Project Start
1993-08-15
Project End
1996-08-14
Budget Start
1995-03-30
Budget End
1996-08-14
Support Year
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Pharmacology
Type
Schools of Medicine
DUNS #
005436803
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
Cody, Vivian; Luft, Joe R; Pangborn, Walt et al. (2004) Structure determination of tetrahydroquinazoline antifolates in complex with human and Pneumocystis carinii dihydrofolate reductase: correlations between enzyme selectivity and stereochemistry. Acta Crystallogr D Biol Crystallogr 60:646-55
Gangjee, Aleem; Adair, Ona O; Queener, Sherry F (2003) Synthesis and biological evaluation of 2,4-diamino-6-(arylaminomethyl)pyrido[2,3-d]pyrimidines as inhibitors of Pneumocystis carinii and Toxoplasma gondii dihydrofolate reductase and as antiopportunistic infection and antitumor agents. J Med Chem 46:5074-82
Cody, Vivian; Galitsky, Nikolai; Luft, Joseph R et al. (2002) Structure-based enzyme inhibitor design: modeling studies and crystal structure analysis of Pneumocystis carinii dihydrofolate reductase ternary complex with PT653 and NADPH. Acta Crystallogr D Biol Crystallogr 58:946-54
Nelson, R G; Rosowsky, A (2001) Dicyclic and tricyclic diaminopyrimidine derivatives as potent inhibitors of Cryptosporidium parvum dihydrofolate reductase: structure-activity and structure-selectivity correlations. Antimicrob Agents Chemother 45:3293-303
Cody, V; Chan, D; Galitsky, N et al. (2000) Structural studies on bioactive compounds. 30. Crystal structure and molecular modeling studies on the Pneumocystis carinii dihydrofolate reductase cofactor complex with TAB, a highly selective antifolate. Biochemistry 39:3556-64
Rosowsky, A; Papoulis, A T; Forsch, R A et al. (1999) Synthesis and antiparasitic and antitumor activity of 2, 4-diamino-6-(arylmethyl)-5,6,7,8-tetrahydroquinazoline analogues of piritrexim. J Med Chem 42:1007-17
Rosowsky, A; Cody, V; Galitsky, N et al. (1999) Structure-based design of selective inhibitors of dihydrofolate reductase: synthesis and antiparasitic activity of 2, 4-diaminopteridine analogues with a bridged diarylamine side chain. J Med Chem 42:4853-60
Rosowsky, A; Queener, S F; Cody, V (1999) Inhibition of dihydrofolate reductases from Toxoplasma gondii, Pneumocystis carinii, and rat liver by rotationally restricted analogues of pyrimethamine and metoprine. Drug Des Discov 16:25-40
Cody, V; Galitsky, N; Rak, D et al. (1999) Ligand-induced conformational changes in the crystal structures of Pneumocystis carinii dihydrofolate reductase complexes with folate and NADP+. Biochemistry 38:4303-12
Rosowsky, A; Papoulis, A T; Queener, S F (1998) 2,4-Diamino-6,7-dihydro-5H-cyclopenta[d]pyrimidine analogues of trimethoprim as inhibitors of Pneumocystis carinii and Toxoplasma gondii dihydrofolate reductase. J Med Chem 41:913-8

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