含氟喹啉酮衍生物之合成及抗菌 活性研究

Studies on the Synthesis and Antibacterial Activities of Fluoroquinolone Derivaties

洪照棠(Chao-Tang Hung)

指導教授 ： 曾誠齊

高雄醫學大學/藥學院/藥學研究所碩士在職專班/碩士(2006年)

摘要

近年來，細菌對許多一般常見的抗生素（例如：ß-lactam antibiotics 和 macrolides）已產生抗藥性，這已對全球公共衛生產生了嚴重的威脅。而現在所介紹的氟喹啉酮類藥物（例如：norfloxacin 和ciprofloxacin），它提供了有效的武器去對抗細菌，因為它具有獨特的作用方式，且可以抑制細菌的DNA gyrase，以及具有合適的藥物機轉和結構。合成新的氟喹啉酮類藥物和對於抗菌活性的評估與探討其結構與活性的相對關係之研究已持續地在進行。然而，要如何修飾其結構，使之能達到最理想的抗菌活性，至今仍未被完全的理解。在改善氟喹啉酮類藥物抗菌能力的部份，尤其是針對如何對抗細菌的抗藥性和抗結核桿菌的研究中，將評估已合成出的氟喹啉酮類化合物在第七位置取代的衍生物。

關鍵字

氟喹諾酮

並列摘要

Recently, emergence of bacterial resistance to most common antimicrobial drugs such as ??ß-lactam antibiotics and macrolides is becoming a serious threat to worldwide public health. Introduction of fluoroquinolones such as norfloxacin and ciprofloxacin provided a valuable weapon against bacteria due to their unique mode of action, inhibition of bacterial DNA gyrase, and their favorable pharmacokinetic and safety profiles. Synthesis of new fluoroquinolones and the evaluation of these agents for antibacterial activity have continued and a series of SAR studies has been performed. However, the structural modification of the fluoroquinolones with respect to their optimum antibacterial activity has not been thoroughly explored. As part of our studies to improve antibacterial potency of fluoroquinolones especially their activities against resistant strains and M. tuberculosis, certain 7-substituted norfloxacin derivatives were synthesized for evaluation.

並列關鍵字

Fluoroquinones

參考文獻

1. Some of more recent revirws include:D. Chu and P. Fernandes, Antimicrob. Agents and Chemotherap., 131 (1989); J. Schentag and J. Domagala, Res. Clin. Forum, 7, 9(1985).

2. Cantwell, M. F.; Snider, D. E., Jr.; Cauthen, G. M.; Onorato, I. M. Epidemiology of Tuberculosis in the United States, 1985-1992. J. Am. Med. Assoc. 1994, 272, 535-539.

3. Cynamom, M. H.; Klemens, S. P.; Chou, T. S.; Gimi, R. H.; Welch, J. T. Antimycobacterial Activity of Series of Pyrazinoic Acid Esters. J. Med. Chem. 1992, 35, 1212-1215.

4. Albrecht, H. A.; Beskid, G.; Chan, K. K.; Christenson, J. G.; Cleeland, R.; Deitcher, K. H.; Georgoopapadakou, N. H.; Keith, D. D.; Pruess, D. L. et. al. Cephalosporin 3’-Quinolone Esters with a Dual Mode of Action. J. Med. Chem. 1990, 33, 77-86.

5. Tetsuo, O.; Teruji, T.; Tadahiko, T.; Kiyoshi, E.; Tadashi, Y.; Shinzo, M. Synthesis and Antibacterial Activities of Novel Oxazine and Thiazine Ring -Fused Tricyclic Quinolonecarboxylic Acids:10-（Alicyclic Amino）-9- Fluoro-7-oxo-7H-pyridol(1,2,3-de)(1,4)benzoxazine-6-carboxylic Acids and the Corresponding 1-Thia Congeners. J. Heterocyclic Chem., 28, 1067（1991）.