pemetrexed has been researched along with pyrimidine* in 3 studies
1 review(s) available for pemetrexed and pyrimidine
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FDA-approved pyrimidine-fused bicyclic heterocycles for cancer therapy: Synthesis and clinical application.
Considerable progress has been made in the development of anticancer agents over the past few decades, and a lot of new anticancer agents from natural and synthetic sources have been produced. Among heterocyclic compounds, pyrimidine-fused bicyclic heterocycles possess a variety of biological activities such as anticancer, antiviral, etc. To date, 147 pyrimidine-fused bicyclic heterocycles have been approved for clinical assessment or are currently being used in clinic, 57 of which have been approved by FDA for clinical treatment of various diseases, and 22 of them are being used in the clinic for the treatment of different cancers. As the potentially privileged scaffolds, pyrimidine-fused bicyclic heterocycles may be used to discover new drugs with similar biological targets and improved therapeutic efficacy. This review aims to provide an overview of the anticancer applications and synthetic routes of 22 approved pyrimidine-fused bicyclic heterocyclic drugs in clinic. Topics: Antineoplastic Agents; Bridged Bicyclo Compounds, Heterocyclic; Humans; Molecular Structure; Neoplasms; Pyrimidines; United States; United States Food and Drug Administration | 2021 |
2 other study(ies) available for pemetrexed and pyrimidine
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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.
Classical antifolates (4-7) with a tricyclic benzo[4,5]thieno[2,3-d]pyrimidine scaffold and a flexible and rigid benzoylglutamate were synthesized as dual thymidylate synthase (TS) and dihydrofolate reductase (DHFR) inhibitors. Oxidative aromatization of ethyl 2-amino-4-methyl-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxylate (±)-9 to ethyl 2-amino-4-methyl-1-benzothiophene-3-carboxylate 10 with 10% Pd/C was a key synthetic step. Compounds with 2-CH₃ substituents inhibited human (h) TS (IC₅₀ =0.26-0.8 μM), but not hDHFR. Substitution of the 2-CH₃ with a 2-NH₂ increases hTS inhibition by more than 10-fold and also affords excellent hDHFR inhibition (IC₅₀ = 0.09-0.1 μM). This study shows that the tricyclic benzo[4,5]thieno[2,3-d]pyrimidine scaffold is highly conducive to single hTS or dual hTS-hDHFR inhibition depending on the 2-position substituents. The X-ray crystal structures of 6 and 7 with hDHFR reveal, for the first time, that tricyclics 6 and 7 bind with the benzo[4,5]thieno[2,3-d]pyrimidine ring in the folate binding mode with the thieno S mimicking the 4-amino of methotrexate. Topics: Crystallography, X-Ray; Drug Design; Enzyme Inhibitors; Folic Acid Antagonists; Humans; Molecular Conformation; Pyrimidines; Tetrahydrofolate Dehydrogenase; Thymidylate Synthase | 2011 |
Synthesis and biological activity of a novel series of 6-substituted thieno[2,3-d]pyrimidine antifolate inhibitors of purine biosynthesis with selectivity for high affinity folate receptors over the reduced folate carrier and proton-coupled folate transpo
A series of seven 2-amino-4-oxo-6-substituted thieno[2,3-d]pyrimidines with bridge length variations (from 2 to 8 carbon atoms) were synthesized as selective folate receptor (FR) alpha and beta substrates and as antitumor agents. The syntheses were accomplished from appropriate allylalcohols and 4-iodobenzoate to afford the aldehydes, which were converted to the appropriate 2-amino-4-carbethoxy-5-substituted thiophenes 23-29. Cyclization with chloroformamidine afforded the thieno[2,3-d]pyrimidines 30-36, which were hydrolyzed and coupled with diethyl-L-glutamate, followed by saponification, to give the target compounds 2-8. Compounds 3-6 were potent growth inhibitors (IC(50) 4.7-334 nM) of human tumor cells (KB and IGROV1) that express FRs. In addition, compounds 3-6 inhibited the growth of Chinese hamster ovary (CHO) cells that expressed FRs but not the reduced folate carrier (RFC) or proton-coupled folate transporter (PCFT). However, the compounds were inactive toward CHO cells that lacked FRs but contained either the RFC or PCFT. By nucleoside and 5-amino-4-imidazole carboxamide (AICA) protection studies, along with in vitro and in situ enzyme activity assays, the mechanism of antitumor activity was identified as the dual inhibition of glycinamide ribonucleotide formyltransferase and, likely, AICA ribonucleotide formyltransferase. The dual inhibitory activity of the active thieno[2,3-d]pyrimidine antifolates and the FR specificity represent unique mechanistic features for these compounds distinct from all other known antifolates. The potent inhibitory effects of compounds 3-6 toward cells expressing FRs but not PCFT provide direct evidence that cellular uptake of this series of compounds by FRs does not depend on the presence of PCFT and argues that direct coupling between these transporters is not obligatory. Topics: Animals; Anion Transport Proteins; Antineoplastic Agents; Biological Transport; Carrier Proteins; Cell Proliferation; CHO Cells; Cricetinae; Cricetulus; Folate Receptors, GPI-Anchored; Folic Acid Antagonists; Gene Expression Regulation; Humans; Hydrogen Bonding; Membrane Transport Proteins; Nucleosides; Phosphoribosylaminoimidazolecarboxamide Formyltransferase; Protons; Purines; Pyrimidines; Receptors, Cell Surface; Reduced Folate Carrier Protein; Substrate Specificity; Transfection | 2009 |