| Autor: |
Li, Q., Chu, D. T. W., Claiborne, A., Cooper, C. S., Lee, C. M., Raye, K., Berst, K. B., Donner, P., Wang, W., Hasvold, L., Fung, A., Ma, Z., Tufano, M., Flamm, R., Shen, L. L., Baranowski, J., Nilius, A., Alder, J., Meulbroek, J., Marsh, K., Crowell, D., Hui, Y., Seif, L., Melcher, L. M., Henry, R., Spanton, S., Faghih, R., Klein, L. L., Tanaka, S. K., Plattner, J. J. |
| Zdroj: |
Journal of Medicinal Chemistry; August 2, 1996, Vol. 39 Issue: 16 p3070-3088, 19p |
| Abstrakt: |
Two novel series of 2-pyridones were synthesized by transposition of the nitrogen of 4-quinolones to the bridgehead position. This subtle interchange of the nitrogen atom with a carbon atom yielded two novel heterocyclic nuclei, pyrido[1,2-a]pyrimidine and quinolizine, which had not previously been evaluated as antibacterial agents and were found to be potent inhibitors of DNA gyrase. Quinolizines with a methyl group at the 9-position such as (S)-45a (ABT-719) demonstrate exceptional broad spectrum antibacterial activity. Most notably, they are active against resistant bacteria such as methicillin-resistant Staphylococcus aureus, vancomycin-resistant strains of enterococci, and ciprofloxacin-resistant organisms. In addition, 2-pyridones also possess favorable physiochemical and pharmacokinetic properties. These 2-pyridones were synthesized from the commercially available starting materials by 10−17 linear transformations. The structure of an adduct yielded by this sequence, (S)-45a (ABT-719), was determined by X-ray crystallographic analysis. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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