Design and synthesis of novel pyridoxine 5′-phosphonates as potential antiischemic agents

Journal of Medicinal Chemistry

Volumn 46, Issue 17, 2003, Pages 3680-3687

  Pham, Vinh ^a   Zhang, Wenlian ^a   Chen, Vince ^a   Whitney, Tara ^a   Yao, John ^a   Froese, Doug ^a   Friesen, Albert D ^a   Diakur, James M ^a   Haque, Wasim ^a  

^a Medicure International Inc   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

[(3,7 DIHYDROXY 6 METHYL 1,3 DIHYDROFURO[3,4 C]PYRIDIN 3 YL)DIFLUOROMETHYL]PHOSPHONIC ACID; [FLUORO (5 HYDROXY 4 HYDROXYMETHYL 6 METHYLPYRIDIN 3 YL)METHYL]PHOSPHONIC ACID; DICHLOROACETIC ACID; NATURAL PRODUCT; PHOSPHONIC ACID DERIVATIVE; PYRIDOXAL 5 PHOSPHATE; PYRIDOXINE 5' PHOSPHONATE DERIVATIVE; SODIUM CHLORIDE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BOLUS INJECTION; CONTROLLED STUDY; CORONARY ARTERY BLOOD FLOW; DISEASE MODEL; DOSE RESPONSE; DRUG DEGRADATION; DRUG DESIGN; DRUG EFFICACY; DRUG ELIMINATION; DRUG MECHANISM; DRUG SENSITIVITY; DRUG STABILITY; DRUG STRUCTURE; DRUG SYNTHESIS; FATTY ACID OXIDATION; GLUCOSE OXIDATION; HEART INFARCTION SIZE; HEART MUSCLE ISCHEMIA; HEART MUSCLE REPERFUSION; HEART PROTECTION; HEART WORK; MALE; NONHUMAN; PHOTOSENSITIVITY; RAT; REPERFUSION INJURY; STRUCTURE ACTIVITY RELATION;

ACUTE TOXICITY TESTS; ANIMALS; CARDIOVASCULAR AGENTS; CORONARY STENOSIS; DRUG STABILITY; FATTY ACIDS; GLUCOSE; GLYCOLYSIS; LETHAL DOSE 50; LIGHT; MOLECULAR MIMICRY; MYOCARDIAL INFARCTION; MYOCARDIAL REPERFUSION INJURY; MYOCARDIUM; OXIDATION-REDUCTION; PHOSPHONIC ACIDS; PYRIDOXAL PHOSPHATE; RATS; RATS, SPRAGUE-DAWLEY; RATS, WISTAR; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0043234174     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm0300678     Document Type: Article

References (28)

