Quinazoline antifolate thymidylate synthase inhibitors: γ-linked L-D, D-D, and D-L dipeptide analogues of 2-desamino-2-methyl-N10-propargyl-5,8-dideazafolic acid (ICI 198583)

Journal of Medicinal Chemistry

Volumn 39, Issue 1, 1996, Pages 73-85

  Bavetsias, Vassilios ^a   Jackman, Ann L ^a   Kimbell, Rosemary ^a   Gibson, William ^a   Boyle, F Thomas ^b   Bisset, Graham M F ^a,c  

^a INSTITUTE OF CANCER RESEARCH   (United Kingdom)

^b ASTRAZENECA   (United Kingdom)

^c Cross Medical Ltd   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

2 DEAMINO 2 METHYL 10 PROPARGYL 5,8 DIDEAZAFOLIC ACID; DIPEPTIDE; ENZYME INHIBITOR; FOLIC ACID; FOLIC ACID ANTAGONIST; METHOTREXATE; QUINAZOLINE DERIVATIVE; THYMIDYLATE SYNTHASE; THYMIDYLATE SYNTHASE INHIBITOR; TRIFLUOROACETIC ACID;

ANIMAL CELL; ARTICLE; CELL GROWTH; CONTROLLED STUDY; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; GROWTH INHIBITION; HUMAN; HUMAN CELL; HYDROLYSIS; LEUKEMIA CELL; MOUSE; NONHUMAN;

ANIMALS; ANTINEOPLASTIC AGENTS; CELL DIVISION; DIPEPTIDES; FOLIC ACID; FOLIC ACID ANTAGONISTS; LEUKEMIA L1210; MAGNETIC RESONANCE SPECTROSCOPY; MASS SPECTROMETRY; MICE; MOLECULAR STRUCTURE; QUINAZOLINES; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; THYMIDYLATE SYNTHASE; TUMOR CELLS, CULTURED;

EID: 0030066361     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm950471+     Document Type: Article

References (45)

