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Dihydrofolate reductase
A dihydrofolate reductase folA that is encoded in the genome of Escherichia coli K-12. [PRO:DNx, UniProtKB:P0ABQ4]
Synonyms
EC 1.5.1.3
Research
Bioassay Publications (54)
| Timeframe | Studies on this Protein(%) | All Drugs % |
|---|
| pre-1990 | 15 (27.78) | 18.7374 |
| 1990's | 10 (18.52) | 18.2507 |
| 2000's | 23 (42.59) | 29.6817 |
| 2010's | 6 (11.11) | 24.3611 |
| 2020's | 0 (0.00) | 2.80 |
Compounds (30)
Drugs with Inhibition Measurements
| Drug | Taxonomy | Measurement | Average (mM) | Bioassay(s) | Publication(s) |
|---|
| lamotrigine | Escherichia coli K-12 | IC50 | 348.9000 | 1 | 1 |
| lamotrigine | Escherichia coli K-12 | Ki | 15.2400 | 1 | 1 |
| methazolamide | Escherichia coli K-12 | IC50 | 0.0140 | 1 | 1 |
| pyrimethamine | Escherichia coli K-12 | IC50 | 4.3000 | 2 | 2 |
| pyrimethamine | Escherichia coli K-12 | Ki | 0.0636 | 5 | 5 |
| imatinib | Escherichia coli K-12 | IC50 | 0.3720 | 1 | 1 |
| trimethoprim | Escherichia coli K-12 | IC50 | 265.3383 | 32 | 45 |
| trimethoprim | Escherichia coli K-12 | Ki | 0.0017 | 8 | 8 |
| trimetrexate | Escherichia coli K-12 | IC50 | 0.1798 | 8 | 11 |
| cycloguanil | Escherichia coli K-12 | IC50 | 20.9100 | 1 | 1 |
| cycloguanil | Escherichia coli K-12 | Ki | 1.0200 | 1 | 1 |
| 4,6-diamino-2,2-dimethyl-1,2-dihydro-1-phenyl-s-triazine | Escherichia coli K-12 | Ki | 15.6060 | 2 | 2 |
| diaveridine | Escherichia coli K-12 | IC50 | 0.0707 | 3 | 3 |
| diaveridine | Escherichia coli K-12 | Ki | 0.0190 | 1 | 1 |
| piritrexim | Escherichia coli K-12 | IC50 | 0.0244 | 5 | 5 |
| 2,4-diaminoquinazoline | Escherichia coli K-12 | IC50 | 100,000.0000 | 1 | 1 |
| tetroxoprim | Escherichia coli K-12 | IC50 | 0.0180 | 1 | 1 |
| tetroxoprim | Escherichia coli K-12 | Ki | 0.0045 | 1 | 1 |
| brodimoprim | Escherichia coli K-12 | IC50 | 0.0030 | 1 | 1 |
| brodimoprim | Escherichia coli K-12 | Ki | 0.0006 | 1 | 1 |
| epiroprim | Escherichia coli K-12 | IC50 | 2.6000 | 1 | 1 |
| methylbenzoprim | Escherichia coli K-12 | IC50 | 0.9000 | 1 | 1 |
| 2,4-diamino-5-benzylpyrimidine | Escherichia coli K-12 | IC50 | 2.6691 | 2 | 2 |
| 2,4-diamino-5-benzylpyrimidine | Escherichia coli K-12 | Ki | 0.6607 | 1 | 1 |
| 2,4-diamino-5,6-dihydro-6,6-dimethyl-5-(4'-methoxyphenyl)-s-triazine | Escherichia coli K-12 | IC50 | 89.1000 | 1 | 1 |
| 2,4-diamino-5,6-dihydro-6,6-dimethyl-5-(4'-methoxyphenyl)-s-triazine | Escherichia coli K-12 | Ki | 4.0200 | 1 | 1 |
| methotrexate | Escherichia coli K-12 | IC50 | 4.1688 | 24 | 34 |
| methotrexate | Escherichia coli K-12 | Ki | 34.5460 | 5 | 5 |
| aminopterin | Escherichia coli K-12 | IC50 | 0.0110 | 1 | 1 |
| iclaprim | Escherichia coli K-12 | IC50 | 50.4048 | 2 | 6 |
| n-(3-chloro-7-indolyl)-1,4-benzenedisulphonamide | Escherichia coli K-12 | IC50 | 0.0070 | 1 | 1 |
| pd 173955 | Escherichia coli K-12 | IC50 | 0.0280 | 1 | 1 |
| raltitrexed | Escherichia coli K-12 | IC50 | 12.4100 | 3 | 8 |
| n-(4(n-((2-amino-4-hydroxy-6-quinazolinyl)methyl)prop-2-ynylamino)benzoyl)-l-glutamic acid | Escherichia coli K-12 | IC50 | 23.0000 | 2 | 2 |
| 1843u89 | Escherichia coli K-12 | IC50 | 20.0000 | 1 | 1 |
| pemetrexed | Escherichia coli K-12 | IC50 | 383.5250 | 12 | 12 |
| cb 3717 | Escherichia coli K-12 | IC50 | 5.5309 | 5 | 20 |
Drugs with Activation Measurements
Drugs with Other Measurements
| Drug | Taxonomy | Measurement | Average (mM) | Bioassay(s) | Publication(s) |
|---|
