2,4-Diamino-5-methyl-6-substituted arylthio-furo[2,3-d]pyrimidines as novel classical and nonclassical antifolates as potential dual thymidylate synthase and dihydrofolate reductase inhibitors

Bioorganic and Medicinal Chemistry

Volumn 18, Issue 2, 2010, Pages 953-961

  Gangjee, Aleem ^a   Jain, Hiteshkumar D ^a   Phan, Jaclyn ^a   Guo, Xin ^a   Queener, Sherry F ^b   Kisliuk, Roy L ^c  

^a DUQUESNE UNIVERSITY   (United States)

^b INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c TUFTS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Dihydrofolate reductase; Dual inhibitors; Furo 2,3 d pyrimidines; Thymidylate synthase

Indexed keywords

2,4 DIAMINO 5 METHYL 6 (1 NAPHTHYLTHIO)FURO[2,3 D]PYRIMIDINE; 2,4 DIAMINO 5 METHYL 6 (2 NAPHTHYLTHIO)FURO[2,3 D]PYRIMIDINE; 2,4 DIAMINO 5 METHYL 6 (2' ISOPROPYL 6' METHYLPHENYLSULFANYL) FURO[2,3 D]PYRIMIDINE; 2,4 DIAMINO 5 METHYL 6 (2' METHOXYPHENYLSULFANYL) FURO[2,3 D]PYRIMIDINE; 2,4 DIAMINO 5 METHYL 6 (2',3',5',6' TETRAFLUORO 4' TRIFLUOROMETHYLPHENYLSULFANYL) FURO[2,3 D]PYRIMIDINE; 2,4 DIAMINO 5 METHYL 6 (2',5' DIMETHOXYPHENYLSULFANYL) FURO[2,3 D]PYRIMIDINE; 2,4 DIAMINO 5 METHYL 6 (2',6' DICHLOROPHENYLSULFANYL) FURO[2,3 D]PYRIMIDINE; 2,4 DIAMINO 5 METHYL 6 (2',6' DIMETHYLPHENYLSULFANYL) FURO[2,3 D]PYRIMIDINE; 2,4 DIAMINO 5 METHYL 6 (3',4' DIMETHOXYPHENYLSULFANYL FURO[2,3 D]PYRIMIDINE; 2,4 DIAMINO 5 METHYL 6 (4'METHOXYPHENYLSULFANYL) FURO[2,3 D]PYRIMIDINE; 2,4 DIAMINO 5 METHYL 6 SUBSTITUTED ARYLTHIO FURO[2,3 D]PYRIMIDINE; 2,4 DIAMINO 5 METHYL FURO[2,3 D]PYRIMIDINE; 4 [(2,4 DIAMINO 5 METHYL FURO[2,3 D]PYRIMIDIN 6 YL)THIO]BENZOIC ACID; DIETHYL N [4 [(2,4 DIAMINO 5 METHYL FURO[2,3 D]PYRIMIDIN 6 YL)THIO] BENZOYL] L GLUTAMATE; DIHYDROFOLATE REDUCTASE INHIBITOR; FOLIC ACID ANTAGONIST; IODINE; N [4 [(2,4 DIAMINO 5 METHYL FURO[2,3 D]PYRIMIDIN 6 YL) THIO] BENZOYL] L GLUTAMIC ACID; THIOPHENOL; THYMIDYLATE SYNTHASE; UNCLASSIFIED DRUG;

ARTICLE; DRUG ACTIVITY; DRUG DESIGN; DRUG POTENCY; DRUG SELECTIVITY; DRUG SYNTHESIS; MYCOBACTERIUM AVIUM; NONHUMAN; PATHOGENESIS; PNEUMOCYSTIS CARINII;

