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
| Autor: | Kenneth Lane, Edward Aig, Barbara S. Rauckman, Barbara Roth |
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| Rok vydání: | 1980 |
| Předmět: |
Models
Molecular Pyrimidine Alkylation Stereochemistry Medicinal chemistry Trimethoprim Mannich Bases chemistry.chemical_compound Drug Discovery Dihydrofolate reductase medicine Escherichia coli Methods Phenol heterocyclic compounds Phenols biology Bacteria Raney nickel chemistry Yield (chemistry) biology.protein Molecular Medicine Folic Acid Antagonists medicine.drug |
| Zdroj: | Journal of medicinal chemistry. 23(5) |
| ISSN: | 0022-2623 |
| Popis: | The preparation of a wide variety of 6-substituted trimethoprim analogues was readily accomplished by the reaction of 2,4-diamino-6-substituted-pyrimidines with 2,6-dimethoxy-4-[(N,N-dimethylamino)methyl]phenol at 120--160 degrees C. The less reactive 2,6-dialkyl-4-[(N,N-dimethylamino)methyl]phenols reacted successfully with 2,4-diamino-6-(alkylthio)pyrimidines to give 5-(substituted benzyl)pyrimidines. The phenolic groups of the products were alkylated in high yield when a nonreactive 6-substituent was present in the pyrimidine ring. 6-(Alkylthio) groups were easily removed with Raney nickel. Trimethoprim was thus obtained in high yield from its 6-(methylthio) counterpart. The 6-substituted trimethoprim analogues all had low activity as inhibitors of Escherichia coli dihydrofolate reductase and as antibacterial agents. |
| Databáze: | OpenAIRE |
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