In vitro metabolic transformations of 2,4-dipyrrolidinylpyrimidine: A chemical probe for P450-mediated oxidation of tirilazad mesylate

Xenobiotica

Volumn 27, Issue 11, 1997, Pages 1131-1145

  Streeper, R T ^a,b   Pearson, P G ^a   Zhao, Z ^a   Mizsak, S A ^a   Sanders, P E ^a   Wienkers, L C ^a   Vrbanac, J J ^a  

^a PFIZER INC   (United States)

^b SOUTHWEST RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2,4 DIPYRROLIDINYLPYRIMIDINE; CYTOCHROME P450; PYRIMIDINE DERIVATIVE; TIRILAZAD; UNCLASSIFIED DRUG;

ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; ENZYME ACTIVITY; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HYDROXYLATION; IN VITRO STUDY; ISOTOPE LABELING; LIVER METABOLISM; LIVER MICROSOME; MALE; MASS SPECTROMETRY; NONHUMAN; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; RAT; REACTION ANALYSIS;

ANIMALS; ANTIOXIDANTS; BIOTRANSFORMATION; CHROMATOGRAPHY, LIQUID; CYANIDES; CYTOCHROME P-450 ENZYME SYSTEM; DEUTERIUM; FREE RADICAL SCAVENGERS; HYDROXYLATION; MALE; MASS SPECTROMETRY; OXIDATION-REDUCTION; PREGNATRIENES; PYRIMIDINES; PYRROLES; RATS; RATS, SPRAGUE-DAWLEY;

ANIMALIA;

EID: 0030723930     PISSN: 00498254     EISSN: None     Source Type: Journal    
DOI: 10.1080/004982597239895     Document Type: Article

References (21)

1. ANDERSON, D. K., BRAUGHLER, J. M., HALL, E. D., WATERS, T. R., MCCALL, J. M. and MEANS, E. D., 1988, Effect of treatment with U-74006F on neurological outcome following experimental model of spinal cord injury. Journal of Neurosurgery, 96, 562-567.
2. BERNARD, T., 1995a, Monooxygenase-catalyzed nitrogen oxidations. In Biochemistry of Redox Reactions, edited by B. Testa and J. Caldwell (New York: Academic), pp. 164-202.
3. BERNARD, T., 1995, Monooxygenase-catalyzed N-C cleavage. In Biochemistry of Redox Reactions, edited by B. Testa and J. Caldwell (New York: Academic), pp. 203-234.
4. BRAUGHLER, J. M., BURTON, P. S., CHASE, R. L., PREGENZER, J. G., JACOBSON, E. J., VANDOORNICK, F. K. J., TUSTIN, J. M., AYER, D. E. and BUNDY, G. L., 1988, Novel membrane localized inhibitors of iron-dependent lipid peroxidation. Biochemical Pharmacology, 37, 3853-3860.
5. BRAUGHLER, J. M., HALL, E. D., JACOBSON, E. J., MCCALL, J. M. and MEANS, E. D., 1989, The 21-aminosteroids : potent inhibitors of lipid peroxidation for the treatment of central nervous system trauma and ischemia. Drugs Future, 14, 143-152.
6. FLEISHAKER, J. C., PETERS, G. R. and CATHCART, K. S., 1993a, Evaluation of the pharmacokinetics and tolerability of tirilazad mesylate, a 21-aminosteroid free radical scavenger: I. Single dose administration. Journal of Clinical Pharmacology, 13, 175-181.
7. FLEISHAKER, J. C., PETERS, G. R., CATHCART, K. S. and STEENWYK, R. C., 1993b, Evaluation of the pharmacokinetics and tolerability of tirilazad mesylate, a 21-aminosteroid free radical scavenger: II. Multiple dose administration. Journal of Clinical Pharmacology, 33, 182-190.
8. HALL, E. D., YONKERS, P. A., MCCALL, J. M. and BRAUGHLER, J. M., 1988a, Effects of the 21-aminosteroid U-74006F on experimental head injury in mice. Journal of Neurosurgery, 68, 456-461.
9. HALL, E. D., BERRY, K. P. and BRAUGHLER, J. M., 1988b, The 21-aminosteroid lipid peroxidation inhibitor U-74006F protects against cerebral ischemia in gerbils. Stroke, 19, 997-1002.
10. HOLSZTYNSKA, E. J. and DOMINO, E. F., 1986, Biotransformations of phencyclidine. Drug Metabolism Reviews, 16, 285-320.
11. KANAMURA, K., WEIR, B. K. A., FINDALY, J. M., GRACE, M. and MACDONALD, R. L., 1990, A dosage study of the effect of the 21-aminosteroid U-74006F on chronic cerebral vasospasm in a primate model. Neurosurgery, 27, 29-38.
12. KASSELL, N. F., HALEY, E. L. and ALVES, W., 1993, Phase II trial of tirilazad in aneurysmal subarachnoid hemorrhage. Canadian Journal of Neurological Science, 20 (suppl. 1), S29.
13. KYEREMATEN, G. A. and VESELL, E. S., 1991, Metabolism of nicotine. Drug Metabolism Review, 33, 3-41.
14. MARET, G., TESTA, B., JENNER, P., TAYAR, N. E. and CARRUPT, P.-A., 1990, The MPTP story: MAO activates tetrahydropyridine derivatives to toxins causing parkinsonism. Drug Metabolism Reviews, 22, 291-332.
15. MASUMOTO, H., OHTA, S. and HIROBE, M., 1991, Application of chemical cytochrome P-450 model systems to studies on drug metabolism. IV. Mechanism of piperidine metabolism pathways via an iminium intermediate. Drug Metabolism and Disposition, 19, 768-780.
16. ORTIZ DE MONTELLANO, P. R., 1989, Cytochrome P-450 catalysis: radical intermediates and dehydration reactions. TiPS, 10, 354-359.
17. ORTIZ DE MONTELLANO, P. R. and STEARNS, R. A., 1989, Radical intermediates in the cytochrome P-450-catalyzed oxidation of aliphatic hydrocarbons. Drug Metabolism Reviews, 20, 183-191.
18. STOTHERS, J. B., 1972, Carbon-13 NMR Spectroscopy (New York: Academic).
19. STREEPER, R. T., PEARSON, P. G., ZHAO, Z., MIZSAK, S. A. and VRBANAC, J. J., 1997, Synthesis of deuterium labeled 2,4-dipyrrolidinylpyrimidine as a chemical probe for P450 mediated oxidation of tirilazad mesylate. Journal of Labelled Compounds and Radiopharmacology (under revision).
20. 4-5α-reductase. Drug Metabolism and Disposition, 23, 383-392.
21. WIENKERS, L. C., STEENWYK, R. C., SANDERS, P. E., and PEARSON, P. G., 1996, Biotransformation of tirilazad in human: 1. Cytochrome P450 3A-mediated hydroxylation of tirilazad mesylate in human liver microsomes. Journal of Pharmacology and Experimental Therapeutics, 277, 982-990.