Page last updated: 2024-08-07 15:30:14
Dihydrofolate reductase
A dihydrofolate reductase that is encoded in the genome of human. [PRO:DAN, UniProtKB:P00374]
Synonyms
EC 1.5.1.3
Research
Bioassay Publications (126)
| Timeframe | Studies on this Protein(%) | All Drugs % |
|---|
| pre-1990 | 14 (11.11) | 18.7374 |
| 1990's | 24 (19.05) | 18.2507 |
| 2000's | 38 (30.16) | 29.6817 |
| 2010's | 41 (32.54) | 24.3611 |
| 2020's | 9 (7.14) | 2.80 |
Compounds (55)
Drugs with Inhibition Measurements
| Drug | Taxonomy | Measurement | Average (mM) | Bioassay(s) | Publication(s) |
|---|
| hippuric acid | Homo sapiens (human) | Ki | 17,000.0000 | 1 | 1 |
| ag 1295 | Homo sapiens (human) | IC50 | 6.2000 | 1 | 1 |
| diclofenac | Homo sapiens (human) | Ki | 160.0000 | 1 | 1 |
| diflunisal | Homo sapiens (human) | Ki | 34.0000 | 1 | 1 |
| etodolac | Homo sapiens (human) | Ki | 1,800.0000 | 1 | 1 |
| fenbufen | Homo sapiens (human) | Ki | 360.0000 | 1 | 1 |
| ibuprofen | Homo sapiens (human) | Ki | 560.0000 | 1 | 1 |
| mefenamic acid | Homo sapiens (human) | Ki | 72.0000 | 1 | 1 |
| metformin | Homo sapiens (human) | Ki | 18,000.0000 | 1 | 1 |
| doxorubicin hydrochloride | Homo sapiens (human) | IC50 | 0.0300 | 1 | 1 |
| pd 153035 | Homo sapiens (human) | IC50 | 0.2000 | 1 | 1 |
| pyrimethamine | Homo sapiens (human) | IC50 | 3.1057 | 7 | 7 |
| pyrimethamine | Homo sapiens (human) | Ki | 0.1160 | 9 | 9 |
| riluzole | Homo sapiens (human) | IC50 | 312.0000 | 1 | 1 |
| sulfacetamide | Homo sapiens (human) | IC50 | 18.0000 | 1 | 1 |
| trimethoprim | Homo sapiens (human) | IC50 | 205.3070 | 44 | 62 |
| trimethoprim | Homo sapiens (human) | Ki | 11.6282 | 12 | 12 |
| trimetrexate | Homo sapiens (human) | IC50 | 24.3049 | 11 | 14 |
| trimetrexate | Homo sapiens (human) | Ki | 0.0244 | 4 | 4 |
| tryptophan | Homo sapiens (human) | IC50 | 6,500.0000 | 1 | 1 |
| tryptophan | Homo sapiens (human) | Ki | 2,800.0000 | 1 | 1 |
| phenformin | Homo sapiens (human) | Ki | 140.0000 | 1 | 1 |
| cycloguanil | Homo sapiens (human) | Ki | 14.4885 | 3 | 3 |
| D-tryptophan | Homo sapiens (human) | Ki | 880.0000 | 1 | 1 |
| 4,6-diamino-2,2-dimethyl-1,2-dihydro-1-phenyl-s-triazine | Homo sapiens (human) | Ki | 1.6596 | 1 | 1 |
| diaveridine | Homo sapiens (human) | IC50 | 0.5300 | 1 | 1 |
| piritrexim | Homo sapiens (human) | IC50 | 0.0024 | 5 | 5 |
| piritrexim | Homo sapiens (human) | Ki | 0.0237 | 3 | 3 |
| brequinar | Homo sapiens (human) | IC50 | 0.0018 | 1 | 1 |
| 2,4-diaminopyrimidine | Homo sapiens (human) | Ki | 180.0000 | 1 | 1 |
| epiroprim | Homo sapiens (human) | IC50 | 300.1000 | 2 | 2 |
| epiroprim | Homo sapiens (human) | Ki | 0.0589 | 1 | 1 |
| sori 8895 | Homo sapiens (human) | IC50 | 1.0000 | 1 | 1 |
| sori 8890 | Homo sapiens (human) | IC50 | 0.0150 | 1 | 1 |
| 10-deazaaminopterin | Homo sapiens (human) | IC50 | 0.0041 | 1 | 1 |
| wr 99210 | Homo sapiens (human) | Ki | 7.3038 | 2 | 2 |
| methotrexate | Homo sapiens (human) | IC50 | 1.5079 | 80 | 94 |
| methotrexate | Homo sapiens (human) | Ki | 0.4019 | 11 | 11 |
| 10-propargyl-10-deazaaminopterin | Homo sapiens (human) | Ki | 0.0000 | 1 | 1 |
| naproxen | Homo sapiens (human) | Ki | 7,000.0000 | 1 | 1 |
| n-(4-(n-((2,4-diaminofuro(2,3-d)pyrimidin-5-yl)methyl)amino)benzoyl)glutamic acid | Homo sapiens (human) | IC50 | 0.3925 | 4 | 4 |
| aminopterin | Homo sapiens (human) | IC50 | 0.0201 | 6 | 6 |
| aminopterin | Homo sapiens (human) | Ki | 0.0001 | 3 | 3 |
| 4-aminobenzoylglutamic acid | Homo sapiens (human) | Ki | 180.0000 | 1 | 1 |
| iclaprim | Homo sapiens (human) | IC50 | 47.4900 | 3 | 7 |
| iclaprim | Homo sapiens (human) | Ki | 0.7750 | 2 | 2 |
| chalcone | Homo sapiens (human) | IC50 | 100.0000 | 1 | 1 |
| flavin mononucleotide | Homo sapiens (human) | IC50 | 325.0000 | 1 | 1 |
| 1-methyltryptophan | Homo sapiens (human) | Ki | 810.0000 | 1 | 1 |
| semaxinib | Homo sapiens (human) | IC50 | 2.4000 | 1 | 1 |
| edatrexate | Homo sapiens (human) | IC50 | 0.0035 | 2 | 2 |
| gentamicin sulfate | Homo sapiens (human) | IC50 | 18.0000 | 1 | 1 |
| teriflunomide | Homo sapiens (human) | IC50 | 0.3880 | 1 | 1 |
| raltitrexed | Homo sapiens (human) | IC50 | 10.5877 | 4 | 9 |
| n-(4(n-((2-amino-4-hydroxy-6-quinazolinyl)methyl)prop-2-ynylamino)benzoyl)-l-glutamic acid | Homo sapiens (human) | IC50 | 5.0171 | 7 | 7 |
| leucovorin | Homo sapiens (human) | Ki | 2.3700 | 1 | 1 |
| 1843u89 | Homo sapiens (human) | IC50 | 20.0000 | 1 | 1 |
| 5,11-methenyltetrahydrohomofolate | Homo sapiens (human) | IC50 | 100.0000 | 1 | 1 |
| pemetrexed | Homo sapiens (human) | IC50 | 7.6762 | 17 | 17 |
| pemetrexed | Homo sapiens (human) | Ki | 0.0071 | 3 | 3 |
| cb 3717 | Homo sapiens (human) | IC50 | 4.3532 | 6 | 21 |
| cb 3717 | Homo sapiens (human) | Ki | 0.0500 | 1 | 3 |
| (5)n,(8)n-deaza-(10)-n-methylfolate | Homo sapiens (human) | IC50 | 0.0830 | 1 | 1 |
Drugs with Other Measurements
Discovery of Selective Toxoplasma gondii Dihydrofolate Reductase Inhibitors for the Treatment of Toxoplasmosis.Journal of medicinal chemistry, , 02-14, Volume: 62, Issue:3, 2019
6-Hydrophobic aromatic substituent pyrimethamine analogues as potential antimalarials for pyrimethamine-resistant Plasmodium falciparum.Bioorganic & medicinal chemistry, , 12-15, Volume: 27, Issue:24, 2019
