925457-08-5

Upstream product

• 722542-90-7 (Z)-3-Diethylamino-2-(2,4,5-trifluoro-3-methoxy-benzoyl)-acrylic acid ethyl ester 
• 146726-08-1 (1α,5α,6α)-6-tert-butoxycarbonylamino-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid benzyl ester 
• 134575-15-8 (1α,5α,6α)-3-(benzyloxycarbonyl)-3-azabicyclo[3.1.0]hexane-6-carboxylic acid 
• 134575-06-7 ethyl (1α,5α,6α)-3-benzyl-3-azabicyclo[3.1.0]hexane-2,4-dione-6-carboxylate 
• 134575-14-7 benzyl (1α,5α,6α)-6-hydroxymethyl-3-azabicyclo[3.1.0]hexan-3-ylcarboxylate 
• 134575-07-8 (1α,5α,6α)-6-hydroxymethyl-3-benzyl-3-aza-bicyclo[3.1.0]hexane 
• 134575-13-6 (1α,5α,6α)-6-(hydroxymethyl)-3-azabicyclo[3.1.0]hexane 
• 367-25-9 2,4-difluorophenylamine 
• 114214-48-1 ethyl 1-(2,4-difluorophenyl)-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinoline-carboxylate 
• 112811-66-2 2,4,5-trifluoro-3-methoxybenzoyl chloride 
• 112811-65-1 3-methoxy-2,4,5-trifluorobenzoic acid 
• 134575-17-0 tert-butyl (1R,5S,6R)-3-azabicyclo[3.1.0]hexan-6-ylcarbamate 

Relevant academic research and scientific papers

Design, synthesis and activity against Toxoplasma gondii, Plasmodium spp., and Mycobacterium tuberculosis of new 6-fluoroquinolones

This paper reports on the rational design of a series of new 6-fluoroquinolones by QSAR analysis against Toxoplasma (T.) gondii, their synthesis, their biological evaluation against T. gondii and Plasmodium (P.) spp., and their effect on Mycobacterium (M.) tuberculosis DNA gyrase and growth inhibition. Of the 12 computer-designed 8-ethyl(or methoxy)- and 5-ethyl-8-methoxy-6-fluoroquinolones predicted to be active against T. gondii, we succeeded in the synthesis of four 6-fluoro-8-methoxy-quinolones. The four 6-fluoro-8-methoxy-quinolones are active on T. gondii but only one is as active as predicted. One of these four compounds appears to be an antiparasitical drug of great potential with inhibitory activities comparable to or higher than that of trovafloxacin, gatifloxacin, and moxifloxacin. They also inhibit DNA supercoiling by M. tuberculosis gyrase with an efficiency comparable to that of the most active quinolones but are poor inhibitors of M. tuberculosis growth.

Synthesis of new fluoroquinolones and evaluation of their in vitro activity on Toxoplasma gondii and Plasmodium spp.

The synthesis of four new computer-designed fluoroquinolones which have been predicted by QSAR analysis to be active against the protozoa Toxoplasma gondii is described. These compounds are inhibitory in vitro for T. gondii. One of these compounds has a remarkably high activity comparable to that of trovafloxacin. It combines the basic cyclopropyl-quinoline structure of gatifloxacin or moxifloxacin with the C-7 6-amino-3-azabicyclo[3.1.0]hexyl side chain of trovafloxacin. The four compounds are also inhibitory for blood stages of Plasmodium falciparum though at high concentration. These results confirm the potential of quinolones as anti-T. gondii and antimalarial drugs but also show that the QSAR models for T. gondii cannot be reliably extended for screening antimalarial activity.