ANIMALS; CRYSTALLOGRAPHY, X-RAY; ENZYME INHIBITORS; ESCHERICHIA COLI; FOLIC ACID ANTAGONISTS; GLUTAMIC ACID; HUMANS; LIVER; MODELS, MOLECULAR; MOLECULAR STRUCTURE; MYCOBACTERIUM AVIUM; OXIDATION-REDUCTION; PNEUMOCYSTIS CARINII; PYRIMIDINES; RATS; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; TETRAHYDROFOLATE DEHYDROGENASE; THYMIDYLATE SYNTHASE; TOXOPLASMA;

MAMMALIA; MYCOBACTERIUM AVIUM; PNEUMOCYSTIS CARINII;

EID: 76449098088     PISSN: 09680896     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmc.2009.11.029     Document Type: Article

References (44)

1. Taken in part from the dissertation submitted by H.J. to the Graduate School of Pharmaceutical Sciences, Duquesne University, in partial fulfillment of the requirements for the degree of Doctor of Philosophy, July 2006.
2. Presented in part at the 228th American Chemical Society National Meeting, Philadelphia, PA, United States, August 22-26, 2004; Abstr. MEDI-101.
3. Schnell J.R., Dyson H.J., and Wright P.E. Annu. Rev. Biophys. Biomol. Struct. 33 (2004) 119
4. Berman E.M., and Werbel L.M. J. Med. Chem. 34 (1991) 479
5. Jackman A.L., Taylor G.A., Gibson W., Kimbell R., Brown M., Calvert A.H., Judson I.R., and Hughes L.R. Cancer Res. 51 (1991) 5579
6. Taylor E.C., Kuhnt D., Shih C., Rinzel S.M., Grindey G.B., Barredo J., Jannatipour M., and Moran R. J. Med. Chem. 35 (1992) 4450
7. Bertino J.R., Kamen B., and Romanini A. In: Holland J.F., Frei E., Bast R.C., Kufe D.W., WeichselbaumMorton D.L., and Weichselbaum R.R. (Eds). Cancer Medicine Vol. 1 (1997), Williams & Wilkins, Baltimore 907-921
8. Kisliuk R.L. Pharmacol. Ther. 85 (2000) 183
9. Boritzki T.J., Zhang C., Bartlett C.A., and Jackson R.C. In: Jackman A.L. (Ed). Antifolate Drugs in Cancer Therapy (1999), Humana Press, Totowa, New Jersey 281-292
10. Kisliuk R.L., Gaumont Y., Kumar P., Coutts M., Nair M.G., Nanavati N.T., and Kalman N.T. In: Goldman I.D. (Ed). Proceedings of the second workshop on folyl and antifolyl polyglutamates (1985), Praeger, New York 319-328
11. Kisliuk R.L., Gaumont Y., Powers J.F., Thorndike J., Nair M.G., and Piper J.R. In: Picciano M.F., Stokstad E.L.R., and Gregory III J.F. (Eds). Folic Acid Metabolism in Health and Disease (1990), Wiley, Liss, New York 79-89
12. Galivan J., Nimec Z., and Rhee M. Cancer Res. 47 (1987) 5256
13. Galivan J., Rhee M.S., Johnson T.B., Dilwith R., Nair M.G., Bunni M., and Priest D.G. J. Biol. Chem. 264 (1989) 10685
14. Gaumont Y., Kisliuk R.L., Emkey R., Piper J.R., and Nair M.G. In: Curtius H.-C., Blau N., and Ghisla S. (Eds). Chemistry and Biology of Pteridines (1990), de Gruyter, Berlin 1131-1136
15. Gaumont Y., Kisliuk R.L., Parsons J.C., and Greco W.R. Cancer Res. 52 (1992) 2228
16. Hynes J.B., Patil S.A., Tomazic A., Kumar A., Pathak A., Tan X., Li X., Ratnam M., Delcamp T.J., and Freisheim J.H. J. Med. Chem. 31 (1988) 449
