engleski

Anti-Pneumocystis carinii pneumonia activity of dicationic diaryl methylpyrimidines

Synthesis of 2, 4-bis-(4-amidinophenyl)-6-methylpyrimidine 5, 2, 4-bis-[(4-imidazolin-2-yl)phenyl]-6-methylpyrimidine 6, 2, 4-bis[(4-N-i-propylamidino)phenyl]-6-methylpyrimidine 7, and 2, 4-bis[(4-N-isopentylamidino)phenyl]-6-methylpyrimidine starting from 4-bromobenzamidine and 4'-bromoacetophenone is reported. The synthesis of 2, 4-bis-(4-amidinophenyl)-5-methylpyrimidine 12 and 2, 4-bis-[(4-imidazolin-2-yl)phenyl]-5-methylpyrimidine 13, also beginning with 4-bromobenzamidine and 4'-bromopropiophenone is described. A synthesis of 4, 6-bis-(4-amidinophenyl)-2-methylpyrimidine 17, 4, 6-bis-[(4-imidazolin-2-yl)phenyl]-2-methylpyrimidine 18, 4, 6-bis[(4-N-i-propylamidino)phenyl]-2-methylpyrimidine 19 and 4, 6-bis[(4-N-n-propylamidino)phenyl]-2-methylpyrimidine 20 starting from acetamidine and 1, 3-bis(4-bromophenyl)propenone is reported. Compounds 5-7 and 17-20 all bind strongly to the minor groove of poly-dA.dT whereas 8, 12 and 13 bind less tightly as judged by their Delta T-m values. A similar trend was noted for binding of these compounds to the 12-mer-d(CGCGAATTCGCG)(2). Compounds 5, 7, and 17 are more active and less toxic than pentamidine at its effective dose when evaluated against Pneumocystis carinii pneumonia (PCP) in the immunosuppressed rat model.

pneumocystis carinii pneumonia; diaryldiamidines; DNA acid binding-agents; inor-groove; DNA; d(cgcgaattcgcg)(2); benzimidazoles; sequences; berenil; GC

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