| pyrimethamine | Escherichia coli K-12 | Ratio | 0.0009 | 4 | 4 |
Novel tricyclic indeno[2,1-d]pyrimidines with dual antiangiogenic and cytotoxic activities as potent antitumor agents.Bioorganic & medicinal chemistry, , Jul-15, Volume: 20, Issue:14, 2012
The effect of 5-alkyl modification on the biological activity of pyrrolo[2,3-d]pyrimidine containing classical and nonclassical antifolates as inhibitors of dihydrofolate reductase and as antitumor and/or antiopportunistic infection agents.Journal of medicinal chemistry, , Aug-14, Volume: 51, Issue:15, 2008
Probing the molecular basis of resistance to pyrimethamine by site-directed mutagenesis.Journal of medicinal chemistry, , Jul-24, Volume: 35, Issue:15, 1992
The hypothetical active site lattice. An approach to modelling active sites from data on inhibitor molecules.Journal of medicinal chemistry, , Volume: 31, Issue:7, 1988
Charged Nonclassical Antifolates with Activity Against Gram-Positive and Gram-Negative Pathogens.ACS medicinal chemistry letters, , Jul-14, Volume: 7, Issue:7, 2016
Novel tricyclic indeno[2,1-d]pyrimidines with dual antiangiogenic and cytotoxic activities as potent antitumor agents.Bioorganic & medicinal chemistry, , Jul-15, Volume: 20, Issue:14, 2012
Single agents with designed combination chemotherapy potential: synthesis and evaluation of substituted pyrimido[4,5-b]indoles as receptor tyrosine kinase and thymidylate synthase inhibitors and as antitumor agents.Journal of medicinal chemistry, , Feb-25, Volume: 53, Issue:4, 2010
Design, synthesis, and X-ray crystal structure of classical and nonclassical 2-amino-4-oxo-5-substituted-6-ethylthieno[2,3-d]pyrimidines as dual thymidylate synthase and dihydrofolate reductase inhibitors and as potential antitumor agents.Journal of medicinal chemistry, , Aug-13, Volume: 52, Issue:15, 2009
Design, synthesis, and biological evaluation of classical and nonclassical 2-amino-4-oxo-5-substituted-6-methylpyrrolo[3,2-d]pyrimidines as dual thymidylate synthase and dihydrofolate reductase inhibitors.Journal of medicinal chemistry, , Jan-10, Volume: 51, Issue:1, 2008
The effect of 5-alkyl modification on the biological activity of pyrrolo[2,3-d]pyrimidine containing classical and nonclassical antifolates as inhibitors of dihydrofolate reductase and as antitumor and/or antiopportunistic infection agents.Journal of medicinal chemistry, , Aug-14, Volume: 51, Issue:15, 2008
Potent dual thymidylate synthase and dihydrofolate reductase inhibitors: classical and nonclassical 2-amino-4-oxo-5-arylthio-substituted-6-methylthieno[2,3-d]pyrimidine antifolates.Journal of medicinal chemistry, , Sep-25, Volume: 51, Issue:18, 2008
Design and synthesis of classical and nonclassical 6-arylthio-2,4-diamino-5-ethylpyrrolo[2,3-d]pyrimidines as antifolates.Journal of medicinal chemistry, , Jun-28, Volume: 50, Issue:13, 2007
Multicopy suppressors for novel antibacterial compounds reveal targets and drug efflux susceptibility.Chemistry & biology, , Volume: 11, Issue:10, 2004
Design, synthesis, and biological activities of classical N-[4-[2-(2-amino-4-ethylpyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-l-glutamic acid and its 6-methyl derivative as potential dual inhibitors of thymidylate synthase and dihydrofolate reductase and Journal of medicinal chemistry, , Feb-13, Volume: 46, Issue:4, 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.Journal of medicinal chemistry, , Nov-06, Volume: 46, Issue:23, 2003