Hybrid Inhibitors of Malarial Dihydrofolate Reductase with Dual Binding Modes That Can Forestall Resistance.ACS medicinal chemistry letters, , Dec-13, Volume: 9, Issue:12, 2018
Host dihydrofolate reductase (DHFR)-directed cycloguanil analogues endowed with activity against influenza virus and respiratory syncytial virus.European journal of medicinal chemistry, , Jul-28, Volume: 135, 2017
Discovery of Potent and Selective Leads against ACS medicinal chemistry letters, , Dec-08, Volume: 7, Issue:12, 2016
Design, synthesis, and molecular modeling of novel pyrido[2,3-d]pyrimidine analogues as antifolates; application of Buchwald-Hartwig aminations of heterocycles.Journal of medicinal chemistry, , Jun-13, Volume: 56, Issue:11, 2013
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
Preclinical evaluation of the antifolate QN254, 5-chloro- N'6'-(2,5-dimethoxy-benzyl)-quinazoline-2,4,6-triamine, as an antimalarial drug candidate.Antimicrobial agents and chemotherapy, , Volume: 54, Issue:6, 2010
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
Development of 2,4-diaminopyrimidines as antimalarials based on inhibition of the S108N and C59R+S108N mutants of dihydrofolate reductase from pyrimethamine-resistant Plasmodium falciparum.Journal of medicinal chemistry, , Mar-14, Volume: 45, Issue:6, 2002
Design, synthesis, and evaluation of inhibitors of trypanosomal and leishmanial dihydrofolate reductase.Journal of medicinal chemistry, , Oct-21, Volume: 42, Issue:21, 1999
Selective inhibitors of Candida albicans dihydrofolate reductase: activity and selectivity of 5-(arylthio)-2,4-diaminoquinazolines.Journal of medicinal chemistry, , Sep-01, Volume: 38, Issue:18, 1995
Exploring the ability of dihydropyrimidine-5-carboxamide and 5-benzyl-2,4-diaminopyrimidine-based analogues for the selective inhibition of L. major dihydrofolate reductase.European journal of medicinal chemistry, , Jan-15, Volume: 210, 2021
Discovery of Selective Toxoplasma gondii Dihydrofolate Reductase Inhibitors for the Treatment of Toxoplasmosis.Journal of medicinal chemistry, , 02-14, Volume: 62, Issue:3, 2019
Development of substituted pyrido[3,2-d]pyrimidines as potent and selective dihydrofolate reductase inhibitors for pneumocystis pneumonia infection.Bioorganic & medicinal chemistry letters, , 08-01, Volume: 29, Issue:15, 2019
Targeting species specific amino acid residues: Design, synthesis and biological evaluation of 6-substituted pyrrolo[2,3-d]pyrimidines as dihydrofolate reductase inhibitors and potential anti-opportunistic infection agents.Bioorganic & medicinal chemistry, , 05-15, Volume: 26, Issue:9, 2018
Synthesis and evaluation of 5-(arylthio)-9H-pyrimido[4,5-b]indole-2,4-diamines as receptor tyrosine kinase and thymidylate synthase inhibitors and as antitumor agents.Bioorganic & medicinal chemistry letters, , 04-01, Volume: 27, Issue:7, 2017
Host dihydrofolate reductase (DHFR)-directed cycloguanil analogues endowed with activity against influenza virus and respiratory syncytial virus.European journal of medicinal chemistry, , Jul-28, Volume: 135, 2017
Charged Nonclassical Antifolates with Activity Against Gram-Positive and Gram-Negative Pathogens.ACS medicinal chemistry letters, , Jul-14, Volume: 7, Issue:7, 2016
Elements and modulation of functional dynamics.Journal of medicinal chemistry, , Oct-09, Volume: 57, Issue:19, 2014
Structure-based design of new dihydrofolate reductase antibacterial agents: 7-(benzimidazol-1-yl)-2,4-diaminoquinazolines.Journal of medicinal chemistry, , Feb-13, Volume: 57, Issue:3, 2014
Design, synthesis, and molecular modeling of novel pyrido[2,3-d]pyrimidine analogues as antifolates; application of Buchwald-Hartwig aminations of heterocycles.Journal of medicinal chemistry, , Jun-13, Volume: 56, Issue:11, 2013
Structure aided design of chimeric antibiotics.Bioorganic & medicinal chemistry letters, , Apr-01, Volume: 22, Issue:7, 2012
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
Structure-based design of new DHFR-based antibacterial agents: 7-aryl-2,4-diaminoquinazolines.Bioorganic & medicinal chemistry letters, , Sep-15, Volume: 21, Issue:18, 2011
Synthesis and antimicrobial activity of N¹-benzyl or N¹-benzyloxy-1,6-dihydro-1,3,5-triazine-2,4-diamines.Bioorganic & medicinal chemistry letters, , Sep-15, Volume: 21, Issue:18, 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
Design, synthesis, and X-ray crystal structures of 2,4-diaminofuro[2,3-d]pyrimidines as multireceptor tyrosine kinase and dihydrofolate reductase inhibitors.Bioorganic & medicinal chemistry, , Oct-15, Volume: 17, Issue:20, 2009
In vitro biological activity and structural analysis of 2,4-diamino-5-(2'-arylpropargyl)pyrimidine inhibitors of Candida albicans.Bioorganic & medicinal chemistry, , Jul-15, Volume: 17, Issue:14, 2009
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
Structure-guided development of efficacious antifungal agents targeting Candida glabrata dihydrofolate reductase.Chemistry & biology, , Sep-22, Volume: 15, Issue:9, 2008
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
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
