(Nitrooxyacyloxy)methyl esters of aspirin as novel nitric oxide releasing aspirins

Journal of Medicinal Chemistry

Volumn 52, Issue 16, 2009, Pages 5058-5068

  Lazzarato, Loretta ^a   Donnola, Monica ^a   Rolando, Barbara ^a   Chegaev, Konstantin ^a   Marini, Elisabetta ^a   Cena, Clara ^a   Di Stilo, Antonella ^a   Fruttero, Roberta ^a   Biondi, Stefano ^b   Ongini, Ennio ^b   Gasco, Alberto ^a  

^a UNIVERSITY OF TURIN   (Italy)

^b Nicox Research Institute   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

(NITROOXYACYLOXY)METHYL ESTER DERIVATIVE; 1 [[4 [[3 (NITROOXY)PROPYL]THIO]BENZOYL]OXY]ETHYL 2 (ACETYLOXY)BENZOATE; 1 CHLOROETHYL 2 (ACETYLOXY)BENZOATE; 2 [3 (NITROOXY)PROPOXY]BENZOIC ACID; 3 (2 FORMYLPHENOXY)PROPYLNITRATE; 3 (3 FORMYLPHENOXY)PROPYLNITRATE; 3 (4 FORMYLPHENOXY)PROPYLNITRATE; 3 (4 FORMYLPHENYL)PROPYLNITRATE; 3 [3 (NITROOXY)PROPOXY]BENZOIC ACID; [[2 (ACETYLOXY)BENZOYL]OXY]METHYL 6 (HYDROXYMETHYL)PYRIDINE 2 CARBOXYLATE; [[2 (ACETYLOXY)BENZOYL]OXY]METHYL 6 [(NITROOXY)METHYL]PYRIDINE 2 CARBOXYLATE; [[2 [3 (NITROOXY)PROPOXY]BENZOYL]OXY]METHYL 2 (ACETYLOXY)BENZOATE; [[2 [3 (NITROOXY)PROPOXY]BENZOYL]OXY]METHYL 2 (HYDROXYBENZOATE); [[3 [3 (NITROOXY)PROPOXY]BENZOYL]OXY]METHYL 2 (ACETYLOXY)BENZOATE; [[4 [2,3 BIS(NITROOXY)PROPOXY]BENZOYL]OXY]METHYL 2 (ACETYLOXY)BENZOATE; [[4 [2,3 BIS(NITROOXY)PROPYL]BENZOYL]OXY]METHYL 2 (ACETYLOXY)BENZOATE; [[4 [3 (NITROOXY)PROPOXY]BENZOYL]OXY]METHYL 2 (ACETYLOXY)BENZOATE; [[4 [3 (NITROOXY)PROPYL]BENZOYL]OXY]METHYL 2 (ACETYLOXY)BENZOATE; [[4 [[2,3 BIS(NITROOXY)PROPYL]THIO]BENZOYL]OXY]METHYL 2 (ACETYLOXY)BENZOATE; [[4 [[3 (NITROOXY)PROPYL]SULFINYL]BENZOYL]OXY]METHYL 2 (ACETYLOXY)BENZOATE; [[4 [[3 (NITROOXY)PROPYL]SULFONYL]BENZOYL]OXY]METHYL 2 (ACETYLOXY)BENZOATE; [[4 [[3 (NITROOXY)PROPYL]THIO]BENZOYL]OXY]METHYL 2 (ACETYLOXY)BENZOATE; [[5,6 BIS(NITROOXY)HEXANOYL]OXY]METHYL 2 (ACETYLOXY)BENZOATE; [[6 (NITROOXY)HEXANOYL]OXY]METHYL 2 (ACETYLOXY)BENZOATE; [[6,7 BIS(NITROOXY)HEPTANOYL]OXY]METHYL 2 (ACETYLOXY)BENZOATE; [[7 (NITROOXY)HEPTANOYL]OXY]METHYL 2 (ACETYLOXY)BENZOATE; ACETYLSALICYLIC ACID DERIVATIVE; GUANYLATE CYCLASE; NITRIC OXIDE DONOR; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANIMAL TISSUE; AORTA STRIP; AREA UNDER THE CURVE; ARTERY DILATATION; ARTICLE; CONTROLLED STUDY; DRUG HYDROLYSIS; DRUG MECHANISM; DRUG POTENCY; DRUG RELEASE; DRUG SCREENING; DRUG STABILITY; DRUG SYNTHESIS; ENZYME ACTIVATION; HUMAN; MALE; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION; THROMBOCYTE AGGREGATION INHIBITION; VASODILATATION;

ANIMALS; AORTA; ASPIRIN; DRUG STABILITY; ESTERS; HUMANS; HYDROGEN-ION CONCENTRATION; HYDROLYSIS; MALE; MUSCLE CONTRACTION; MUSCLE, SMOOTH, VASCULAR; NITRATES; NITRIC OXIDE DONORS; PLATELET AGGREGATION INHIBITORS; RATS; RATS, WISTAR; STRUCTURE-ACTIVITY RELATIONSHIP; VASODILATOR AGENTS;