High throughput screening identifies novel inhibitors of Escherichia coli dihydrofolate reductase that are competitive with dihydrofolate.Bioorganic & medicinal chemistry letters, , Aug-04, Volume: 13, Issue:15, 2003
Iclaprim, a novel diaminopyrimidine with potent activity on trimethoprim sensitive and resistant bacteria.Bioorganic & medicinal chemistry letters, , Dec-01, Volume: 13, Issue:23, 2003
Inhibition of Pneumocystis carinii, Toxoplasma gondii, and Mycobacterium avium dihydrofolate reductases by 2,4-diamino-5-[2-methoxy-5-(omega-carboxyalkyloxy)benzyl]pyrimidines: marked improvement in potency relative to trimethoprim and species selectivityJournal of medicinal chemistry, , Jan-03, Volume: 45, Issue:1, 2002
Synthesis of classical and nonclassical, partially restricted, linear, tricyclic 5-deaza antifolates.Journal of medicinal chemistry, , Nov-07, Volume: 45, Issue:23, 2002
Synthesis, antifolate, and antitumor activities of classical and nonclassical 2-amino-4-oxo-5-substituted-pyrrolo[2,3-d]pyrimidines.Journal of medicinal chemistry, , Jun-07, Volume: 44, Issue:12, 2001
Structure-based design and synthesis of lipophilic 2,4-diamino-6-substituted quinazolines and their evaluation as inhibitors of dihydrofolate reductases and potential antitumor agents.Journal of medicinal chemistry, , Aug-27, Volume: 41, Issue:18, 1998
Solution of the conformation and alignment tensors for the binding of trimethoprim and its analogs to dihydrofolate reductase: 3D-quantitative structure-activity relationship study using molecular shape analysis, 3-way partial least-squares regression, anJournal of medicinal chemistry, , Nov-22, Volume: 39, Issue:24, 1996
2,4-Diamino-5-benzylpyrimidines as antibacterial agents. 14. 2,3-Dihydro-1-(2,4-diamino-5-pyrimidyl)-1H-indenes as conformationally restricted analogues of trimethoprim.Journal of medicinal chemistry, , Volume: 34, Issue:2, 1991
Receptor-based design of novel dihydrofolate reductase inhibitors: benzimidazole and indole derivatives.Journal of medicinal chemistry, , Volume: 34, Issue:4, 1991
Antifolate and antibacterial activities of 5-substituted 2,4-diaminoquinazolines.Journal of medicinal chemistry, , Volume: 33, Issue:1, 1990
2,4-Diamino-5-benzylpyrimidines and analogues as antibacterial agents. 11. Quinolylmethyl analogues with basic substituents conveying specificity.Journal of medicinal chemistry, , Volume: 32, Issue:8, 1989
2,4-Diamino-5-benzylpyrimidines and analogues as antibacterial agents. 10. 2,4-Diamino-5-(6-quinolylmethyl)- and -[(tetrahydro-6-quinolyl)methyl]pyrimidine derivatives. Further specificity studies.Journal of medicinal chemistry, , Volume: 32, Issue:8, 1989
2,4-Diamino-5-benzylpyrimidines and analogues as antibacterial agents. 12. 1,2-Dihydroquinolylmethyl analogues with high activity and specificity for bacterial dihydrofolate reductase.Journal of medicinal chemistry, , Volume: 32, Issue:8, 1989
2,4-Diamino-5-benzylpyrimidines as antibacterial agents. 13. Some alkenyl derivatives with high in vitro activity against anaerobic organisms.Journal of medicinal chemistry, , Volume: 32, Issue:8, 1989
The hypothetical active site lattice. An approach to modelling active sites from data on inhibitor molecules.Journal of medicinal chemistry, , Volume: 31, Issue:7, 1988
2,4-Diamino-5-benzylpyrimidines as antibacterial agents. 8. The 3,4,5-triethyl isostere of trimethoprim. A study of specificity.Journal of medicinal chemistry, , Volume: 30, Issue:11, 1987