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
Synthetic and crystallographic studies of a new inhibitor series targeting Bacillus anthracis dihydrofolate reductase.Journal of medicinal chemistry, , Dec-11, Volume: 51, Issue:23, 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
Functional cloning of Bacillus anthracis dihydrofolate reductase and confirmation of natural resistance to trimethoprim.Antimicrobial agents and chemotherapy, , Volume: 48, Issue:12, 2004
Synthesis of 2,4-diamino-6-[2'-O-(omega-carboxyalkyl)oxydibenz[b,f]azepin-5-yl]methylpteridines as potent and selective inhibitors of Pneumocystis carinii, Toxoplasma gondii, and Mycobacterium avium dihydrofolate reductase.Journal of medicinal chemistry, , May-06, Volume: 47, Issue:10, 2004
New 2,4-diamino-5-(2',5'-substituted benzyl)pyrimidines as potential drugs against opportunistic infections of AIDS and other immune disorders. Synthesis and species-dependent antifolate activity.Journal of medicinal chemistry, , Mar-11, Volume: 47, Issue:6, 2004
Iclaprim, a novel diaminopyrimidine with potent activity on trimethoprim sensitive and resistant bacteria.Bioorganic & medicinal chemistry letters, , Dec-01, Volume: 13, Issue:23, 2003
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
Novel dihydrofolate reductase inhibitors. Structure-based versus diversity-based library design and high-throughput synthesis and screening.Journal of medicinal chemistry, , Jun-05, Volume: 46, Issue:12, 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
Design, synthesis, and evaluation of inhibitors of trypanosomal and leishmanial dihydrofolate reductase.Journal of medicinal chemistry, , Oct-21, Volume: 42, Issue:21, 1999
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
Selective inhibitors of Candida albicans dihydrofolate reductase: activity and selectivity of 5-(arylthio)-2,4-diaminoquinazolines.Journal of medicinal chemistry, , Sep-01, Volume: 38, Issue:18, 1995
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
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 as antibacterial agents. 13. Some alkenyl derivatives with high in vitro activity against anaerobic organisms.Journal of medicinal chemistry, , Volume: 32, Issue:8, 1989
2,4-Diamino-5-benzylpyrimidines and analogues as antibacterial agents. 9. Lipophilic trimethoprim analogues as antigonococcal agents.Journal of medicinal chemistry, , Volume: 31, Issue:1, 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
Therapeutic progression of quinazolines as targeted chemotherapeutic agents.European journal of medicinal chemistry, , Feb-05, Volume: 211, 2021
Discovery of Selective Toxoplasma gondii Dihydrofolate Reductase Inhibitors for the Treatment of Toxoplasmosis.Journal of medicinal chemistry, , 02-14, Volume: 62, Issue:3, 2019
Development of substituted pyrido[3,2-d]pyrimidines as potent and selective dihydrofolate reductase inhibitors for pneumocystis pneumonia infection.Bioorganic & medicinal chemistry letters, , 08-01, Volume: 29, Issue:15, 2019
Design, synthesis, and molecular modeling of novel pyrido[2,3-d]pyrimidine analogues as antifolates; application of Buchwald-Hartwig aminations of heterocycles.Journal of medicinal chemistry, , Jun-13, Volume: 56, Issue:11, 2013
Synthesis and characterization of potent inhibitors of Trypanosoma cruzi dihydrofolate reductase.Bioorganic & medicinal chemistry, , Jun-01, Volume: 18, Issue:11, 2010
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 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
High-affinity inhibitors of dihydrofolate reductase: antimicrobial and anticancer activities of 7,8-dialkyl-1,3-diaminopyrrolo[3,2-f]quinazolines with small molecular size.Journal of medicinal chemistry, , Feb-16, Volume: 39, Issue:4, 1996
Selective inhibitors of Candida albicans dihydrofolate reductase: activity and selectivity of 5-(arylthio)-2,4-diaminoquinazolines.Journal of medicinal chemistry, , Sep-01, Volume: 38, Issue:18, 1995
2,4-Diamino-5-substituted-quinazolines as inhibitors of a human dihydrofolate reductase with a site-directed mutation at position 22 and of the dihydrofolate reductases from Pneumocystis carinii and Toxoplasma gondii.Journal of medicinal chemistry, , Mar-03, Volume: 38, Issue:5, 1995
Synthesis and biological activity of N omega-hemiphthaloyl-alpha,omega- diaminoalkanoic acid analogues of aminopterin and 3',5-dichloroaminopterin.Journal of medicinal chemistry, , Jul-08, Volume: 37, Issue:14, 1994
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
Host dihydrofolate reductase (DHFR)-directed cycloguanil analogues endowed with activity against influenza virus and respiratory syncytial virus.European journal of medicinal chemistry, , Jul-28, Volume: 135, 2017
Preclinical evaluation of the antifolate QN254, 5-chloro- N'6'-(2,5-dimethoxy-benzyl)-quinazoline-2,4,6-triamine, as an antimalarial drug candidate.Antimicrobial agents and chemotherapy, , Volume: 54, Issue:6, 2010
Development of substituted pyrido[3,2-d]pyrimidines as potent and selective dihydrofolate reductase inhibitors for pneumocystis pneumonia infection.Bioorganic & medicinal chemistry letters, , 08-01, Volume: 29, Issue:15, 2019
