, Roegler C, Lange K, Daiber A, Glusa E, Lehmann J: NO donors. 16. Investigations on structure-activity relationships of organic mononitrates reveal 2-nitrooxyethylammonium nitrate as a high potent vasodilator. Bioorg Med Chem Lett 2007;17: 5881-5885.
22. Geusens P: Naproxcinod, a new cyclooxygenase-inhibiting nitric oxide donator (cinod). Expert Opin Biol Ther 2009;9:649-657.
23. Schuhmacher S, Schulz E, Oelze M, Konig A, Roegler C, Lange K, Sydow L, Kawamoto T, Wenzel P, Munzel T, Lehmann J, Daiber A: A new class of organic nitrates: investigations on bioactivation, tolerance and cross-tolerance phenomena. Br J Pharmacol 2009;158: 510-520.
24. Roegler C, Konig A, Glusa E, Lehmann J: A novel class of nitrovasodilators: potency and in vitro tolerance of organic aminoalkylnitrates. J Cardiovasc Pharmacol 2010;56:484-490.
25. Koenig A, Lange K, Konter J, Daiber A, Stalleicken D, Glusa E, Lehmann J: Potency and in vitro tolerance of organic nitrates: partially denitrated metabolites contribute to the tolerance-devoid activity of pentaerythrityl tetranitrate. J Cardiovasc Pharmacol 2007;50:68-74.
26. Munzel T, Giaid A, Kurz S, Stewart DJ, Harrison DG: Evidence for a role of endothelin 1 and protein kinase C in nitroglycerin tolerance. Proc Natl Acad Sci USA 1995;92:5244-5248.
27. Gambaryan S, Geiger J, Schwarz UR, Butt E, Begonja A, Obergfell A, Walter U: Potent inhibition of human platelets by cGMP analogs independent of cGMP-dependent protein kinase. Blood 2004;103:2593-2600.