2,4-Diamino-5-benzylpyrimidines as antibacterial agents. 7. Analysis of the effect of 3,5-dialkyl substituent size and shape on binding to four different dihydrofolate reductase enzymes.Journal of medicinal chemistry, , Volume: 30, Issue:2, 1987
Receptor-based design of dihydrofolate reductase inhibitors: comparison of crystallographically determined enzyme binding with enzyme affinity in a series of carboxy-substituted trimethoprim analogues.Journal of medicinal chemistry, , Volume: 28, Issue:3, 1985
Receptor-based design of dihydrofolate reductase inhibitors: comparison of crystallographically determined enzyme binding with enzyme affinity in a series of carboxy-substituted trimethoprim analogues.Journal of medicinal chemistry, , Volume: 25, Issue:10, 1982
2,4-Diamino-5-benzylpyrimidines and analogues as antibacterial agents. 5. 3',5'-Dimethoxy-4'-substituted-benzyl analogues of trimethoprim.Journal of medicinal chemistry, , Volume: 24, Issue:8, 1981
2,4-Diamino-5-benzylpyrimidines as antibacterial agents. 4. 6-Substituted trimethoprim derivatives from phenolic Mannich intermediates. Application to the synthesis of trimethoprim and 3,5-dialkylbenzyl analogues.Journal of medicinal chemistry, , Volume: 23, Issue:5, 1980
2,4-Diamino-5-benzylpyrimidines and analogues as antibacterial agents. 2. C-Alkylation of pyrimidines with Mannich bases and application to the synthesis of trimethoprim and analogues.Journal of medicinal chemistry, , Volume: 23, Issue:4, 1980
Design and synthesis of classical and nonclassical 6-arylthio-2,4-diamino-5-ethylpyrrolo[2,3-d]pyrimidines as antifolates.Journal of medicinal chemistry, , Jun-28, Volume: 50, Issue:13, 2007
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.Journal of medicinal chemistry, , Nov-06, Volume: 46, Issue:23, 2003
Synthesis of classical and nonclassical, partially restricted, linear, tricyclic 5-deaza antifolates.Journal of medicinal chemistry, , Nov-07, Volume: 45, Issue:23, 2002
Synthesis, antifolate, and antitumor activities of classical and nonclassical 2-amino-4-oxo-5-substituted-pyrrolo[2,3-d]pyrimidines.Journal of medicinal chemistry, , Jun-07, Volume: 44, Issue:12, 2001
Structure-based design and synthesis of lipophilic 2,4-diamino-6-substituted quinazolines and their evaluation as inhibitors of dihydrofolate reductases and potential antitumor agents.Journal of medicinal chemistry, , Aug-27, Volume: 41, Issue:18, 1998
2,4-Diaminothieno[2,3-d]pyrimidine analogues of trimetrexate and piritrexim as potential inhibitors of Pneumocystis carinii and Toxoplasma gondii dihydrofolate reductase.Journal of medicinal chemistry, , Oct-15, Volume: 36, Issue:21, 1993
Quantitative structure-activity relationships of the inhibition of Pneumocystis carinii dihydrofolate reductase by 4,6-diamino-1,2-dihydro-2,2-dimethyl-1-(X-phenyl)-s-triazines.Journal of medicinal chemistry, , Mar-17, Volume: 38, Issue:6, 1995
The hypothetical active site lattice. An approach to modelling active sites from data on inhibitor molecules.Journal of medicinal chemistry, , Volume: 31, Issue:7, 1988
2,4-Diamino-5-benzylpyrimidines as antibacterial agents. 14. 2,3-Dihydro-1-(2,4-diamino-5-pyrimidyl)-1H-indenes as conformationally restricted analogues of trimethoprim.Journal of medicinal chemistry, , Volume: 34, Issue:2, 1991
The hypothetical active site lattice. An approach to modelling active sites from data on inhibitor molecules.Journal of medicinal chemistry, , Volume: 31, Issue:7, 1988
