Synthesis and enzymic evaluation of 4-mercapto-6-oxo-1,4- azaphosphinane-2-carboxylic acid 4-oxide as an inhibitor of mammalian dihydroorotase

Journal of Medicinal Chemistry

Volumn 41, Issue 23, 1998, Pages 4550-4555

  Manthey, Michael K ^a   Huang, Danny T C ^a   Bubb, William A ^a   Christopherson, Richard I ^a  

^a UNIVERSITY OF SYDNEY   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

4 MERCAPTO 6 OXO 1,4 AZAPHOSPHINANE 2 CARBOXYLIC ACID 4 OXIDE; CARBOXYLIC ACID DERIVATIVE; DIHYDROOROTASE; UNCLASSIFIED DRUG;

ARTICLE; CATALYSIS; CHELATION; COMPLEX FORMATION; CYCLIZATION; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; ENZYME ACTIVE SITE; ENZYME ANALYSIS; ENZYME INHIBITION; MOLECULAR INTERACTION; NONHUMAN; RECEPTOR AFFINITY;

ANIMALS; CRICETINAE; CYCLIC N-OXIDES; DIHYDROOROTASE; ENZYME INHIBITORS; ESCHERICHIA COLI; HETEROCYCLIC COMPOUNDS; RECOMBINANT PROTEINS; STEREOISOMERISM;

EID: 0032487937     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm970814z     Document Type: Article

References (19)

1. Christopherson, R. I.; Jones, M. E. The Effects of pH and Inhibitors upon the Catalytic Activity of the Dihydroorotase of Multi Enzymatic Protein pyr 1-3 from Mouse Ehrlich Ascites Carcinoma. J. Biol. Chem. 1980, 255, 3358-3370.
2. Walsh, C. Enzymatic Reaction Mechanisms. W. H. Freeman: San Francisco, 1979; p 104-107.
3. Brooke, J.; Szabados, E.; Lyons, S. D.; Goodridge, R. J.; Harsanyi, M. C.; Poiner, A.; Christopherson, R. I. Cytotoxic Effects of Dihydroorotase Inhibitors upon Human CCRF-CEM Leukaemia. Cancer Res. 1990, 50, 7793-7798.
4. Seymour, K. K.; Lyons, S. D.; Phillips, L.; Rieckmann, K. H.; Christopherson, R. I. Cytotoxic Effects of Inhibitors of de novo Pyrimidine Biosynthesis upon Plasmodium Falciparum. Biochemistry 1994, 33, 5268-5274.
5. Christopherson, R. I.; Schmalzl, K. J.; Sharma, S. C. Enzyme Inhibitors. 1987, Complete Patent Specification: Australia 77692/87, Japan 220095/87, U.S.A. 091,761, South Africa 87/ 6552, Europe 87307744.0.
6. Williams, N. K.; Manthey, M. K.; Hambley, T. W.; O'Donoghue, S. I.; Keegan, M.; Chapman, B. E.; Christopherson, R. I. Catalysis by Hamster Dihydroorotase: Zinc Binding, Site Directed Mutagenesis and Interaction with Inhibitors. Biochemistry 1995, 34, 11344-31352.
7. Adams, J. L.; Meek, T. D.; Mong, S.-M.; Johnson, R. K.; Metcalf, B. W. cis-4-Carboxy-6-(mercaptomethyl)-3,4,5,6-tetrahydropyrimidin-2(1H)-one, a Potent Inhibitor of Mammalian Dihydroorotase. J. Med. Chem. 1988, 31, 1355-1359.
8. Levenson, C. H.; Meyer, R. B. Design and Synthesis of Tetrahedral Intermediate Analogues as Potential Dihydroorotase Inhibitors. J. Med. Chem. 1984, 27, 228-232.
9. Christopherson, R. I.; Schmalzl, K. J.; Szabados, E.; Goodridge, R. J.; Harsanyi, M. C.; Sant, M. E.; Algar, E. M.; Anderson, J. E.; Armstrong, A.; Sharma, S. C.; Bubb, W. A.; Lyons, S. D. Mercaptan and Dicarboxylate Inhibitors of Hamster Dihydroorotase. Biochemistry 1989, 28, 463-470.
10. Cao, Y.; Christopherson, R. I.; Elix, J. A.; Gaul, K. L. Synthesis of a Phosphinic Acid Transition State Analogue Inhibitor of Dihydroorotase. Aust. J. Chem. 1994, 47, 903-911.
11. Rickelton, W. A.; Boyle, R. J. The Selective Recovery of Zinc with New Thiophosphinic Acids. Solvent Extr. Ion. Exch. 1990, 8, 783-797.
12. Wagner, R.; Berger, S. Gradient-Selected NOESY - A Fourfold Reduction of the Measurement Time for the NOESY Experiment. J. Magn. Reson. 1996, 123A, 119-121.
13. Günther, H. NMR Spectroscopy - An Introduction. Wiley: Chichester, 1980; p 160-170.
14. Sternhell, S. Correlation of Interproton Spin-Spin Coupling Constants with Structure. Q. Rev. Chem. Soc. 1969, 236-270.
15. Shandruk, M. I.; Yanchuk, N. I.; Grekov, A. P. Hydrazides of Phosphinic and Phosphoric Acids. Zh. Obshch. Khim. 1973, 43, 2194-2198.
16. Miller, J. B. Preparation of Crystalline Diphenyldiazomethane. J. Org. Chem. 1959, 24, 560-561.
17. Klenk, M. M.; Suter, C. M.; Archer, S. The Preparation and Properties of Some Benzohydryl Sulfones. J. Am. Chem. Soc. 1948, 70, 3846-3850.
18. Miller, R. C.; Bradley, J. S.; Hamilton, L. A. Disubstitiuted Phosphine Oxides III. Addition to α,β-Unsaturated Nitriles and Carbonyl Compounds. J. Am. Chem. Soc. 1956, 78, 5299-5303.
19. Duggleby, R. G. Regression analysis of nonlinear Arrhenius plots: an empirical model and computer program. Comput. Biomed. Res. 1984, 14, 447-455.