EID: 69049098127     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm900587h     Document Type: Article

References (39)

1. Singh, G.; Triadafilopoulos, G. Epidemiology of NSAID induced gastrointestinal complications. J. Rheumatol. 1999, 26 (Suppl. 56), 18-24.
2. Morgan, G. The established and emerging uses of aspirin. Basic Clin. Pharmacol. 2006, 99, 283-286.
3. Patrono, C.; Rocca, B. Aspirin: promise and resistance in the new millennium. Arterioscler. Thromb. Vasc. Biol. 2008, 28, S25-S32.
4. Yasuda, O.; Takemura, Y.; Kawamoto, H.; Rakugi, H. Aspirin: recent developments. Cell. Mol. Life Sci. 2008, 65, 354-358.
5. Arber, N.; Levin, B. Chemoprevention of colorectal cancer: ready for routine use? Curr. Top. Med. Chem. 2005, 5, 517-525.
6. Schoen, R. T.; Vender, R. J. Mechanisms of nonsteroidal antiinflammatory drug-induced gastric damage. Am. J. Med. 1989, 86, 449-458.
7. Wolfe, M. M.; Lichtenstein, D. R.; Singh, G. Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs. New Engl. J. Med. 1999, 340, 1888-1899.
8. Rainsford, K. D.; Whitehouse, M. W. Gastric irritancy of aspirin and its congeners: anti-inflammatory activity without this sideeffect. J. Pharm. Pharmacol. 1976, 28, 599-601.
9. Nielsen, N. M.; Bundgaard, H. Evaluation of glycolamide esters and various other esters of aspirin as true aspirin prodrugs. J. Med. Chem. 1989, 32, 727-734 and references therein.
10. Wallace, J. L.; Granger, D. N. The cellular and molecular basis of gastric mucosal defence. FASEB J. 1996, 10, 731-740.
11. Lefer, A. M.; Lefer, D. J. Therapeutic role of nitric oxide donors in the treatment of cardiovascular desease. Drugs Future 1994, 19, 665-672.
12. Kerwin, J. F. Jr.; Lancaster, J. R.; Feldman, P. L. Nitric oxide: a new paradigm for second messengers. J. Med. Chem. 1995, 38, 4343-4362.
13. Miller, M. R.; Megson, I. L. Recent developments in nitric oxide donor drugs. Br. J. Pharmacol. 2007, 151, 305-321.
14. Wallace, J. L. Building a better aspirin: gaseous solutions to a century-old problem. Br. J. Pharmacol. 2007, 152, 421-428 and references therein.
15. Wang, P. G.; Xian, M.; Tang, X.; Wu, X.; Wen, Z.; Cai, T.; Janczuk, A. J. Nitric oxide donors: chemical activities and biological applications. Chem. Rev. 2002, 102, 1091-1134.
16. Gilmer, J. F.; Moriarty, L. M.; Clancy, J. M. Evaluation of nitratesubstituted pseudocholine esters of aspirin as potential nitroaspirin. Bioorg. Med. Chem. Lett. 2007, 17, 3217-3220.
17. Cena, C.; Lolli, M. L.; Lazzarato, L.; Guaita, E.; Morini, G.; Coruzzi, G.; McElroy, S. P.; Megson, I. L.; Fruttero, R.; Gasco, A. Antiinflammatory, gastrosparing, and antiplatelet properties of new NO-donor esters of aspirin. J. Med. Chem. 2003, 46, 747-754.
18. Velázquez, C.; Rao, P. N. P.; Knaus, E. E. Novel nonsteroidal antiinflammatory drugs possessing a nitric oxide donor diazen-1-ium-1,2-diolate moiety: design, synthesis, biological evaluation, and nitric oxide release studies. J. Med. Chem. 2005, 48, 4061-4067.
19. 2-Acetoxymethyl-protected diazeniumdialate-based NSAIDs (NONO-NSAIDs): synthesis, nitric oxide release, and biological evaluation studies. Bioorg. Med. Chem. 2007, 15, 4767-4774.
20. Velázquez, C. A.; Chen, Q.-H.; Citro, M. L.; Keefer, L. K.; Knaus, E. E. Second-generation aspirin and indomethacin prodrugs possessing an O-(acetoxymethyl)-1-(2-carboxypyrrolidin-1-yl)diazenium-1,2-diolate nitric oxide donor moiety: design, synthesis, biological evaluation, and nitric oxide release studies. J. Med. Chem. 2008, 51, 1954-1961.
21. Carini, M.; Aldini, G.; Orioli, M.; Maffei Facino, R. In vitro metabolism of a nitroderivative of acetylsalicylic acid (NCX4016) by rat liver: LC and LC-MS studies. J. Pharm. Biomed. 2002, 29, 1061-1071.
22. Gao, J.; Kashfi, K.; Rigas, B. In vitro metabolism of nitric oxide-donating aspirin: the effect of positional isomerism. J. Pharmacol. Exp. Ther. 2005, 312, 989-997.
