Synthesis of 2,4-diaminopteridines with bulky lipophilic groups at the 6-position as inhibitors of Pneumocystis carinii, Toxoplasma gondii, and mammalian dihydrofolate reductase

Pteridines

Volumn 8, Issue 3, 1997, Pages 173-187

  Rosowsky, Andre ^a   Forsch, Ronald A ^a   Queener, Sherry F ^b   Bertino, Joseph R ^c  

^a HARVARD MEDICAL SCHOOL   (United States)

^b INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

Author keywords

2,4 Diaminoptefidines; Bulky lipophilic group; Dihydrofolate reductase; Pneumocystis carinii; Toxoplasma gondii

Indexed keywords

ANTIPROTOZOAL AGENT; DIHYDROFOLATE REDUCTASE; DIHYDROFOLATE REDUCTASE INHIBITOR; METHOTREXATE; PTERIDINE DERIVATIVE;

ANTIPROTOZOAL ACTIVITY; ARTICLE; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG SYNTHESIS; ENZYME INHIBITION; HUMAN; HUMAN CELL; INFRARED SPECTROSCOPY; NONHUMAN; PNEUMOCYSTIS CARINII; PRIORITY JOURNAL; PROTON NUCLEAR MAGNETIC RESONANCE; RAT; STRUCTURE ACTIVITY RELATION; TOXOPLASMA GONDII;

MAMMALIA; PNEUMOCYSTIS CARINII; TOXOPLASMA GONDII;

EID: 0030666275     PISSN: 09334807     EISSN: 21954720     Source Type: Journal    
DOI: 10.1515/pteridines.1997.8.3.173     Document Type: Article

References (38)

