Design, synthesis, and x-ray crystal structure of a potent dual inhibitor of thymidylate synthase and dihydrofolate reductase as an antitumor agent

Journal of Medicinal Chemistry

Volumn 43, Issue 21, 2000, Pages 3837-3851

  Gangjee, A ^a   Yu, J ^a   McGuire, J J ^b   Cody, V ^c   Galitsky, N ^c   Kisliuk, R L ^d   Queener, S F ^e  

^a DUQUESNE UNIVERSITY   (United States)

^b ROSWELL PARK CANCER INSTITUTE   (United States)

^c HAUPTMAN WOODWARD MEDICAL RESEARCH INSTITUTE   (United States)

^d TUFTS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^e INDIANA UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; DIHYDROFOLATE REDUCTASE INHIBITOR; GLUTAMIC ACID DERIVATIVE; N [2 AMINO 4 METHYL[(PYRROLO[2,3 D]PYRIMIDIN 5 YL)ETHYL]BENZOYL] GLUTAMIC ACID; PYRIDINE DERIVATIVE; THYMIDYLATE SYNTHASE INHIBITOR; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER CELL CULTURE; CRYSTAL STRUCTURE; DRUG DESIGN; DRUG EFFECT; DRUG SCREENING; DRUG SYNTHESIS; ESCHERICHIA COLI; HUMAN; HUMAN CELL; LACTOBACILLUS CASEI; PNEUMOCYSTIS CARINII; TOXOPLASMA GONDII; X RAY CRYSTALLOGRAPHY;

ANIMALS; ANTINEOPLASTIC AGENTS; CRYSTALLOGRAPHY, X-RAY; DRUG DESIGN; DRUG SCREENING ASSAYS, ANTITUMOR; ENZYME INHIBITORS; ESCHERICHIA COLI; FOLIC ACID ANTAGONISTS; GLUTAMIC ACID; HUMANS; LACTOBACILLUS CASEI; MODELS, MOLECULAR; PNEUMOCYSTIS; PYRIMIDINES; RATS; STRUCTURE-ACTIVITY RELATIONSHIP; TETRAHYDROFOLATE DEHYDROGENASE; THYMIDYLATE SYNTHASE; TOXOPLASMA; TUMOR CELLS, CULTURED;

EID: 0034687229     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm000200l     Document Type: Article

References (87)