Targeting species specific amino acid residues: Design, synthesis and biological evaluation of 6-substituted pyrrolo[2,3-d]pyrimidines as dihydrofolate reductase inhibitors and potential anti-opportunistic infection agents.Bioorganic & medicinal chemistry, , 05-15, Volume: 26, Issue:9, 2018
Design, synthesis, and molecular modeling of novel pyrido[2,3-d]pyrimidine analogues as antifolates; application of Buchwald-Hartwig aminations of heterocycles.Journal of medicinal chemistry, , Jun-13, Volume: 56, Issue:11, 2013
High-affinity inhibitors of dihydrofolate reductase: antimicrobial and anticancer activities of 7,8-dialkyl-1,3-diaminopyrrolo[3,2-f]quinazolines with small molecular size.Journal of medicinal chemistry, , Feb-16, Volume: 39, Issue:4, 1996
Selective inhibitors of Candida albicans dihydrofolate reductase: activity and selectivity of 5-(arylthio)-2,4-diaminoquinazolines.Journal of medicinal chemistry, , Sep-01, Volume: 38, Issue:18, 1995
2,4-Diamino-5-substituted-quinazolines as inhibitors of a human dihydrofolate reductase with a site-directed mutation at position 22 and of the dihydrofolate reductases from Pneumocystis carinii and Toxoplasma gondii.Journal of medicinal chemistry, , Mar-03, Volume: 38, Issue:5, 1995
Synthesis of 2,4-diamino-6-[2'-O-(omega-carboxyalkyl)oxydibenz[b,f]azepin-5-yl]methylpteridines as potent and selective inhibitors of Pneumocystis carinii, Toxoplasma gondii, and Mycobacterium avium dihydrofolate reductase.Journal of medicinal chemistry, , May-06, Volume: 47, Issue:10, 2004
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
Flexible diaminodihydrotriazine inhibitors of Plasmodium falciparum dihydrofolate reductase: Binding strengths, modes of binding and their antimalarial activities.European journal of medicinal chemistry, , Jun-01, Volume: 195, 2020
Preclinical evaluation of the antifolate QN254, 5-chloro- N'6'-(2,5-dimethoxy-benzyl)-quinazoline-2,4,6-triamine, as an antimalarial drug candidate.Antimicrobial agents and chemotherapy, , Volume: 54, Issue:6, 2010
New thiazole-based derivatives as EGFR/HER2 and DHFR inhibitors: Synthesis, molecular modeling simulations and anticancer activity.European journal of medicinal chemistry, , Nov-05, Volume: 241, 2022
Exploring the ability of dihydropyrimidine-5-carboxamide and 5-benzyl-2,4-diaminopyrimidine-based analogues for the selective inhibition of L. major dihydrofolate reductase.European journal of medicinal chemistry, , Jan-15, Volume: 210, 2021
Design, synthesis and biological evaluation of novel pyrrolo[2,3-d]pyrimidine as tumor-targeting agents with selectivity for tumor uptake by high affinity folate receptors over the reduced folate carrier.Bioorganic & medicinal chemistry, , 06-15, Volume: 28, Issue:12, 2020
Designing Dihydrofolate Reductase Inhibitors as X-ray Radiosensitizers to Reverse Radioresistance of Cervical Cancer.ACS medicinal chemistry letters, , Jul-09, Volume: 11, Issue:7, 2020
Structural tuning of acridones for developing anticancer agents targeting dihydrofolate reductase.Bioorganic & medicinal chemistry letters, , 10-01, Volume: 29, Issue:19, 2019
Expansion of a novel lead targeting M. tuberculosis DHFR as antitubercular agents.Bioorganic & medicinal chemistry, , 04-01, Volume: 27, Issue:7, 2019
Discovery of Selective Toxoplasma gondii Dihydrofolate Reductase Inhibitors for the Treatment of Toxoplasmosis.Journal of medicinal chemistry, , 02-14, Volume: 62, Issue:3, 2019
Targeting dihydrofolate reductase: Design, synthesis and biological evaluation of novel 6-substituted pyrrolo[2,3-d]pyrimidines as nonclassical antifolates and as potential antitumor agents.European journal of medicinal chemistry, , Sep-15, Volume: 178, 2019
1,3,5-triazaspiro[5.5]undeca-2,4-dienes as selective Mycobacterium tuberculosis dihydrofolate reductase inhibitors with potent whole cell activity.European journal of medicinal chemistry, , Jan-20, Volume: 144, 2018
Inhibitors of dihydrofolate reductase as antitumor agents: design, synthesis and biological evaluation of a series of novel nonclassical 6-substituted pyrido[3,2-d]pyrimidines with a three- to five-carbon bridge.Bioorganic & medicinal chemistry, , 05-15, Volume: 26, Issue:9, 2018
Design, Synthesis, and Biological Evaluation of Coupled Bioactive Scaffolds as Potential Anticancer Agents for Dual Targeting of Dihydrofolate Reductase and Thioredoxin Reductase.Journal of medicinal chemistry, , 03-09, Volume: 60, Issue:5, 2017
Synthesis and evaluation of 5-(arylthio)-9H-pyrimido[4,5-b]indole-2,4-diamines as receptor tyrosine kinase and thymidylate synthase inhibitors and as antitumor agents.Bioorganic & medicinal chemistry letters, , 04-01, Volume: 27, Issue:7, 2017
Synthesis and antiproliferative activity of a series of novel 6-substituted pyrido[3,2-d]pyrimidines as potential nonclassical lipophilic antifolates targeting dihydrofolate reductase.European journal of medicinal chemistry, , Mar-10, Volume: 128, 2017
Design, synthesis, docking studies and biological evaluation of novel dihydro-1,3,5-triazines as human DHFR inhibitors.European journal of medicinal chemistry, , Jan-05, Volume: 125, 2017
