Abstract
A new series of 2,4-diaminopyrido[2,3-d]pyrimidine based antifolates 1-3 were synthesized through an efficient conversion of 2-pivaloyl-4-oxo-6-ethynylpyrido[2,3-d]pyrimidine 5 to the corresponding 4-amino analog 7 via the activated 1,2,4-triazole intermediate 6. Compound 7 was used as the key intermediate for the preparation of the final products. The detailed biological evaluation of these compounds both as antineoplastic and antiarthritic agents will be discussed.
MeSH terms
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / chemistry
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Arthritis, Experimental / drug therapy*
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Drug Evaluation, Preclinical
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Drug Screening Assays, Antitumor
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology
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Folic Acid Antagonists / chemical synthesis
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Folic Acid Antagonists / chemistry*
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Folic Acid Antagonists / pharmacology*
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Glutamates / chemistry
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Glutamates / pharmacology
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Guanine / analogs & derivatives
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Guanine / chemistry
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Guanine / pharmacology
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Hydroxymethyl and Formyl Transferases / antagonists & inhibitors
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Leukemia / drug therapy
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Lymphoma, Non-Hodgkin / drug therapy
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Mice
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Pemetrexed
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Peptide Synthases / metabolism
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Phosphoribosylglycinamide Formyltransferase
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Pyrimidines / chemistry
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Rats
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Structure-Activity Relationship
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Tetrahydrofolates / chemistry
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Tetrahydrofolates / pharmacology
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Thymidylate Synthase / antagonists & inhibitors
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Antineoplastic Agents
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Enzyme Inhibitors
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Folic Acid Antagonists
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Glutamates
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Pyrimidines
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Tetrahydrofolates
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Pemetrexed
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Guanine
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lometrexol
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Thymidylate Synthase
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Hydroxymethyl and Formyl Transferases
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Phosphoribosylglycinamide Formyltransferase
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Peptide Synthases
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folylpolyglutamate synthetase