2,4-Diamino-5-benzylpyrimidines as antibacterial agents. 8. The 3,4,5-triethyl isostere of trimethoprim. A study of specificity.Journal of medicinal chemistry, , Volume: 30, Issue:11, 1987
2,4-Diamino-5-benzylpyrimidines as antibacterial agents. 7. Analysis of the effect of 3,5-dialkyl substituent size and shape on binding to four different dihydrofolate reductase enzymes.Journal of medicinal chemistry, , Volume: 30, Issue:2, 1987
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.Journal of medicinal chemistry, , Nov-06, Volume: 46, Issue:23, 2003
Inhibition of Pneumocystis carinii, Toxoplasma gondii, and Mycobacterium avium dihydrofolate reductases by 2,4-diamino-5-[2-methoxy-5-(omega-carboxyalkyloxy)benzyl]pyrimidines: marked improvement in potency relative to trimethoprim and species selectivityJournal of medicinal chemistry, , Jan-03, Volume: 45, Issue:1, 2002
2,4-Diaminothieno[2,3-d]pyrimidine analogues of trimetrexate and piritrexim as potential inhibitors of Pneumocystis carinii and Toxoplasma gondii dihydrofolate reductase.Journal of medicinal chemistry, , Oct-15, Volume: 36, Issue:21, 1993
The hypothetical active site lattice. An approach to modelling active sites from data on inhibitor molecules.Journal of medicinal chemistry, , Volume: 31, Issue:7, 1988
2,4-Diamino-5-benzylpyrimidines and analogues as antibacterial agents. 5. 3',5'-Dimethoxy-4'-substituted-benzyl analogues of trimethoprim.Journal of medicinal chemistry, , Volume: 24, Issue:8, 1981
Solution of the conformation and alignment tensors for the binding of trimethoprim and its analogs to dihydrofolate reductase: 3D-quantitative structure-activity relationship study using molecular shape analysis, 3-way partial least-squares regression, anJournal of medicinal chemistry, , Nov-22, Volume: 39, Issue:24, 1996
The hypothetical active site lattice. An approach to modelling active sites from data on inhibitor molecules.Journal of medicinal chemistry, , Volume: 31, Issue:7, 1988
Solution of the conformation and alignment tensors for the binding of trimethoprim and its analogs to dihydrofolate reductase: 3D-quantitative structure-activity relationship study using molecular shape analysis, 3-way partial least-squares regression, anJournal of medicinal chemistry, , Nov-22, Volume: 39, Issue:24, 1996
The hypothetical active site lattice. An approach to modelling active sites from data on inhibitor molecules.Journal of medicinal chemistry, , Volume: 31, Issue:7, 1988
Quantitative structure-activity relationships of antimalarial and dihydrofolate reductase inhibition by quinazolines and 5-substituted benzyl-2,4-diaminopyrimidines.Journal of medicinal chemistry, , Volume: 20, Issue:1, 1977
Charged Nonclassical Antifolates with Activity Against Gram-Positive and Gram-Negative Pathogens.ACS medicinal chemistry letters, , Jul-14, Volume: 7, Issue:7, 2016
Novel tricyclic indeno[2,1-d]pyrimidines with dual antiangiogenic and cytotoxic activities as potent antitumor agents.Bioorganic & medicinal chemistry, , Jul-15, Volume: 20, Issue:14, 2012
Design, synthesis, biological evaluation and X-ray crystal structure of novel classical 6,5,6-tricyclic benzo[4,5]thieno[2,3-d]pyrimidines as dual thymidylate synthase and dihydrofolate reductase inhibitors.Bioorganic & medicinal chemistry, , Jun-01, Volume: 19, Issue:11, 2011
Single agents with designed combination chemotherapy potential: synthesis and evaluation of substituted pyrimido[4,5-b]indoles as receptor tyrosine kinase and thymidylate synthase inhibitors and as antitumor agents.Journal of medicinal chemistry, , Feb-25, Volume: 53, Issue:4, 2010