1. Sirotnak, F. M.; DeGraw, J. I. In Folate Antagonists as Therapeutic Agents; Sirotnak, F. M., Burchall, J. J., Ensminger, W. D., Montgomery, J. A., Eds.; Academic Press: New York, 1984; Vol. 2, pp 64-67.
2. Jackman, A. L.; Taylor, G. A.; Gibson, W.; Kimbell, R.; Brown, M.; Calvert, A. H.; Judson, I. R.; Hughes, L. R. ICI D1694, A Quinazoline Antifolate Thymidylate Synthase Inhibitor That is a Potent Inhibitor of L1210 Tumour Cell Growth In Vitro and In Vivo; A New Agent for Clinical Study. Cancer Res. 1991, 51, 5579-5586.
3. Jackman, A. L.; Farrugia, D. C.; Gibson, W.; Kimbell, R.; Harrap, K. R.; Stephens, T. C.; Azab, M.; Boyle, F. T. ZD1694 (Tomudex): A New Thymidylate Synthase Inhibitor With Activity in Colorectal Cancer. Eur. J. Cancer, in press.
4. Jackman, A. L.; Kelland, L. R.; Kimbell, R.; Brown, M.; Gibson, W.; Aherne, G. W.; Hardcastle, A.; Boyle, F. T. Mechanisms of Acquired Resistance to the Quinazoline Thymidylate Synthase Inhibitor ZD1694 (Tomudex) in one Mouse and Three Human Cell Lines. Br. J. Cancer 1995, 71, 914-924.
5. Pizzorno, G.; Chang, Y.-M.; McGuire, J. J.; Bertino, J. R. Inherent Resistance of Squamous Carcinoma Cell Lines to Methotrexate as a Result of Decreased Polyglutamation of This Drug. Cancer Res. 1989, 49, 5275-5280.
6. Cowan, K. H.; Jolivet, J. A. A Methotrexate Resistant Human Breast Cancer Cell Line with Multiple Defects Including Diminished Formation of MTX Polyglutamates. J. Biol. Chem. 1984, 259, 10793-10800.
7. Li, W. W.; Tong, W. P.; Waltham, M.; Bertino, J. R. Increased Folylpolyglutamate Hydrolase Activity as a Novel Mechanism of Natural Resistance to Methotrexate in a Human Soft Tissue Sarcoma Cell Line. Proc. Am. Assoc. Cancer Res. 1993, 34, Abstr. 1651.
8. Rhee, M. S.; Wang, Y.; Nair, M. G.; Galivan, J. Acquisition of Resistance to Antifolates Caused by Enhanced γ-Glutamyl Hydrolase Activity. Cancer Res. 1993, 53, 2227-2230.
9. McGuire, J. J.; Coward, J. K. Pteroylpolyglutamates: Biosynthesis, Degradation, and Function. In Folates and Pterins, Vol 1.; Blakley, R. L., Benkovie, S. J., Eds.; John Wiley & Sons: New York, 1984; pp 135-190 and references cited therein.
10. Sirotnak, F. M.; DeGraw, J. L In Folate Antagonists as Therapeutic Agents; Sirotnak, F. M., Burchall, J. J., Ensminger, W. D., Montgomery, J. A., Eds.; Academic Press: New York, 1984; Vol. 2, pp 86-89.
11. 10-propargl-5,8-dideazafolic acid (ICI 198583). J. Med. Chem. 1994, 37, 3294-3302.
12. Jodrell, D. I.; Gibson, W.; Bisset, G. M. F.; Boyle, F. T.; Judson, I. R.; Jackman, A. L. The In Vivo Metabolic Stability of Dipeptide Analogues of the Quinazoline Antifolate, ICI 198583, In Mice. Biochem. Pharmacol. 1993, 46, 2229-2234.
13. McGuire, J. J.; Hsieh, P.; Bertino, J. R.; Coward, J. K. Studies on the Substrate Specificity of Mammalian Folylpolyglutamate Synthetase. Chemistry and Biology of Pteridines; Walter de Gruyter & Co.: Berlin, 1983; pp 615-619.
14. 10-propargyl-5,8-dideazafolate as Antitumour Agents. In Advances in Experimental Medicine and Biology (Chemistry and Biology of Pteridines and Folates); Ayling, J. E., et al., Eds.; Plenum Press: New York, 1993; Vol. 338, pp 585-588.
15. Thornton, T. J.; Jackman, A. L.; Marsham, P. R.; O'Connor, B. M.; Bishop, J. A. M.; Calvert, A. H. Quinazoline Antifolate Thymidylate Synthase Inhibitors: Difluoro-Substituted Benzene Ring Analogues. J. Med. Chem. 1992, 35, 2321-2327.