23. Rao, C. V.; Joseph, S.; Gao, L.; Patrolla, J. M. R.; Choi, C. I.; Kopelovich, L.; Steele, V. E.; Rigas, B. Pharmacokinetic and pharmacodynamic study of NO-donating aspirin in F344 rats. Int. J. Oncol. 2008, 33, 799-805.
24. Agersborg, H. P. K.; Batchelor, A.; Cambridge,G. W.; Rule, A. W. The pharmacology of penamecillin. Br. J. Pharmacol. 1966, 26, 649-655.
25. Garvey, D. S.; Letts, G.; Earl, R. A.; Ezawa, M.; Fang, X.; Gaston, R. D.; Khanapure, S. P.; Lin, C.-E.; Ranatunge, R. R.; Stevenson, C. A.; Wey, J.-J. Nitric oxide enhancing diuretic compounds, compositions and methods of use. Patent Application Publication US2006/0189603, August 24, 2006.
26. Lazzarato, L.; Rolando, B.; Lolli, M. L.; Tron, G. C.; Fruttero, R.; Gasco, A.; Deleide, G.; Guenther, H. L. Synthesis of NO-donor bisphosphonates and their in vitro action on bone resorption. J. Med. Chem. 2005, 48, 1322-1329.
27. Song, H.; Li, J.; Wang, Y.; Zhang, S.; Liu, Y.; Ren, Z. Synthesis and anti-inflammatory/analgesia activities of pyrrolizinones. Zhongguo Yaowu Huaxe Zazhi 2005, 15, 266-270.
28. Lazzarato, L.; Donnola, M.; Rolando, B.; Marini, E.; Cena, C.; Coruzzi, G.; Guaita, E.; Morini, G.; Fruttero, R.; Gasco, A.; Biondi, S.; Ongini, E. Searching for new NO-donor aspirin-like molecules: a new class of nitrooxy-acyl derivatives of salicylic acid. J. Med. Chem. 2008, 51, 1894-1903.
29. Chegaev, K.; Lazzarato, L.; Rolando, B.; Marini, E.; Tosco, P.; Cena, C.; Fruttero, R.; Bertolini, F.; Reist, M.; Carrupt, P.-A.; Lucini, V.; Fraschini, F.; Gasco, A. NO-donor melatonin derivatives: synthesis and in vitro pharmacological characterization. J. Pineal Res. 2007, 42, 371-385.
30. Breschi, M. C.; Calderone, V.; Digiacomo, M.; Macchia, M.; Martelli, A.; Martinotti, E.; Minutolo, F.; Rapposelli, S.; Rossello, A.; Testai, L.; Balsamo, A. New NO-releasing pharmacodynamic hybrids of Losartan and its active metabolite: design, synthesis, and biopharmacological properties. J. Med. Chem. 2006, 49, 2628-2639.
31. Buchwald, P. Structure-metabolism relationships: steric effects and the enzymatic hydrolysis of carboxylic esters. Mini Rev. Med. Chem. 2001, 1, 101-111.
32. Weber, A. A.; Neuhaus, T.; Seul, C.; Dusing, R.; Schror, K.; Sachinidis, A.; Vetter, H. Biotransformation of glyceryl trinitrate by blood platelets as compared to vascular smooth muscle cells. Eur. J. Pharmacol. 1996, 309, 209-213.
33. Poradosu, E.; Gazit, A.; Reuveni, H.; Levitzki, A. α-Cyanocinnamide derivatives: a new family of non-peptide, non-sulphydryl innhibitors of Ras farnesilation. Bioorg. Med. Chem. 1999, 7, 1727-1736.
34. Cai, Z.; Feng, J.; Guo, Y.; Li, P.; Shen, Z.; Chu, F.; Guo, Z. Synthesis and evaluation of azaindole-r-alkyloxyphenilpropionic acid analogues asPPARr/γ agonists. Bioorg. Med. Chem. 2006, 14, 866-874.
35. Bancroft, S. F.; Thompson, M. J.; Frimpong, N.; Mullins, R. J.; Pugh, C. Synthesis and thermotropic behavior of polynorbornenes with laterally attached 2,5-bis[(4′-n-alkylthiobenzoyl)oxy]benzyl mesogens. Polym. Prepr. 2007, 48, 1001-1002.
36. Wrobel, J.; Green, D.; Jetter, J.; Kao, W.; Rogers, J.; Claudia Perez, M.; Hardenburg, J.; Deecher, D. C.; Lopez, F. J.; Arey, B. J.; Shen, E. S. Synthesis of (bis)sulfonic acid, (bis)benzamides as follicle-stimulating hormone (FSH) antagonists. Bioorg. Med. Chem. 2002, 10, 639-656.
37. Fechtig, B. 7-Beta-acylamido-3-cephem-4-carboxylic-acid esters, process for their preparation, pharmaceutical compositions and their application. European patent EP0136266, September 17, 1984.
38. Pellegata, R.; Italia, A.; Villa, M.; Palmisano, G.; Lesma, G. A facile preparation of primary carboxamides. Synthesis 1985, 517-519.
39. Green, T. W., Wuts, P. G. M. Protection for the carbonyl group. In Protective Groups in Organic Synthesis, 3rd ed.; John Wiley & Sons: New York, 1999; pp 293-368.