Host dihydrofolate reductase (DHFR)-directed cycloguanil analogues endowed with activity against influenza virus and respiratory syncytial virus.European journal of medicinal chemistry, , Jul-28, Volume: 135, 2017
Synthesis, Antifolate and Anticancer Activities of N(5) -Substituted 8,10-Dideazatetrahydrofolate Analogues.Chemical biology & drug design, , Volume: 87, Issue:3, 2016
Discovery of Potent and Selective Leads against ACS medicinal chemistry letters, , Dec-08, Volume: 7, Issue:12, 2016
Charged Nonclassical Antifolates with Activity Against Gram-Positive and Gram-Negative Pathogens.ACS medicinal chemistry letters, , Jul-14, Volume: 7, Issue:7, 2016
Rational modification of the lead molecule: Enhancement in the anticancer and dihydrofolate reductase inhibitory activity.Bioorganic & medicinal chemistry letters, , Apr-15, Volume: 26, Issue:8, 2016
Synthesis, in vitro antitumor activity, dihydrofolate reductase inhibition, DNA intercalation and structure-activity relationship studies of 1,3,5-triazine analogues.Bioorganic & medicinal chemistry letters, , Jan-15, Volume: 26, Issue:2, 2016
Applying the designed multiple ligands approach to inhibit dihydrofolate reductase and thioredoxin reductase for anti-proliferative activity.European journal of medicinal chemistry, , Jun-10, Volume: 115, 2016
Design and Synthesis of a Focused Library of Diamino Triazines as Potential Mycobacterium tuberculosis DHFR Inhibitors.ACS medicinal chemistry letters, , Nov-12, Volume: 6, Issue:11, 2015
Structure-based design of new dihydrofolate reductase antibacterial agents: 7-(benzimidazol-1-yl)-2,4-diaminoquinazolines.Journal of medicinal chemistry, , Feb-13, Volume: 57, Issue:3, 2014
Synthesis and antiproliferative activity of 4-substituted-piperazine-1-carbodithioate derivatives of 2,4-diaminoquinazoline.European journal of medicinal chemistry, , Volume: 64, 2013
Design, synthesis, and molecular modeling of novel pyrido[2,3-d]pyrimidine analogues as antifolates; application of Buchwald-Hartwig aminations of heterocycles.Journal of medicinal chemistry, , Jun-13, Volume: 56, Issue:11, 2013
Structure-based selectivity optimization of piperidine-pteridine derivatives as potent Leishmania pteridine reductase inhibitors.Journal of medicinal chemistry, , Oct-11, Volume: 55, Issue:19, 2012
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
Mechanism inspired development of rationally designed dihydrofolate reductase inhibitors as anticancer agents.Journal of medicinal chemistry, , Jul-26, Volume: 55, 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
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
Non-classical antifolates. Part 2: synthesis, biological evaluation, and molecular modeling study of some new 2,6-substituted-quinazolin-4-ones.Bioorganic & medicinal chemistry, , Apr-15, Volume: 18, Issue:8, 2010
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 structures of 2,4-diaminofuro[2,3-d]pyrimidines as multireceptor tyrosine kinase and dihydrofolate reductase inhibitors.Bioorganic & medicinal chemistry, , Oct-15, Volume: 17, Issue:20, 2009
Novel 8-deaza-5,6,7,8-tetrahydroaminopterin derivatives as dihydrofolate inhibitor: design, synthesis and antifolate activity.European journal of medicinal chemistry, , Volume: 44, Issue:2, 2009
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
Synthesis of N-(5,7-diamino-3-phenyl-quinoxalin-2-yl)-3,4,5-substituted anilines and N-[4[(5,7-diamino-3-phenylquinoxalin-2-yl)amino]benzoyl]-l-glutamic acid diethyl ester: evaluation of in vitro anti-cancer and anti-folate activities.European journal of medicinal chemistry, , Volume: 43, Issue:1, 2008
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
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
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
Synthesis and biological evaluation of novel 2,4-diaminoquinazoline derivatives as SMN2 promoter activators for the potential treatment of spinal muscular atrophy.Journal of medicinal chemistry, , Feb-14, Volume: 51, Issue:3, 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
Novel boron-containing, nonclassical antifolates: synthesis and preliminary biological and structural evaluation.Journal of medicinal chemistry, , Jul-12, Volume: 50, Issue:14, 2007
Methotrexate gamma-hydroxamate derivatives as potential dual target antitumor drugs.Bioorganic & medicinal chemistry, , Feb-01, Volume: 15, Issue:3, 2007
Dual inhibitors of thymidylate synthase and dihydrofolate reductase as antitumor agents: design, synthesis, and biological evaluation of classical and nonclassical pyrrolo[2,3-d]pyrimidine antifolates(1).Journal of medicinal chemistry, , Feb-09, Volume: 49, Issue:3, 2006
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
Functional cloning of Bacillus anthracis dihydrofolate reductase and confirmation of natural resistance to trimethoprim.Antimicrobial agents and chemotherapy, , Volume: 48, Issue:12, 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 classical and nonclassical, partially restricted, linear, tricyclic 5-deaza antifolates.Journal of medicinal chemistry, , Nov-07, Volume: 45, Issue:23, 2002
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, 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
