Pyridine antibacterial activity

Extensive investigations have been performed related to the synthesis of new adamantane derivatives with better therapeutic actions and less adverse effects. For example, it has been proved that adamantylamino-pyrimidines and -pyridines are strong stimulants of mmor necrosis factor-a (TNF-a) [132]. TNF is a substance that can improve the body s namral response to cancer by killing cancer cells. Another example is 1,6-diaminodiamantane [87], which possesses an antitumor and antibacterial activity. Also, many derivatives of aminoadamantanes have antiviral activity like 3-(2-adamantyl) pyrolidines with two pharmacophoric amine groups, which have antiviral activity against influenza-A virus [133]. 

Among the few reported inhibitors, the optimized HTS lead phe-nylimidazole 39 is an interesting candidate against S. pneumoniae with nanomolar FabK inhibition and an MIC90 of 4 pg/mL [59]. The same team hybridized 29, a FabI pyridine inhibitor with 39 to provide 40, in an attempt to realize a compound with a dual mode of action. Although inhibition of both enzymes as well as sub-pg/ mL MIC against S. pneumoniae is retained, the Fabl-related antibacterial activity against S. aureus is lost [60]. 

The synthesis of the representative compound of this series, 1,4-dihydro-l-ethyl-6-fluoro (or 6-H)-4-oxo-7-(piperazin-l-yl)thieno[2/,3/ 4,5]thieno[3,2-b]pyridine-3-carboxylic acid (81), follows the same procedure as that utilized for compound 76. Namely, the 3-thienylacrylic acid (77) reacts with thionyl chloride to form the thieno Sjthiophene -carboxyl chloride (78). Reaction of this compound with monomethyl malonate and n-butyllithium gives rise to the acetoacetate derivative (79). Transformation of compound 79 to the thieno[2 3f 4,5]thieno[3,2-b]pyhdone-3-carboxy ic acid derivative (80) proceeds in three steps in the same manner as that shown for compound 75 in Scheme 15. Complexation of compound 75 with boron trifluoride etherate, followed by reaction with piperazine and decomplexation, results in the formation of the target compound (81), as shown in Scheme 16. The 6-desfluoro derivative of 81 does not show antibacterial activity in vitro. 

Further development in the chemistry of oxazolidinone antibacterials was based mainly on the assumption that the 4-pyridyl moiety of one of Dupont s lead compounds, E-3709, might be amenable to replacement by suitably saturated heterocyclic bioisosteres [48]. This assumption was based on an example in which successful replacement of the piperazine ring system in the quinolone antibacterials, such as ciprofloxacin, with a pyridine fragment, such as seen in Win-57273, results in improvement of both the antibacterial and the pharmacokinetic profiles of the compounds. Similarly, as in the case of ciprofloxacin and Win-57273, it was predicted that the presence of a small but highly electron-withdrawing fluorine atom would be tolerated at the meta position(s) of the central phenyl ring, and would confer enhanced antibacterial activity and/or other desirable properties to the targeted oxazolidinones, as shown in Fig. 3. 

The coordination shell comprises three fac-S and three fac-N-donor atoms in [Fe(6mp)3] [FeClJCl, where 6mp = 6-thiopurine, (189). Both iron(II) and iron(III) complexes are included in a review of transition metal complexes of thiosemicarbazones. " 5,5 -Dimethyl-l,2,3-cyclohex-anetrione-l,2-dioxime-3-thiosemi-carbazone, dcdt (190), acts as an A, A, 5 -donor to Fe +, giving a bis-ligand complex (contrast [Fe(7V,7V -dcdt)3] with Fe " "). The Schiff bases from pyridine 2-carboxaldehyde and thiosemicarbazide or 4-phenyl thiosemicarbazide also act as A, VV, 5 -donors, both to Fe " " and to Fe " ". The antibacterial activity of these complexes was assessed, in... 

Sulfasalazine is a prodrug of which 70% is converted by colon bacteria to two active metabolites, sulfapyri-dine and 5-aminosalicylic acid (mesalamine). Sulfa-pyridine has antibacterial activities, and 5-aminosali-... 

The Influence of Chemical Constitution on Antibacterial Activity. Part IV. A Survey of Heterocyclic Bases with special reference to Benzoquinolines, Phenanthri-dines, Benzacridines, Quinolines and Pyridines. 

Thiophen Analogues of Quinoline.—Cyclization of (96) by treatment with AICI3 gave 4-amino-5-cyanothieno[2,3-/)]pyridines. 4-(Acylamino)thieno[2,3-f7]-pyridines were obtained from (186). 4-Amino-5-cyanothieno[2,3-Z>]pyridones were synthesized from 2-amino-3-cyanothiophens and ethyl cyanoacetate in the presence of sodium ethoxide. These compounds showed antibacterial activity. Through the reaction of 2-chloro-3-cyano-pyridines with ethyl thioglycollate followed by base-catalysed ring-closure, 3-aminothieno[2,3-6]pyridines were prepared, and these were transformed into various derivatives, including tricyclic systems. ... 

Gao and co-workers investigated the random copolymers of acrylamide and vinyl pyridine, of varying MW and pyridine content, which were subsequently quaternised with dimethyl sulfate [22], Investigations proved that polymers with higher cationic functionality showed stronger antibacterial activity. In addition, depending on their alkyl chain length, methacrylate-based polymers with pendent pyridinium moieties were found to exhibit antibacterial activity [23]. 

Quaternary pyridinium polymers can show biological activity when bound to surfaces, e.g., poly(4-vinyl pyridine)-modified glass surfaces which were modified using different alkyl bromide derivatives. Suitable polymers for antibacterial applications not only exhibit antibacterial activity, but also non-toxicity to human cells (i.e., selectivity). 

Simple substituted pyridines such as isoniazid (7) showed antibacterial activity. The structurally related ethionamide (8) is an active antibiotic prodrug against tuberculosis in humans. Nicotine (1) and epibatidine (9) are naturally occurring agonists of neural nicotinic acetylcholine receptors... 

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