16. (a) Godwin, H. A.; Rosenberg, I. H.; Ferenz, C. R.; Jacobs, P. M.; Meienhofer, J. The Synthesis of Biologically Active Pteroyloligo-γ-L-Glutamates (Folic Acid Conjugates). J. Biol. Chem. 1972, 247, 2266-2271.
17. (b) Meienhofer, J.; Jacobs, P. M.; Godwin, H. A.; Rosenberg, I. H. Synthesis of Hepta-γ-L-glutamic Acid by Conventional and Solid-Phase Techniques. J. Org. Chem. 1970, 35, 4137-4140.
18. Bisset, G. M. F.; Pawelczak, K.; Jackman, A. L.; Calvert, A. H.; Hughes, L. R. Syntheses and Thymidylate Synthase Inhibitory Activity of the Poly-γ-glutamyl Conjugates of N-[5-[N-(3,4-Dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N-methylamino]-2- thenoyl]-L-glutamic Acid (ICI D1694) and Other Quinazoline Antifolates. J. Med. Chem. 1992, 35, 859-866 and references cited therein.
19. Meinhofer, J. The Mixed Carbonic Anhydride Method of Peptide Synthesis. In The Peptides, Analysis, Synthesis, Biology; Gross, E., Meienhofer, J., Eds.; Academic Press: New York, 1985; Vol. 1, pp 264-309.
20. Kovacs, J.; Giannotti, R.; Kapoor, A. Polypeptides with Known Repeating Sequence of Amino Acids. Synthesis of Poly-L-glutamyl-L-alanyl-L-glutamic Acid and Polyglycylglycyl-L-phenylalanine through Pentachlorophenyl Active Esters. J. Am. Chem. Soc. 1966, 88, 2282-2292.
21. Rosowsky, A.; Forsch, R.; Uren, J.; Wick, M.; Kumar, A. A.; Freisheim, J. H. Methotrexate Analogues. 20. Replacement of Glutamate by Longer-Chain Amino Diacids: Effects on Dihydrofolate Reductase Inhibition, Cytotoxicity, and in Vivo Anti-tumor Activity. J. Med. Chem. 1983, 26, 1719-1724.
22. (a) Taschner, E.; Chimiak, A.; Bator, B.; Sokolowska, T. Preparation of tert-Butyl Esters of Free Amino Acids. Justus Liebigs Ann. Chem. 1961, 646, 133-136.
23. (b) The Practice of Peptide. Synthesis; Bodanszky, M., Bodanszky, A., Eds.; Springer-Verlag: Berlin, 1984; pp 48-49.
24. Rosowsky, A.; Forsch, R.; Uren, J.; Wick, M. Methotrexate Analogues. 14. Synthesis of New γ-Substituted Derivatives As Dihydrofolate Reductase Inhibitors and Potential Anticancer Agents. J. Med. Chem. 1981, 24, 1450-1455.
25. Hughes, L. R. Preparation of N-[[(quinazolinylmethyl)amino]-aroyl]amino Acids as Antitumor Agents. EP Pat. Appl. 284338 A2, 1988; Chem. Abstr. 1989, 110, 95797.
26. Marsham, P. R.; Jackman, A. L.; Barker, A. J.; Boyle, F. T.; Pegg, S. J.; Wardleworth, J. M.; Kimbell, R.; O'Connor, B. M.; Calvert, A. H.; Hughes, L. R. Quinazoline Antifolate Thymidylate Synthase Inhibitors: Replacement of Glutamic Acid in the C2-Methyl Series. J. Med. Chem. 1995, 38, 994-1004.
27. Taylor, E. C.; Fletcher, S. R.; Sabb, A. L. A. Convenient Synthesis of t-Butyl p-Aminobenzoate. Synth. Commun. 1984, 14 (10), 921-924.
28. Andrew, R. G.; Barker, A. J.; Boyle, F. T.; Wardleworth, J. M. Preparation of [(Quinasolinylmethyl)amino]benzamides and Related Compounds as Antitumour Agents. EP Pat. Appl. 459730 A2, 1991; Chem. Abstr. 1992, 116, 194334.
29. Hughes, L. R. Preparation of N-[[[(3,4-Dihydro-4-oxo-6-quinazolinyl)methyl]amino]aroyl]amino Acids as Antitumour Agents. EP Pat. Appl. 239362 A2, 1987; Chem. Abstr. 1988, 108, 205094.
30. Pawelczak, K.; Krzyzanowski, L.; Rzeszotarska, B. Improved Synthesis of Some α-Esters of N-Protected L-Glutamic Acid. Org. Prep. Proced. Int. 1985, 17, 416-419.