Computational predictions of binding affinities to dihydrofolate reductase: synthesis and biological evaluation of methotrexate analogues.Journal of medicinal chemistry, , Oct-19, Volume: 43, Issue:21, 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
The structure-based design and synthesis of selective inhibitors of Trypanosoma cruzi dihydrofolate reductase.Bioorganic & medicinal chemistry letters, , May-17, Volume: 9, Issue:10, 1999
Synthesis and potent antifolate activity and cytotoxicity of B-ring deaza analogues of the nonpolyglutamatable dihydrofolate reductase inhibitor Nalpha-(4-amino-4-deoxypteroyl)-Ndelta-hemiphthaloyl- L-ornithine (PT523).Journal of medicinal chemistry, , Dec-17, Volume: 41, Issue:26, 1998
Synthesis and biological evaluation of DL-4,4-difluoroglutamic acid and DL-gamma,gamma-difluoromethotrexate.Journal of medicinal chemistry, , Jan-05, Volume: 39, Issue:1, 1996
Synthesis and biological activity of folic acid and methotrexate analogues containing L-threo-(2S,4S)-4-fluoroglutamic acid and DL-3,3-difluoroglutamic acid.Journal of medicinal chemistry, , Jan-05, Volume: 39, Issue:1, 1996
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
Synthesis and biological evaluation of N alpha-(4-amino-4-deoxy-10-methylpteroyl)-DL-4,4-difluoroornithine.Journal of medicinal chemistry, , Jun-21, Volume: 39, Issue:13, 1996
Effect of bridge region variation on antifolate and antitumor activity of classical 5-substituted 2,4-diaminofuro[2,3-d]pyrimidines.Journal of medicinal chemistry, , Sep-15, Volume: 38, Issue:19, 1995
2,4-Diamino-5-substituted-quinazolines as inhibitors of a human dihydrofolate reductase with a site-directed mutation at position 22 and of the dihydrofolate reductases from Pneumocystis carinii and Toxoplasma gondii.Journal of medicinal chemistry, , Mar-03, Volume: 38, Issue:5, 1995
Classical and nonclassical furo[2,3-d]pyrimidines as novel antifolates: synthesis and biological activities.Journal of medicinal chemistry, , Apr-15, Volume: 37, Issue:8, 1994
Synthesis and biological activity of N omega-hemiphthaloyl-alpha,omega- diaminoalkanoic acid analogues of aminopterin and 3',5-dichloroaminopterin.Journal of medicinal chemistry, , Jul-08, Volume: 37, Issue:14, 1994
Side chain modified 5-deazafolate and 5-deazatetrahydrofolate analogues as mammalian folylpolyglutamate synthetase and glycinamide ribonucleotide formyltransferase inhibitors: synthesis and in vitro biological evaluation.Journal of medicinal chemistry, , May-01, Volume: 35, Issue:9, 1992
Folate analogues. 34. Synthesis and antitumor activity of non-polyglutamylatable inhibitors of dihydrofolate reductase.Journal of medicinal chemistry, , Volume: 34, Issue:1, 1991
Synthesis and biological activity of the 2-desamino and 2-desamino-2-methyl analogues of aminopterin and methotrexate.Journal of medicinal chemistry, , Volume: 34, Issue:1, 1991
Synthesis and biological activity of methotrexate analogues with two acid groups and a hydrophobic aromatic ring in the side chain.Journal of medicinal chemistry, , Volume: 34, Issue:2, 1991
Analogues of methotrexate and aminopterin with gamma-methylene and gamma-cyano substitution of the glutamate side chain: synthesis and in vitro biological activity.Journal of medicinal chemistry, , Volume: 34, Issue:1, 1991
Synthesis and antifolate properties of 9-alkyl-10-deazaminopterins.Journal of medicinal chemistry, , Volume: 33, Issue:1, 1990
Inhibition of mammalian folylpolyglutamate synthetase and human dihydrofolate reductase by 5,8-dideaza analogues of folic acid and aminopterin bearing a terminal L-ornithine.Journal of medicinal chemistry, , Volume: 32, Issue:7, 1989
The 2-desamino and 2-desamino-2-methyl analogues of aminopterin do not inhibit dihydrofolate reductase but are potently toxic to tumor cells in culture.Journal of medicinal chemistry, , Volume: 32, Issue:3, 1989
Comparison of the biological effects of selected 5,8-dideazafolate analogues with their 2-desamino counterparts.Journal of medicinal chemistry, , Volume: 32, Issue:4, 1989
Inhibition of murine thymidylate synthase and human dihydrofolate reductase by 5,8-dideaza analogues of folic acid and aminopterin.Journal of medicinal chemistry, , Volume: 31, Issue:2, 1988
Folate analogues. 26. Syntheses and antifolate activity of 10-substituted derivatives of 5,8-dideazafolic acid and of the poly-gamma-glutamyl metabolites of N10-propargyl-5,8-dideazafolic acid (PDDF).Journal of medicinal chemistry, , Volume: 29, Issue:9, 1986
Folate analogues. 21. Synthesis and antifolate and antitumor activities of N10-(cyanomethyl)-5,8-dideazafolic acid.Journal of medicinal chemistry, , Volume: 26, Issue:4, 1983
Convenient synthesis of 10-deazaaminopterin via a pteridine ylide.Journal of medicinal chemistry, , Volume: 23, Issue:3, 1980
Folate analogues altered in the C9-N10 bridge region. 16. Synthesis and antifolate activity of 11-thiohomoaminopterin.Journal of medicinal chemistry, , Volume: 23, Issue:8, 1980
Synthesis and biological activity of 8-oxadihydropteridines.Journal of medicinal chemistry, , Volume: 22, Issue:6, 1979
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
