Synthesis of 2,4-Diaminopteridines with Bulky Lipophilic Groups at the 6-Position as Inhibitors of Pneumocystis carinii, Toxoplasma gondii, and Mammalian Dihydrofolate Reductase
| Autor: | Rosowsky Andre, Forsch Ronald A., Queener Sherry F., Bertino Joseph R. |
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| Jazyk: | angličtina |
| Rok vydání: | 1997 |
| Předmět: | |
| Zdroj: | Pteridines, Vol 8, Iss 3, Pp 173-187 (1997) |
| Druh dokumentu: | article |
| ISSN: | 0933-4807 2195-4720 |
| DOI: | 10.1515/pteridines.1997.8.3.173 |
| Popis: | Ten previously undescribed 2,4-diamino-6-(2-naphthylamino )methylpteridines with lipophilic chlorine or long-chain alkyl groups on the naphthyl moiety and either hydrogen or a methyl group on N 10 were synthesized from the appropriate 2-naphthylamine or N-methyl-2-naphthylamine by reaction with 2-amino-5-chloromethylpyrazine-3-carbonitrile and ring closure with guanidine . One analogue with a methyl group at the 7 -position was also prepared. The N 10 -unsubstituted analogues were consistently less active than the N1o-methyl analogues as inhibitors of Pneumocystis carin ii, Toxoplasma gondii, and rat liver dihydrofolate reductase. However the potency of the series as a whole was relatively low against all three enzymes, with the best inhibitors giving ICoo values only in the 0.1-1.0 ~M range and several giving IC50 values in the 10-100 ~M range. Moreover, while several compounds with ICso values of |
| Databáze: | Directory of Open Access Journals |
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