1. Rineheart, J. F.; Greenberg, L. D. Arteriosclerotic lesions in pyridoxine-deficient monkeys. Am. J. Pathol. 1949, 25, 481-491.
2. Wang, X.; Dakshinamurti, K.; Musat, S.; Dhalla, N. S. Pyridoxal 5-phosphate is an ATP-receptor antagonist in freshly isolated rat cardiomyocytes. J. Mol. Cell Cardiol. 1999, 31, 1063-1072.
3. Serfontein, W. J.; Ubbink, J. B.; De Villiers, L. S.; Rapley, C. H.; Becker, P. J. Plasma pyridoxal-5-phosphate level as risk index for coronary artery disease. Atherosclerosis 1985, 55, 357-361.
4. Ellis, J. M.; McCully, K. S. Prevention of myocardial infarction by vitamin B6. Res. Commun. Pathol. Pharmacol. 1995, 89, 208-220.
5. Abdelmouttaleb, I.; Danchin, N.; Aimone-Gastin, I.; Namour, F.; Angioi, M.; Gelot, M.-A.; Bennani, N.; Lambert, D.; Jeandel, C.; Guéany. Homocysteine, vitamins B6, B12, folate, and risk of coronary artery disease in patients undergoing diagnostic coronary angiography. Amino Acids 2000, 18, 139-146.
6. Robinson, K.; Mayer, E. L.; Miller, D. P.; Green, R.; van Lente, F.; Gupta, A.; Kottke-Marchant, K.; Savon, S. R.; Selub, J.; Nissen, S. E.; Kutner, M.; Topol, E. J.; Jacobsen, D. W. Hyperhomocysteinemia and low pyridoxal phosphate. Circulation 1995, 92, 2825-2830.
7. Robinson, K.; Arheart, K.; Refsum, H.; Brattström, L.; Boers, G.; Ueland, P.; Rubba, P.; Palma-Reis, R.; Meleady, R.; Daly, L.; Witteman, J.; Graham, I. Low circulating folate and vitamin B6 concentrations risk factors for stroke, peripheral vascular disease, and coronary disease. Circulation 1998, 97, 437-443.
8. Miner, S. E. S.; Cole, D. E. C.; Evrovski, J.; Forrest, Q.; Hutchison, S.; Holmes, K.; Ross, H. J. Pyridoxine improves endothelial function in cardiac transplant recipients. J. Heart Lung Transplant. 2001, 20, 964-969.
9. Haque, W. Cardioprotective Phosphonates and Malonates. WO Patent 0164692.
10. Blackburn, G. M.; Kent, D. E.; Kolkman, F. The synthesis and metal binding characteristics of novel, isopolar phosphonate analogues of nucleotides. J. Chem. Soc., Perkin Trans. 1 1984, 1119-1125.
11. Berkowitz, D. B.; Bose, M.; Pfannenstiel, T. J.; Doukov, T. α-Fluorinated phosphonates as substrate mimics for glucose 6-phosphate dehydrogenase: the CHF stereochemistry matters. J. Org. Chem. 2000, 65, 4498-4508.
12. O'Hagen, D.; Rzepa, H. S. Some influences of fluorine in bioorganic chemistry. J. Chem. Soc., Chem Commun. 1997, 645-652.
13. Denesyuk, A. I.; Denessiouk, K. A.; Korpela, T.; Johnson, M. S. Functional Attributes of the phosphate group binding cup of pyridoxal phosphate-dependent enzymes. J. Mol. Biol. 2002, 316, 155-172.
14. Hullar, T. L. Pyridoxal phosphate: I phosphonic acid analogues of pyridoxal phosphate. Synthesis via Wittig reactions and enzyme evaluation. J. Med. Chem. 1969, 12, 58-63.
15. Stirtan, W. G.; Withers, S. G. Phosphonate and α-fluorophosphonate analogue probes of the ionization state of pyridoxal 5′-phosphate (PLP) in glycogen. Biochemistry 1996, 35, 15057-15064.
16. Kim, Y.-C.; Camaioni, E.; Ziganshin, A. U.; Ji, X.-D.; King, B. F.; Wildman, S. S.; Rychkov, A.; Yoburn, J.; Kim, H.; Mohanram, A.; Harden, T. K.; Boyer, J. L.; Burnstock, G.; Jacobson, K. A. Synthesis and structure-activity relationships of pyridoxal-6-arylazo-5′-phosphate and phosphonate derivatives as P2 receptor antagonists. Drug Dev. Res. 1998, 45, 52-66.
17. Dhalla, N. S.; Sethi, R.; Dakshinamurti, K. Treatment of Cardiovascular and Related Pathologies. US Patent 6,043,259.
18. 6 analogues. Methods Enzymol. 1970, 18A, 524-566.
19. Brooks, H. G., Jr.; Laasko, J. W.; Metzler, D. E. Synthesis of vitamin B6 derivatives 1. Preparation of some isopyridoxamine derivatives from isopyridoxal. J. Heterocycl. Chem. 1966, 126-128.
20. Pudovik, A. N.; Konovalova, I. V. Addition reactions of esters of phosphorous III acids with unsaturated systems. Synthesis 1979, 81-96.
21. Ferrari, R.; Pepi, P.; Ferrari, F.; Nesta, F.; Benigno, M.; Visioli, O. Metabolic Derangement in Ischemic Heart Disease and its Therapeutic Control. Am. J. Cardiol. 1998, 82 (5A), 2K-13K.
22. Dellborg, M.; Herlitz, J.; Risenfors, M.; Swedberg, K. Electrocardiographic assessment of infarct size: comparison between QRS scoring of 12-lead electrocardiography and dynamic vector cardiography. Int. J. Cardiol. 1993, 40, 167-172.
23. Zacharowski, K.; Blackburn, B.; Thiemermann, C. Ranolazine, a partial fatty acid oxidation inhibitor, reduces myocardial infarct size and cardiac troponin C release in the rat. Eur. J. Pharmacol. 2001, 418, 105-110.
24. Kantor, P. F.; Dyck, J. R. B.; Lopaschuk, G. D. Fatty acid oxidation in the reperfused ischemic heart. Am. J. Med. Sci. 1999, 318, 3-14.
25. Lopaschuk, G. D. Optimizing cardiac energy metabolism: a new approach to treating ischemic heart disease. Eur. Heart J. Suppl. 1999, 1 (Suppl. O), O32-O39.
26. Bersin, R. M.; Stacpoole, P. W. Dichloroacetate as metabolic therapy for myocardial ischemia and failure. Am. Heart J. 1997, 134, 841-855.
27. Lopaschuk, G. D.; Barr, R. L. Measurement of fatty acid and carbohydrate metabolism in isolated working rat hearts. Mol. Cell Biochem. 1997, 172, 137-147.
28. Lopaschuk, G. D.; Wambolt, R. B.; Barr, R. L. An imbalance between glycolysis and glucose oxidation is a possible explanation for the detrimental effects of high levels of fatty acid during aerobic reperfusion of ischemic hearts. J. Pharmacol. Exp. Ther. 1993, 264, 135-144.