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 & medicinal chemistry, , Jan-15, Volume: 18, Issue:2, 2010
Design, synthesis, and X-ray crystal structure of classical and nonclassical 2-amino-4-oxo-5-substituted-6-ethylthieno[2,3-d]pyrimidines as dual thymidylate synthase and dihydrofolate reductase inhibitors and as potential antitumor agents.Journal of medicinal chemistry, , Aug-13, Volume: 52, Issue:15, 2009
Design, synthesis, and biological evaluation of classical and nonclassical 2-amino-4-oxo-5-substituted-6-methylpyrrolo[3,2-d]pyrimidines as dual thymidylate synthase and dihydrofolate reductase inhibitors.Journal of medicinal chemistry, , Jan-10, Volume: 51, Issue:1, 2008
The effect of 5-alkyl modification on the biological activity of pyrrolo[2,3-d]pyrimidine containing classical and nonclassical antifolates as inhibitors of dihydrofolate reductase and as antitumor and/or antiopportunistic infection agents.Journal of medicinal chemistry, , Aug-14, Volume: 51, Issue:15, 2008
Potent dual thymidylate synthase and dihydrofolate reductase inhibitors: classical and nonclassical 2-amino-4-oxo-5-arylthio-substituted-6-methylthieno[2,3-d]pyrimidine antifolates.Journal of medicinal chemistry, , Sep-25, Volume: 51, Issue:18, 2008
Design and synthesis of classical and nonclassical 6-arylthio-2,4-diamino-5-ethylpyrrolo[2,3-d]pyrimidines as antifolates.Journal of medicinal chemistry, , Jun-28, Volume: 50, Issue:13, 2007
A 2.13 A structure of E. coli dihydrofolate reductase bound to a novel competitive inhibitor reveals a new binding surface involving the M20 loop region.Journal of medicinal chemistry, , Nov-30, Volume: 49, Issue:24, 2006
MASPIT: three-hybrid trap for quantitative proteome fingerprinting of small molecule-protein interactions in mammalian cells.Chemistry & biology, , Volume: 13, Issue:7, 2006
Synthesis of classical, four-carbon bridged 5-substituted furo[2,3-d]pyrimidine and 6-substituted pyrrolo[2,3-d]pyrimidine analogues as antifolates.Journal of medicinal chemistry, , Aug-11, Volume: 48, Issue:16, 2005
Synthesis of N-{4-[(2,4-diamino-5-methyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)thio]benzoyl}-L-glutamic acid and N-{4-[(2-amino-4-oxo-5-methyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)thio]benzoyl}-L-glutamic acid as dual inhibitors of dihydrofolJournal of medicinal chemistry, , Nov-17, Volume: 48, Issue:23, 2005
Tight binding ligand approach to oligosaccharide-grafted protein.Bioorganic & medicinal chemistry letters, , May-03, Volume: 14, Issue:9, 2004
Synthesis of classical, three-carbon-bridged 5-substituted furo[2,3-d]pyrimidine and 6-substituted pyrrolo[2,3-d]pyrimidine analogues as antifolates.Journal of medicinal chemistry, , Dec-30, Volume: 47, Issue:27, 2004
Benzoyl ring halogenated classical 2-amino-6-methyl-3,4-dihydro-4-oxo-5-substituted thiobenzoyl-7H-pyrrolo[2,3-d]pyrimidine antifolates as inhibitors of thymidylate synthase and as antitumor agents.Journal of medicinal chemistry, , Dec-30, Volume: 47, Issue:27, 2004
Design, synthesis, and biological activities of classical N-[4-[2-(2-amino-4-ethylpyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-l-glutamic acid and its 6-methyl derivative as potential dual inhibitors of thymidylate synthase and dihydrofolate reductase and Journal of medicinal chemistry, , Feb-13, Volume: 46, Issue:4, 2003