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
Effect of bridge region variation on antifolate and antitumor activity of classical 5-substituted 2,4-diaminofuro[2,3-d]pyrimidines.Journal of medicinal chemistry, , Sep-15, Volume: 38, Issue:19, 1995
Synthesis and potent antifolate activity and cytotoxicity of B-ring deaza analogues of the nonpolyglutamatable dihydrofolate reductase inhibitor Nalpha-(4-amino-4-deoxypteroyl)-Ndelta-hemiphthaloyl- L-ornithine (PT523).Journal of medicinal chemistry, , Dec-17, Volume: 41, Issue:26, 1998
2,4-Diamino-5-substituted-quinazolines as inhibitors of a human dihydrofolate reductase with a site-directed mutation at position 22 and of the dihydrofolate reductases from Pneumocystis carinii and Toxoplasma gondii.Journal of medicinal chemistry, , Mar-03, Volume: 38, Issue:5, 1995
Synthesis and biological activity of N omega-hemiphthaloyl-alpha,omega- diaminoalkanoic acid analogues of aminopterin and 3',5-dichloroaminopterin.Journal of medicinal chemistry, , Jul-08, Volume: 37, Issue:14, 1994
Synthesis and biological activity of the 2-desamino and 2-desamino-2-methyl analogues of aminopterin and methotrexate.Journal of medicinal chemistry, , Volume: 34, Issue:1, 1991
Synthesis and biological activity of methotrexate analogues with two acid groups and a hydrophobic aromatic ring in the side chain.Journal of medicinal chemistry, , Volume: 34, Issue:2, 1991
Analogues of methotrexate and aminopterin with gamma-methylene and gamma-cyano substitution of the glutamate side chain: synthesis and in vitro biological activity.Journal of medicinal chemistry, , Volume: 34, Issue:1, 1991
Novel fluorinated antifolates. Enzyme inhibition and cytotoxicity studies on 2'- and 3'-fluoroaminopterin.Journal of medicinal chemistry, , Volume: 26, Issue:8, 1983
Structure-based design of new dihydrofolate reductase antibacterial agents: 7-(benzimidazol-1-yl)-2,4-diaminoquinazolines.Journal of medicinal chemistry, , Feb-13, Volume: 57, Issue:3, 2014
Structure-based design of new DHFR-based antibacterial agents: 7-aryl-2,4-diaminoquinazolines.Bioorganic & medicinal chemistry letters, , Sep-15, Volume: 21, Issue:18, 2011
Iclaprim, a novel diaminopyrimidine with potent activity on trimethoprim sensitive and resistant bacteria.Bioorganic & medicinal chemistry letters, , Dec-01, Volume: 13, Issue:23, 2003
Synthesis and biological activity of N omega-hemiphthaloyl-alpha,omega- diaminoalkanoic acid analogues of aminopterin and 3',5-dichloroaminopterin.Journal of medicinal chemistry, , Jul-08, Volume: 37, Issue:14, 1994
Folate analogues. 34. Synthesis and antitumor activity of non-polyglutamylatable inhibitors of dihydrofolate reductase.Journal of medicinal chemistry, , Volume: 34, Issue:1, 1991
Therapeutic progression of quinazolines as targeted chemotherapeutic agents.European journal of medicinal chemistry, , Feb-05, Volume: 211, 2021
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
Potent inhibition of thymidylate synthase by two series of nonclassical quinazolines.Journal of medicinal chemistry, , Volume: 33, Issue:7, 1990
Comparison of the biological effects of selected 5,8-dideazafolate analogues with their 2-desamino counterparts.Journal of medicinal chemistry, , Volume: 32, Issue:4, 1989
Inhibition of murine thymidylate synthase and human dihydrofolate reductase by 5,8-dideaza analogues of folic acid and aminopterin.Journal of medicinal chemistry, , Volume: 31, Issue:2, 1988
Folate analogues. 21. Synthesis and antifolate and antitumor activities of N10-(cyanomethyl)-5,8-dideazafolic acid.Journal of medicinal chemistry, , Volume: 26, Issue:4, 1983
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
FDA-approved pyrimidine-fused bicyclic heterocycles for cancer therapy: Synthesis and clinical application.European journal of medicinal chemistry, , Mar-15, Volume: 214, 2021
Design, synthesis and biological evaluation of novel pyrrolo[2,3-d]pyrimidine as tumor-targeting agents with selectivity for tumor uptake by high affinity folate receptors over the reduced folate carrier.Bioorganic & medicinal chemistry, , 06-15, Volume: 28, Issue:12, 2020
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
Novel approaches for targeting thymidylate synthase to overcome the resistance and toxicity of anticancer drugs.Journal of medicinal chemistry, , Sep-23, Volume: 53, Issue:18, 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
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
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
Dual inhibitors of thymidylate synthase and dihydrofolate reductase as antitumor agents: design, synthesis, and biological evaluation of classical and nonclassical pyrrolo[2,3-d]pyrimidine antifolates(1).Journal of medicinal chemistry, , Feb-09, Volume: 49, Issue:3, 2006
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
Novel 2-amino-4-oxo-5-arylthio-substituted-pyrrolo[2,3-d]pyrimidines as nonclassical antifolate inhibitors of thymidylate synthase.Bioorganic & medicinal chemistry letters, , May-02, Volume: 15, Issue:9, 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
Antibacterial agent discovery using thymidylate synthase biolibrary screening.Journal of medicinal chemistry, , Oct-05, Volume: 49, Issue:20, 2006
