Synthesis of N-aryl-2,2,2-trifluoroacetimidoyl piperazinylquinolone derivatives and their antibacterial evaluations Ali Darehkordi a, *, Mahmood Javanmiri a,b , Somayeh Ghazi a,b , Shokrollah Assar b a Department of Chemistry, Faculty of Science, Vali-e-Asr University of Rafsanjan, Rafsanjan 77176, Iran b Department of Microbiolog, Immunology and Biology, Rafsanjan University of Medical Sciences, Rafsanjan, Iran 1. Introduction One particularly important area of medicinal researches is the synthesis and application of organofluorine compounds. Organo- fluorine chemistry has received extensive attention especially in the pharmaceutical industry and in materials science due to the unique properties of fluorinated compounds [1]. Some of the most well known fluorine containing drugs are Prozac 1 (anti-depres- sant), Diflucan 1 (anti-fungal agent), Casodex 1 (anti-cancer agent) and Desflurane (inhalation anesthetic) [1]. Recently, new applica- tion of organofluorine compounds is including their use as potential therapeutics for HIV, cancer or Alzheimer’s disease. Accordingly, the synthesis of these molecules is in great demand [2] and the search for new biologically active fluorinated compounds is in the forefront of organic and medicinal chemistry [3]. Trifluoromethylated imines are particularly important as precursor products or as building blocks for the synthesis of biologically active molecules [4]. A new class of synthetic antibacterial agents is oxazolidinones that have a unique mechanism in inhibition of bacterial protein synthesis [5–9]. The first drug in this class, Zybox (linezolid), has been widely accepted as a valuable addition to the chemotherapeutic arma- mentarium to treat the serious gram-positive bacterial infections [10,11]. The excellent pharmacokinetic properties, high antimi- crobial activities, and few side effects that most quinolones demonstrate explain widespread use of oxazolidinones in clinical practice [12]. These compounds have been effective against gram- negative bacteria, while the gram-positive pathogens, such as Staphylococcus aureus which resist their effects have become a problem [13–19]. Thus, despite many advances in the fluoroquin- olone field, there exists a continuous need for novel quinolones to overcome the limitations of existing drugs. From an SAR viewpoint, antibacterial compounds of both classes feature a heterocyclic amine presented as a popular C-ring in oxazolidinones [5–7] and a mandatory cyclic amine in position 7 of quinolones [20]. In the past few years organofluorine chemistry has returned as an expanding a productive area of research, as can be seen by the increasing number of recent publications, reviews, topics, and monographs [21]. Furthermore, organofluorine chemicals have found a wide range of applications in medicine and agriculture due, in part, to the unique biological properties imparted by the fluorine atom [22]. The 1,4-dihydro-4-oxopyridine-3-carboxylic acids associated with a 5,6-fused aromatic ring is the common chemical feature of bactericidal quinolones (Fig. 1). In the resulting bicyclic ring, the 1-, 5-, 6-, 7-, and 8-positions are the major targets of chemical variation but, synthetic efforts for improved potency the main focus have been on 7-position [23–25]. Both activity spectrum and pharmacokinetic profiles can be controlled at C-7. The most common substituents are cyclic amino Journal of Fluorine Chemistry 132 (2011) 263–268 ARTICLE INFO Article history: Received 9 December 2010 Received in revised form 1 February 2011 Accepted 2 February 2011 Available online 4 March 2011 Keywords: Organofluorine Trifluoroacetimidoyl chloride Piperazinylquinolone Norfloxacin Ciprofloxacin ABSTRACT N-substituted trifluoroacetimidoyl chlorides were used for the synthesis of new piperazinylquinolone derivatives. These reactions provided N-aryl-2,2,2-trifluoroacetimidoyl piperazinylquinolone deriva- tives in good yields. Two selected compounds were evaluated for their antibacterial activities. These compounds displayed good antibacterial activities. ß 2011 Elsevier B.V. All rights reserved. * Corresponding author. Tel.: +98 3913202147; fax: +98 3913202260. E-mail addresses: adarehkordi@yahoo.com, darehkordi@mail.vru.ac.ir (A. Darehkordi). Contents lists available at ScienceDirect Journal of Fluorine Chemistry journal homepage: www.elsevier.com/locate/fluor 0022-1139/$ – see front matter ß 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.jfluchem.2011.02.002