17. Gangjee A., Yu J., McGuire J.J., Cody V., Galitsky N., Kisliuk R.L., and Queener S.F. J. Med. Chem. 43 (2000) 3837
18. Gangjee A., Lin X., Kisliuk R.L., and McGuire J.J. J. Med. Chem. 48 (2005) 7215
19. Gangjee A., Jain H.D., Phan J., Lin X., Song X., McGuire J.J., and Kisliuk R.L.D. J. Med. Chem. 49 (2006) 1055
20. Mendelsohn L.G., Shih C., Chen V.J., Habeck L.L., Gates S.B., and Shackelford K.A. Sem. Oncol. 26 (1999) 42
21. Rosowsky A. In: Ellis G.P., and West G.B. (Eds). Progress in Medicinal Chemistry Vol. 26 (1989), Elsevier Science, New York 1-252
22. Gangjee A., Elzein E., Kothare M., and Vasudevan A. Curr. Pharm. Des. 2 (1996) 263
23. Gangjee A., Devraj R., McGuire J.J., Kisliuk R.L., Queener S., and Barrows L.R. J. Med. Chem. 37 (1994) 1169
24. Gangjee A., Devraj R., McGuire J.J., and Kisliuk R.L. J. Med. Chem. 38 (1995) 3798
25. Tripos Inc., 1699 South Hanley Road, St. Louis, MO, 63144.
26. Sayre P.H., Finer-Moore J.S., Fritz T.A., Biermann D., Gates S.B., MacKellar W.C., Patel V.F., and Stroud R.M. J. Mol. Biol. 313 (2001) 813
27. Cody V., Luft J.R., and Pangborn W. Acta Crystallogr., Sect., D 61 (2005) 147
28. Jackson R.C. In: Jackman A.L. (Ed). Antifolate Drugs in Cancer Therapy (1999), Humana Press, Totowa, NJ 1-12
29. Grivsky E.M., Lee S., Sigel C.W., Duch D.S., and Nichol C.A. J. Med. Chem. 23 (1980) 327
30. Varney M.D., Marzoni G.P., Palmer C.L., Deal J.G., Webber S., Welsh K.M., Bacquet R.J., Bartlett C.A., Morse C.A., Booth C.L.J., Herrmann S.M., Howland E.F., Ward R.W., and White J. J. Med. Chem. 35 (1992) 663
31. Webber S.E., Bleckman T.M., Attard J., Deal J.G., Katherdekar V., Welsh K.M., Webber S., Janson C.A., Matthews D.A., Smith W.W., Freer S.T., Jordan S.R., Bacquet R.J., Howland E.F., Booth C.J.L., Ward R.W., Hermann S.M., White J., Morse C.A., Hilliard J.A., and Bartlett C.A. J. Med. Chem. 36 (1993) 733
32. Willemot P., and Klein M.B. Exp. Rev. Anti-Infect. Ther. 2 (2004) 521
33. Klepser M.E., and Klepser T.B. Drugs 53 (1997) 40
34. Chan D.C.M., and Anderson A.C. Curr. Med. Chem. 13 (2006) 377
35. Secrist J.A., and Liu III P.S.J. Org. Chem. 43 (1978) 3937
36. Beveridge S., and Harris R.L.N. Aust. J. Chem. 24 (1971) 1229
37. Gangjee A., Jain H.D., McGuire J.J., and Kisliuk R.L. J. Med. Chem. 47 (2004) 6730
38. Gangjee A., Jain H.D., Phan J., and Kisliuk R.L. J. Heterocycl. Chem. 42 (2005) 165
39. Gangjee A., Jain H.D., and Kisliuk R.L. Bioorg. Med. Chem. Lett. 15 (2005) 2225
40. Gangjee A., Jain H.D., and Queener S.F. J. Heterocycl. Chem. 42 (2005) 589
41. Taylor E.C., Patel H.H., and Jun J.-G. J. Org. Chem. 60 (1995) 6684
42. Kisliuk R.L., Strumpf D., Gaumont Y., Leary R.P., and Plante L. J. Med. Chem. 20 (1977) 1531
43. Wahba A.J., and Friedkin M. J. Biol. Chem. 237 (1962) 3794
44. Davisson V.J., Sirawaraporn W., and Santi D.V. J. Biol. Chem. 264 (1989) 9145