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
Enables
This protein enables 7 target(s):
| Target | Category | Definition |
|---|
| mRNA regulatory element binding translation repressor activity | molecular function | Antagonizes the ribosome-mediated translation of mRNA into a polypeptide via direct binding (through a selective and non-covalent interaction) to nucleic acid. [GOC:clt, GOC:vw, PMID:29061112, PMID:7523370] |
| mRNA binding | molecular function | Binding to messenger RNA (mRNA), an intermediate molecule between DNA and protein. mRNA includes UTR and coding sequences, but does not contain introns. [GOC:kmv, GOC:pr, SO:0000234] |
| dihydrofolate reductase activity | molecular function | Catalysis of the reaction: 5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+. [EC:1.5.1.3] |
| folic acid binding | molecular function | Binding to folic acid, pteroylglutamic acid. Folic acid is widely distributed as a member of the vitamin B complex and is essential for the synthesis of purine and pyrimidines. [GOC:jl, ISBN:0198506732] |
| NADPH binding | molecular function | Binding to the reduced form, NADPH, of nicotinamide-adenine dinucleotide phosphate, a coenzyme involved in many redox and biosynthetic reactions. [GOC:mah] |
| sequence-specific mRNA binding | molecular function | Binding to messenger RNA (mRNA) of a specific nucleotide composition or a specific sequence motif. [PMID:11886857] |
| NADP binding | molecular function | Binding to nicotinamide-adenine dinucleotide phosphate, a coenzyme involved in many redox and biosynthetic reactions; binding may be to either the oxidized form, NADP+, or the reduced form, NADPH. [GOC:ai] |
Located In
This protein is located in 2 target(s):
| Target | Category | Definition |
|---|
| mitochondrion | cellular component | A semiautonomous, self replicating organelle that occurs in varying numbers, shapes, and sizes in the cytoplasm of virtually all eukaryotic cells. It is notably the site of tissue respiration. [GOC:giardia, ISBN:0198506732] |
| cytosol | cellular component | The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. [GOC:hjd, GOC:jl] |
Active In
This protein is active in 1 target(s):
| Target | Category | Definition |
|---|
| mitochondrion | cellular component | A semiautonomous, self replicating organelle that occurs in varying numbers, shapes, and sizes in the cytoplasm of virtually all eukaryotic cells. It is notably the site of tissue respiration. [GOC:giardia, ISBN:0198506732] |
Involved In
This protein is involved in 11 target(s):
| Target | Category | Definition |
|---|
| tetrahydrobiopterin biosynthetic process | biological process | The chemical reactions and pathways resulting in the formation of tetrahydrobiopterin, the reduced form of biopterin (2-amino-4-hydroxy-6-(1,2-dihydroxypropyl)-pteridine). It functions as a hydroxylation coenzyme, e.g. in the conversion of phenylalanine to tyrosine. [ISBN:0198506732] |
| one-carbon metabolic process | biological process | The chemical reactions and pathways involving the transfer of one-carbon units in various oxidation states. [GOC:hjd, GOC:mah, GOC:pde] |
| negative regulation of translation | biological process | Any process that stops, prevents, or reduces the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of proteins by the translation of mRNA or circRNA. [GOC:isa_complete] |
| axon regeneration | biological process | The regrowth of axons following their loss or damage. [GOC:dgh, GOC:dph, GOC:tb] |
| response to methotrexate | biological process | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a methotrexate stimulus. Methotrexate is 4-amino-10-methylformic acid, a folic acid analogue that is a potent competitive inhibitor of dihydrofolate reductase. [GOC:ef, GOC:mah, ISBN:0198506732] |
| dihydrofolate metabolic process | biological process | The chemical reactions and pathways involving dihydrofolate, the dihydroxylated derivative of folate. [ISBN:0198506732] |
| tetrahydrofolate metabolic process | biological process | The chemical reactions and pathways involving tetrahydrofolate, 5,6,7,8-tetrahydrofolic acid, a folate derivative bearing additional hydrogens on the pterin group. [ISBN:0198506732] |
| tetrahydrofolate biosynthetic process | biological process | The chemical reactions and pathways resulting in the formation of tetrahydrofolate, 5,6,7,8-tetrahydrofolic acid, a folate derivative bearing additional hydrogens on the pterin group. [ISBN:0198506732] |
| folic acid metabolic process | biological process | The chemical reactions and pathways involving folic acid, pteroylglutamic acid. Folic acid is widely distributed as a member of the vitamin B complex and is essential for the synthesis of purine and pyrimidines. [ISBN:0198506732] |
| positive regulation of nitric-oxide synthase activity | biological process | Any process that activates or increases the activity of the enzyme nitric-oxide synthase. [GOC:ai] |
| regulation of removal of superoxide radicals | biological process | Any process that modulates the frequency, rate or extent of removal of superoxide radicals. [GOC:obol] |