1. The renewed potential for folate antagonists in contemporary cancer chemotherapy
2. Eukaryotic dihydrofolate reductase
3. Biogenesis and interconversion of substituted tetrahydrofolates
4. Catalytic mechanism and structure of thymidylate synthase
5. Fluoropyrimidines as antifolate drugs
6. Tomudex (ZD1694): From concept to care, a program in rational drug discovery
7. Folate antagonists
8. Antifolates in clinical development
9. A phase I study of the lipophilic thymidylate synthase inhibitor Thymitac(tm) (Nolatrexed dihydrochloride) given by 10-day oral administration
10. Chemistry and biological activity of antifolates
11. Classical and nonclassical antifolates as potential antitumor, antipneumocystis and antitoxoplasma agents
12. A potent antitumor quinazoline inhibitor of thymidylate synthase: Synthesis, biological properties and therapeutic results in mice
13. The effect of polyglutamylation on the inhibitory activity of folate analogues
14. Synergistic growth inhibition by combination of antifolates
15. Synergistic growth inhibition of rat hepatoma cells exposed in vitro to n-10-propargyl-5,8-dideazafolate with methotrexate or the lipophilic antifolates trimetrexate or meteprine
16. The role of cellular folates in the enhancement of activity of the thymidylate synthase inhibitor 10-propargyl-5,8-dideazafolate against hepatoma cells in vitro by inhibitors of dihydrofolate reductase
17. Folate enhancement of antifolate synergism in human lymphoma cells
18. Quanatitation of folic acid enhancement of antifolate synergism
19. Inhibition of murine thymidylate synthase and human dihydrofolate reductase by 5,8-dideaza analogues of folic acid and aminopterin
20. Classical and nonclassical Furo[2,3-d]-pyrimidines as novel antifolates: Synthesis and biological activities
21. Effect of bridge region variation on antifolate and antitumor activity of classical 5-substituted 2,4-Diminofuro[2,3-d]pyrimidines
22. MTA: Summary and conclusions
23. Novel Pyrrolo-[2,3-d]pyrimidine antifolates: Synthesis and antitumor activities
24. Pyrrolo[2,3-d]pyrimidines and Pyrido[2,3-d]pyrimidines as conformationally restricted analogues of the antibacterial agent trimethoprim
25. Crystal structure of Escherichia coli thymidylate synthase containing bound 5-Fluoro-2'-Deoxyuridylate and 10-Propargyl-5,8-Dideazafolate
26. Binding of the anticancer drug ZD1694 to E. coli thymidylate synthase: Assessing specificity and affinity
27. Design of thymidylate synthase inhibitors using protein crystal structures: The synthesis and biological evaluation of a novel class of 5-substituted quinazolinones
28. Design of enzyme inhibitors using iterative protein crystallographic analysis
29. Crystal structure-based design and synthesis of Benz-[cd]indole-containing inhibitors of thymidylate synthase
30. Design and synthesis of novel 6,7-Imidazotetrahydroquinoline inhibitors of thymidylate synthase using iterative protein crystal structure analysis
31. 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
32. A dideazatetrahydrofolate analogue lacking a chiral center at C-6, N-[4-[2-(2-Amino-3,4-dihydro-4-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]-ben zoyl]-L-glutamate Acid, Is an inhibitor of thymidylate synthase
33. Polyglutamylation of the Thymidylate Synthase (TS) inhibitor, ICI D1694
34. 10-Propargyl-5,8-dideazafolic acid (CB 3717) polyglutamations in L1210 cells in vitro
35. 10-propargyl-5,8-dideazafolic acid (ICI 198583)
36. Polyglutamylation as a determinate of cytotoxicity of classical folate analogue inhibitors of thymidylate synthase and glycinamide ribonucleotide formyltransferase
37. 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-th enoyl]-L-glutamic acid (ICI d1694) and other quinazoline antifolates
38. 10-propargyl-5,8-dideazafolic acid (ICI 198583)
39. ICI D1694 resistant cell lines
40. Intrinsic resistance of squamous cell carcinoma cell lines as a result of decreased accumulation of intracellular methotrexate polyglutamates
41. Decreased folylpolyglutamate synthetase activity as a mechanism of methotrexate resistance in CCRF-CEM human leukemia sublines
42. Importance of pharmacodynamics in the in vitro antiproliferative activity of the antifolates methotrexate and 10-edam against head and neck squamous cell carcinoma
43. A novel synthetic route to 7-Substituted derivatives of the antitumor agent LY231514 (MTX)
44. Synthesis and in vitro evaluation of some new pyrimidines and related condensed ring systems as potential anticancer agents
45. Synthesis of 2-Amino-6,7-dihydrothieno[3',2':5,6]pyrido[2,3-d]pyrimidine-4-one
46. Rapid removal of protecting groups from peptides by catalytic transfer hydrogenation with 1,4-Cyclohexadiene
47. Enantioselective total synthesis of cis-Trikentrin B
48. Rapid debenzylation of N-benzylamino derivatives to amino-derivatives using ammonium formate as catalytic hydrogen transfer agent
49. Nucleosides. XVII. Benzylationdebenzylatlon studies on nucleosides
50. A new synthesis of Pyrrolo[3,2-d]pyrimidines ('9-Deazapurines') via 3-Amino-2-carboalkoxy pyrroles
51. 6-Amino-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (3,7-Dideaza-guanine)
52. Synthesis of a novel Pyrrolo[2,3-d]pyrimidine alkaloid, rigidin
53. Synthesis of the marine dibromooxoindoline convolutamydine C
54. The synthesis and determination of acidic ionization constants of certain 5-substituted 2-Aminopyrrolo[2,3-d]pyrimidin-4-ones and methylated analogues
55. The synthesis of N-{2-Amino-4-substituted[(pyrrolo[2,3-d]-pyrimidin-5-yl)ethyl]benzoyl}-L-gl utamate acids as antitumor agents
56. Synthesis of a regioisomer of N-{4-[2-(2-amino-4(3H)-oxo-7H-pyrrolo-[2,3-d]pyrimidin-5-yl)ethyl]benzoyl}- L-glutamic acid (LY231514), an active thymidylate synthase inhibitor and antitumor agent
57. A convenient synthesis of acetylenes: Catalytic substitutions of acetylenic hydrogen with bromoalkenes, iodoarenes, and bromopyridines
58. Convergent and efficient palladium-effected synthesis of 5,10-Dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF)
59. 88. 7-Substituted 7-Deaza-2'-deoxyguanosines: Regioselective halogenation of Pyrrolo[2,3-d]pyrimidine nucleosides
60. Comparison of ternary complexes of Pneumocystis carinii and wild-type human dihydrofolate reductase with a novel classical antitumor Furo-[2,3-d]pyrimidine antifolate
61. +
62. Structure determination of lipophilic 5-Adamantyl diaminopyrimidine anticancer agents as cofactor ternary complexes with human and Pneumocystis carinii dihydrofolate reductase
63. ICI D1694, a quinazoline antifolate thymidylate synthase inhibitor that is a potent inhibitor of L1210 tumor cell growth in vitro and in vivo: A new agent for clinical study
64. LY231514, a Pyrrolo[2,3-d]pyrimidine-based antifolate that inhibits multiple folate-requiring enzyme
65. Pteroylpolyglutamates: Biosynthesis, degradation and function
66. Continuous culture of lymphoblasts from peripheral blood of a child with acute leukemia
67. Molecular and karyological analysis of methotrexate-resistant and -sensitive human leukemic CCRF-CEM cells
68. Effects of methotrexate esters and other lipophilic antifolates on methotrexate-resistant human leukemic lymphoblasts
69. Decreased folypolyglutamate synthetase activity as a mechanism of methotrexate resistance in CCRF-CEM human leukemia sublines
70. Thymidylate synthase as a target for growth inhibition in methotrexate-sensitive and -resistant human head and cancer and leukemia cell lines
71. Thymidine induced perturbations in ribonucleoside and deoxyribonucleoside triphosphate pools in human leukemic CCRF-CEM Cells
72. Purification and properties of human cytosolic folylpolygamma-glutamate synthetase and organization, localization,and differential splicing of its gene
73. In vitro methotrexate polyglutamate synthesis by rat liver folylpolyglutamate synthstase and its inhibition by bromosulfophthalein
74. Isolation and expression of the Pneumocystis carinii dihydrofolate reductase gene
75. Primary structure and expression of the dihydropteroate synthetase gene of Plasmodium falciparum
76. Microbatch macromolecular crystal growth techniques
77. Processing of X-ray diffraction data collected in oscillation mode
78. CHAIN-A crystallographic modeling program
79. PROCHECK: A program to check the stereochemical quality of protein structure