Synthesis and structure-activity relationships of 2-pyridones: II. 8- (fluoro-substituted pyrrolidinyl)-2-pyridones as antibacterial agents

Bioorganic and Medicinal Chemistry Letters

Volumn 8, Issue 15, 1998, Pages 1953-1958

  Li, Qun ^a   Wang, Weibo ^a   Berst, Kristine B ^a   Claiborne, Akiyo ^a   Hasvold, Lisa ^a   Raye, Kathleen ^a   Tufano, Michael ^a   Nilius, Angela ^a   Shen, Linus L ^a   Flamm, Robert ^a   Alder, Jeff ^a   Marsh, Kennan ^a   Crowell, DeAnne ^a   Chu, Daniel T W ^a   Planner, Jacob J ^a  

^a ABBOTT LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 PYRIDONE DERIVATIVE; BACTERIAL DNA; DNA TOPOISOMERASE (ATP HYDROLYSING);

ANTIBACTERIAL ACTIVITY; ARTICLE; DRUG EFFICACY; DRUG POTENCY; DRUG SYNTHESIS; ESCHERICHIA COLI; GRAM NEGATIVE BACTERIUM; METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS; MOUSE; NONHUMAN; PSEUDOMONAS; STAPHYLOCOCCUS; STAPHYLOCOCCUS AUREUS; STRUCTURE ACTIVITY RELATION;

ANIMALS; ANTI-BACTERIAL AGENTS; BIOLOGICAL AVAILABILITY; GRAM-NEGATIVE BACTERIA; GRAM-POSITIVE BACTERIA; HALF-LIFE; MICROBIAL SENSITIVITY TESTS; PYRIDONES; RATS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0032483068     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(98)00355-2     Document Type: Article

References (21)

1. 2. Li, Q.; Chu, D. T.; Claiborne, A.; Cooper, C. S.; Lee, C. M.; Raye, K.; Berst, K. B.; Donner, P.; Wang, W., Hasvold, L.; Fung, A.; Ma, Z.; Tufanp, 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. J. Med. Chem. 1996, 39, 3070.
2. 3. For other 2-pyridone related papers, see: (a) Ma, Z.; Chu, D. T. W.; Li, Q.; Shen, L. L.; Fung, A.; Cooper, C. S.; Wang, W.; Wang, S.; Flamm, R. K.; Nilius, A.; Alder, J. D.; Tanaka, S. K.; Or, Y.; Plattner, J. J. 37th ICAAC, 1997, Abstract F169.
3. (b) Park, T-H.; Nam, K-S.; Ha, Y-H.; Choi, Y-K.; Choi, Y-J.; Kong, J-Y.; Kim, Y-H. 37th ICAAC, 1997, Abstract 173.
4. (c) Klein, L. L.; DeGoey, D. A.; Thomas, S. A.; Yeung, C. M.; Leone, C. L.; Grampovnik, D. J.; Chu, D. T.; Lartey, P. A. Bioorg. Med Chem. Lett. 1997, 7, 1167.
5. (d) Flamm, R. K.; Vojtko, C.; Chu, D. T.; Li, Q.; Beyer, J.; Hensey, D.; Ramer, N.; Clement, J. J.; Tanaka, S. K. Antimicrob. Agents Chemother. 1995, 39, 964.
6. (e) Eliopoulos, G. M.; Wennersten, C. B.; Cole, G.; Chu, D.; Pizzuti, D.; Moellering, R. C., Jr. Antimicrob. Agents Chemother. 1995, 39, 850.
7. (f) Alder, J.; Clement, J; Meulbroek, J.; Shipkowitz, N.; Mitten, M.; Jarvis, K.; Oleksijew, A.; Hutch, T., Sr.; Paige, L.; Flamm, R.; Chu, D.; Tanaka, K. Antimicrob. Agents Chemother. 1995, 39, 971.
8. (g) Fromtling, R. A. Drugs Fut. 1995, 20, 1103.
9. 4. Shen, L. L. Advances in Pharmacology 1994, 29a, 285.
10. 5. K. Hayashi and coworkers disclosed at 37th ICAAC that with certain combinations of substitutions at the 7- and 8-positions, the quinolones without the 6-fluorine were as active as the ones with the 6-fluorine, while having greatly reduced side effects. Hayashi, K.; Todo, Y.; Hamamoto, S.; Ojima, K.; Yamada, M.; Kito, T.; Takahata, M.; Watanabe, Y.; Narita, H. 37th ICAAC 1997, Abstract 158.
11. 6 Li, Q.; Claiborne, A.; Chu, D. T. W.; Lee, C. M.; Raye, K. A.; Berst, K.; Ma, Z.; Wang, W.; Shen, L. L.; Flamm, R.; Nilius, A.; Alder, J.; Marsh, K.; Shortridge, V. D.; Tanaka, S. K.; Seif, L.; Cooper, C. S.; Fung, A.; Tufano, M.; Melcher, L. M.; Henry, R.; Klein, L.; Plattner, J. J. Presented in part at the 35th ICAAC 1995, Abstract F8.
12. 7. Bouzard, D.; Cesare, P. Di; Essiz, M.; Jacquet, J. P.; Kiechel, J. R.; Remuzon, P.; Weber, A.; Oki, T.; Masuyoshi, M.; Kessler, R. E.; Fung-Tomc, J.; Desiderio, J. J. Med. Chem. 1990, 33, 1344.
13. 8. Racemic 8 and 18 were separated by preparative HPLC using a Chiralpak column eluting with hexanes/ethanol (90/10). The compounds with lower retention time after cleavage of the benzyl group were assigned arbitrarily as 3R, 4R (2a-RR) and 3R,4S (2d-RS), respectively. The compounds with higher retention time after cleavage of the benzyl group were assigned arbitrarily as 3S,4S (2a-SS) and 3S,4R (2d-SR), respectively.
14. 9. Laborde, E. Tetrahedron Lett. 1992, 33, 6607, and references therein.
15. 10. Saito, A; Uesato, S; Iwata, H; Ao, H; Kuroda, T; Kawasaki, K; Morigushi, A; Ikeda, Y. WO 9514794-A1, 1994.
16. 11. Kitani, H.; Kuroda, T.; Moriguchi, A.; Ao, H.; Hirayama, F.; Ikeda, Y.; Kawakita, T. Bioorg. Med. Chem. Lett. 1997, 7, 515.
17. 12. The configurations were assigned arbitrarily.
18. 13. National Committee for Clinical Laboratory Standards 1993. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Approved standard M7-A3; National Committee for Clinical Laboratory Standards; Villanova, PA
19. 14. (a) Shen, L. L.; Baranowski, J.; Fostel, J.; Montgomery, D. A.; Lartey, P. A. Antimicrob. Agents Chemother. 1992, 36, 2778.
20. (b) Shen, L. L.; Kohlbrenner, W. E.; Weigl, D.; Baranowski, J. J. Biol. Chem. 1989a, 264, 2973.
21. 15. Clement, J. C.; Tanaka, S. K.; Alder, J, D.; Vojtko, C.; Beyer, J.; Hensey, D.; Ramer, N.; McDaniel, D.; Chu, D. T. W. Antimocrob. Agents Chemother. 1994, 38, 1071.