1. Berman, E.M. & Werbel, L.M. J. Med. Chem. 1996; 39: 3621.
2. Masur, H.J. Infect. Dis. 1990; 161: 858.
3. Davoll, J., Johnson, A.M., Davies, H.J., Bird, O.D., Clarke, J. & Elslager, E.F. J. Med. Chem. 1972; 15: 812.
4. Elslager, E.F.; Johnson, J.J.; Werbel, L.M. J. Med. Chem. 1983; 26: 1753-1760.
5. Elslager, E.F.; Clarke, J.; Johnson, J.; Werbel, L.M.; Davoll, J. J. Heterocycl. Chem. 1972; 9: 759-773.
6. Elslager, E.F. & Davoll, J. Lectures in Heterocyclic Chemistry, Vol. 2. Castle, R.N. & Townsend, L.B., Eds., Hetero Corporation, Orem, Utah, 1974; p. S97.
7. Hynes, J.B., Ashton, W.T., Bryansmith, D. & Freisheim, J.H. J. Med. Chem. 1974; 17: 1023.
8. Hynes, J.B. & Ashton, W.T. J. Med. Chem. 1975; 18: 263.
9. Schornagel, J.H., Chang, P.K., Sciarini, L.J., Moroson, B.A., Mini, E., Cashmore, A.R. & Bertino, J.R. Biochem. Pharmacol. 1984; 33: 3551.
10. Gangjee A., Zaveri, N., Kothare, M. & Queener, S.F. J. Med. Chem. 1995; 38: 3660.
11. Gangjee A., Mavandadi, F., Queener, S.F. & McGuire, J.J. J. Med. Chem. 1995; 38: 2158.
12. Piper, J.R., Johnson, C.A., Krauth, C.A., Carter, R. L., Hosmer, C.A., Queener, S.F., Borotz, S.E. & Pfefferkorn, E.R. J. Med. Chem. 1996; 39: 1271.
13. Gangjee, A., Vasudevan, A., Queener, S.F. & Kisliuk, R.L. J. Med. Chem. 1996; 39: 1438.
14. Gangjee, A., Zhu, Y., Queener, S.F., Francom, P. & Broom, A.D. J. Med. Chem. 1996; 39: 1836.
15. Rosowsky A., Chen, K.K.N., Nadel, M.E., Papthanasopoulos, N. & Modest, E.J. J. Heterocycl. Chem. 1972; 9: 275.
16. Rosowsky, A., Chen, K.K.N., St. Amand, R. & Modest, E.J. J. Pharm. Sci. 1973; 62: 477.
17. Rosowsky, A., Huang, P.C., Papathanasopoulos, N. & Modest, E.J. J. Med. Chem. 1974; 17: 1217.
18. Taylor, E.C., Portnoy, R.C., Hochstetler, D.C. & Kobayashi, T. J. Org. Chem. 1975; 40: 2347; see also earlier references cited therein.
19. Taylor, E.C. & LaMattina, J.L. J. Org. Chem. 1977; 42: 1523.
20. Rosowsky, A. & Chen, K.K.N. J. Med. Chem. 1974; 17: 1308.
21. Broughton, M.C. & Queener, S.F. Antimicrob. Agents Chemother. 1991; 35: 1348.
22. Chio, L.-C. & Queener, S.F. Antimicrob. Agents Chemother. 1993; 37: 1914.
23. Bartlett, M.S., Shaw, M., Navaran, P., Smith, J.W. & Queener, S.F. Antimicrob. Agents Chemother. 1995; 39: 2436.
24. Rosowsky, A., Mota, C.E., Wright, J.E., Freisheim, J. H. Heusner, J.J., McCormack, J.J. & Queener, S.F. J. Med. Chem. 1993; 36: 3102.
25. Rosowsky, A., Mota, C.E., Wright, J.E. & Queener, S.F. J. Med. Chem. 1994; 37: 4522.
26. Rosowsky, A., Mota, C.E. & Queener, S.F. J. Heterocycl. Chem. 1995; 32: 335.
27. Rosowsky A., Mota, C.E., Queener, S.F., Waltham, M., Ercikan-Abali, E. & Bertino, J. R. J. Med. Chem. 1995; 38: 745.
28. Rosowsky, A., Forsch, R.A. & Queener, S.F. J. Med. Chem. 1995; 38: 2615.
29. Su, T.-L., Huang, J.-T., Chou, T.-C., Otter, G.M., Sirotnak, F.M. & Watanabe, K.A. J. Med. Chem. 1988; 31: 1209.
30. Rosowsky, A., Hynes, J.B. & Queener, S.F. Antimicrob. Agents Chemother. 1995; 39: 79.
31. Perrin, D.D. Advances in Heterocyclic Chemistry, Volume 4; Katritzky, A.R., Ed.; New York: Academic Press, 1965; p. 49.
32. Harris, N.V., Smith, C., & Bowden, K. J. Med. Chem. 1990; 33: 434.
33. Another possible explanation for the decreased binding of 2,4-pteridines relative to 2,4-diamino-5-deazapteridines is that a nitrogen atom at the 5-position abolishes an important hydrophobic contact to the enzyme, especially if this nitrogen were intramolecularly H-bonded to a molecule of water.
34. Kuyper, L.F., Baccanari, D.P., Jones, M.L., Hunter, R.N., Tansik, R.L., Joyner, S.S., Boytos, C.M., Rudolph, S.K., Knick, V., Wilson, H.R., Caddell, J.M., Friedman, H.S., Comley, J.C.W. & Stables, J.N. J. Med. Chem. 1996; 39: 892.
35. Cody, V., Wojtczak, A., Kalman, T.I., Freisheim, J. H. & Blakley, R.L. Adv. Exptl. Med. Biol. 1993; 338: 481.
36. Champness J.N., Achari, A., Ballantine, S.P., Bryant, P.K., Delves, C.J. & Stammers, D.K. Structure 2, 1994; 915.
37. Roos, D.S. J. Biol. Chem. 1993; 268: 6269.
38. Rosowsky, A., Battaglia, J., Chen, K.K.N., Papathanasopoulos, N. & Modest, E.J. J. Chem. Soc. (C), 1969; 1376.