31. Boissonnas, R. A.; Guttmann, St.; Jaquenoud, P.-A.; Waller, J. P. A New Synthesis of Orytocin. Helv. Chim. Acta 1955, 38, 1491-1501.
32. Hanby, W. E.; Waley, S. G.; Watson, J. Synthetic polypeptides. Part II. Polyglutamic acid. J. Chem. Soc. 1950, 3239-3249.
33. (a) Camble, R.; Purkayastha, R.; Young, G. T. Amino-acids and Peptides. Part XXIX The Use of S-Benzylthiomethyl-L-cysteine in Peptide Synthesis: Synthesis of Glutathione and Homoglutathione. J. Chem. Soc. C 1968, 1219-1224.
34. (b) Thornton, T. J. Ph.D. Thesis, University of London, England, 1989.
35. 10-Propargyl-5,8-dideazafolic Acid (CB 3717): Development, Characterisation and Cross-Resistance Studies. Cancer Res. 1986, 46, 2810-2815.
36. 10-Propargyl-5,8-dideazafolic Acid (CB 3717) Polyglutamates in L1210 Cells in Vitro. Biochem. Pharmacol. 1988, 37, 4047-4054.
37. 10-propargyl-5,8-dideazafolic Acid and Related Compounds in Murine (L1210) and Human (W1L2) Systems In Vitro and L1210 in Vivo. Cancer Res. 1990, 50, 5212-5218.
38. Fry, D. W.; Besserer, J. A.; Boritzki, T. J. Transport of the Antitumour Antibiotic CI-90 in L1210 Leukemia Cells by the Reduced Folate Carrier System. Cancer Res. 1984, 44, 3366-3370.
39. Matthews, D. A.; Appelt, K.; Oatley, S.; Xuong, Ng, H. J. Crystal Structure of Escherichia coli Thymidylate Synthase Containing Bound 5-Fluoro-2′-deoxyuridylate and 10-Propargyl-5,8-dideazafolate. J. Mol. Biol. 1990, 214, 923-936.
40. Montfort, W. R.; Perry, K. M.; Fauman, E. B.; Finer-Moore, J. S.; Maley, G. F.; Hardy, L.; Maley, F.; Stroud, R. M. Structure, Multiple Site Binding, and Segmental Accommodation in Thymidylate Synthase on Binding dUMP and an Anti-Folate. Biochemistry 1990, 29, 6964-6977.
41. Jackman, A. L.; Kimbell, R.; Brown, M.; Brunton, L.; Bisset, G. M. F.; Bavetsias, V.; Marsham, P.; Hughes, L. R.; Boyle, F. T. Quinazoline-based Thymidylate Synthase Inhibitors: Relationship Between Structural Modifications and Polyglutamation. Anti-Cancer Drug Des., in press.
42. Kimbell, R.; Jackman, A. L.; Boyle, F. T.; Hardcastle, A.; Aherne, W. The Duration of the Inhibition of Thymidylate Synthase in Intact L1210 Cells Exposed to Two Different Classes of Quinazoline Analogues. In Advances in Experimental Medicine and Biology (Chemistry and Biology of Pteridines and Folates); Ayling, J. E., et al., Eds.; Plenum Press: New York, 1993; Vol. 338, pp 585-588.
43. 10-propargyl-5,8-dideazafolate As Antitumour Agents. In Advances in Experimental Medicine and Biology (Chemistry and Biology of Pteridines and Folates); Ayling, J. E., Nair, M. G., Baugh, C. M., Eds.; Plenum Press: New York, 1993; Vol. 338, pp 579-584.
44. Stephens, T. C.; Smith, M. N.; Waterman, S. E.; McCloskey, M. L.; Jackman, A. L.; Boyle, F. T. Use of Murine L5178Y Lymphoma Thymidine Kinase Mutants for In Vitro and In Vivo Antitumour Efficacy Evaluation of Novel Thymidylate Synthase Inhibitors. In Advances in Experimental Medicine and Biology (Chemistry and Biology of Pteridines and Palates); Ayling, J. E., Nair, M. G., Baugh, C. M., Eds.; Plenum Press: New York, 1993; Vol. 338, pp 589-592.
45. Hughes, L. R.; Jackman, A. L.; Oldfield, J.; Smith, R. C.; Burrows, K. D.; Marsham, P. R.; Bishop, J. A. M.; Jones, T. R.; O'Connor, B. M.; Calvert, A. H. Quinazoline Antifolate Thymidylate Synthase Inhibitors: Alkyl, Substituted Alkyl, and Aryl Substituants in the C2 Position. J. Med. Chem. 1990, 33, 3060-3067.