Synthesis of N-[4-[1-ethyl-2-(2,4-diaminofuro[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic acid as an antifolate.Journal of medicinal chemistry, , Apr-25, Volume: 45, Issue:9, 2002
Synthesis of classical and nonclassical, partially restricted, linear, tricyclic 5-deaza antifolates.Journal of medicinal chemistry, , Nov-07, Volume: 45, Issue:23, 2002
Synthesis, antifolate, and antitumor activities of classical and nonclassical 2-amino-4-oxo-5-substituted-pyrrolo[2,3-d]pyrimidines.Journal of medicinal chemistry, , Jun-07, Volume: 44, Issue:12, 2001
Effect of C9-methyl substitution and C8-C9 conformational restriction on antifolate and antitumor activity of classical 5-substituted 2,4-diaminofuro[2,3-d]pyrimidines.Journal of medicinal chemistry, , Aug-10, Volume: 43, Issue:16, 2000
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, , Oct-19, Volume: 43, Issue:21, 2000
2,4-diamino-5-deaza-6-substituted pyrido[2,3-d]pyrimidine antifolates as potent and selective nonclassical inhibitors of dihydrofolate reductases.Journal of medicinal chemistry, , Mar-29, Volume: 39, Issue:7, 1996
Evaluation of the importance of hydrophobic interactions in drug binding to dihydrofolate reductase.Journal of medicinal chemistry, , Volume: 31, Issue:1, 1988
Receptor-based design of dihydrofolate reductase inhibitors: comparison of crystallographically determined enzyme binding with enzyme affinity in a series of carboxy-substituted trimethoprim analogues.Journal of medicinal chemistry, , Volume: 28, Issue:3, 1985
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 & medicinal chemistry, , Jan-15, Volume: 18, Issue:2, 2010
Synthesis of N-{4-[(2,4-diamino-5-methyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)thio]benzoyl}-L-glutamic acid and N-{4-[(2-amino-4-oxo-5-methyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)thio]benzoyl}-L-glutamic acid as dual inhibitors of dihydrofolJournal of medicinal chemistry, , Nov-17, Volume: 48, Issue:23, 2005
Potent dual thymidylate synthase and dihydrofolate reductase inhibitors: classical and nonclassical 2-amino-4-oxo-5-arylthio-substituted-6-methylthieno[2,3-d]pyrimidine antifolates.Journal of medicinal chemistry, , Sep-25, Volume: 51, Issue:18, 2008
Synthesis of N-{4-[(2,4-diamino-5-methyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)thio]benzoyl}-L-glutamic acid and N-{4-[(2-amino-4-oxo-5-methyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)thio]benzoyl}-L-glutamic acid as dual inhibitors of dihydrofolJournal of medicinal chemistry, , Nov-17, Volume: 48, Issue:23, 2005
Design, synthesis, biological evaluation and X-ray crystal structure of novel classical 6,5,6-tricyclic benzo[4,5]thieno[2,3-d]pyrimidines as dual thymidylate synthase and dihydrofolate reductase inhibitors.Bioorganic & medicinal chemistry, , Jun-01, Volume: 19, Issue:11, 2011
Design, synthesis, biological evaluation and X-ray crystal structure of novel classical 6,5,6-tricyclic benzo[4,5]thieno[2,3-d]pyrimidines as dual thymidylate synthase and dihydrofolate reductase inhibitors.Bioorganic & medicinal chemistry, , Jun-01, Volume: 19, Issue:11, 2011
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 & medicinal chemistry, , Jan-15, Volume: 18, Issue:2, 2010
Design, synthesis, and X-ray crystal structure of classical and nonclassical 2-amino-4-oxo-5-substituted-6-ethylthieno[2,3-d]pyrimidines as dual thymidylate synthase and dihydrofolate reductase inhibitors and as potential antitumor agents.Journal of medicinal chemistry, , Aug-13, Volume: 52, Issue:15, 2009
The effect of 5-alkyl modification on the biological activity of pyrrolo[2,3-d]pyrimidine containing classical and nonclassical antifolates as inhibitors of dihydrofolate reductase and as antitumor and/or antiopportunistic infection agents.Journal of medicinal chemistry, , Aug-14, Volume: 51, Issue:15, 2008
Potent dual thymidylate synthase and dihydrofolate reductase inhibitors: classical and nonclassical 2-amino-4-oxo-5-arylthio-substituted-6-methylthieno[2,3-d]pyrimidine antifolates.Journal of medicinal chemistry, , Sep-25, Volume: 51, Issue:18, 2008
Synthesis of N-{4-[(2,4-diamino-5-methyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)thio]benzoyl}-L-glutamic acid and N-{4-[(2-amino-4-oxo-5-methyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)thio]benzoyl}-L-glutamic acid as dual inhibitors of dihydrofolJournal of medicinal chemistry, , Nov-17, Volume: 48, Issue:23, 2005
Synthesis of classical, four-carbon bridged 5-substituted furo[2,3-d]pyrimidine and 6-substituted pyrrolo[2,3-d]pyrimidine analogues as antifolates.Journal of medicinal chemistry, , Aug-11, Volume: 48, Issue:16, 2005
Synthesis of classical, three-carbon-bridged 5-substituted furo[2,3-d]pyrimidine and 6-substituted pyrrolo[2,3-d]pyrimidine analogues as antifolates.Journal of medicinal chemistry, , Dec-30, Volume: 47, Issue:27, 2004
Benzoyl ring halogenated classical 2-amino-6-methyl-3,4-dihydro-4-oxo-5-substituted thiobenzoyl-7H-pyrrolo[2,3-d]pyrimidine antifolates as inhibitors of thymidylate synthase and as antitumor agents.Journal of medicinal chemistry, , Dec-30, Volume: 47, Issue:27, 2004
Design, synthesis, and biological activities of classical N-[4-[2-(2-amino-4-ethylpyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-l-glutamic acid and its 6-methyl derivative as potential dual inhibitors of thymidylate synthase and dihydrofolate reductase and Journal of medicinal chemistry, , Feb-13, Volume: 46, Issue:4, 2003
Synthesis, antifolate, and antitumor activities of classical and nonclassical 2-amino-4-oxo-5-substituted-pyrrolo[2,3-d]pyrimidines.Journal of medicinal chemistry, , Jun-07, Volume: 44, Issue:12, 2001
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, , Oct-19, Volume: 43, Issue:21, 2000
Design, synthesis, biological evaluation and X-ray crystal structure of novel classical 6,5,6-tricyclic benzo[4,5]thieno[2,3-d]pyrimidines as dual thymidylate synthase and dihydrofolate reductase inhibitors.Bioorganic & medicinal chemistry, , Jun-01, Volume: 19, Issue:11, 2011
Design, synthesis, and X-ray crystal structure of classical and nonclassical 2-amino-4-oxo-5-substituted-6-ethylthieno[2,3-d]pyrimidines as dual thymidylate synthase and dihydrofolate reductase inhibitors and as potential antitumor agents.Journal of medicinal chemistry, , Aug-13, Volume: 52, Issue:15, 2009
Design, synthesis, and biological evaluation of classical and nonclassical 2-amino-4-oxo-5-substituted-6-methylpyrrolo[3,2-d]pyrimidines as dual thymidylate synthase and dihydrofolate reductase inhibitors.Journal of medicinal chemistry, , Jan-10, Volume: 51, Issue:1, 2008
Synthesis of N-{4-[(2,4-diamino-5-methyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)thio]benzoyl}-L-glutamic acid and N-{4-[(2-amino-4-oxo-5-methyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)thio]benzoyl}-L-glutamic acid as dual inhibitors of dihydrofolJournal of medicinal chemistry, , Nov-17, Volume: 48, Issue:23, 2005