Potent antibacterial agent

A -cyclopropylquinolone 63 and iV-fused pyrrolidinyl 66 and piperidinyl 69 quinolones were reported as intermediates for the preparation of potent antibacterial agents. Use of acids as reaction solvent allow for the cyclization of these iV-substituted... 

As is discussed at a later point in this review, it has been shown that the enantiomer (33) of ofloxacin [81] and the related enantiomer (34) of S-25930 [82] are each significantly more potent antibacterial agents than their respective enantiomers furthermore, the gem-dimethyl analogue (35) is as inactive as the... 

Quinolones possessing a 7-(3-aminopyrrolidin-l-yl) substituent are particularly potent antibacterial agents. However, they often have very low solubility. Based on the observations that the hydroxymethylpyrrolidine (38) is significantly more potent against bacteria than its enantiomer (39) (the hydroxymethyl substituent in (39) apparently has a deleterious effect on activity while the same substituent in (38) has little effect on potency based on comparisons with the unsubstituted pyrrolidine analogue (40)) [84] and the enantiomer (41) is at least as potent as,... 

Sum PE, Lee VJ, Testa RT, Hlavka JJ, Ellestad GA, Bloom JD, Gluzman Y, Tally FP. (1994) Glycylcyclines. 1. Anew generation of potent antibacterial agents through modification of 9-aminotetracyclines. J Med Chem 37 184-188. 

Aminoglycoside resistance has been a powerful impediment to the continued use of these potent antibacterial agents. The myriad of strategies that confer resistance... 

Bronopol (Myacide AS) is a potent antibacterial agent with some activity against yeasts. It was developed originally by the Boots Company in the UK as a preservative for cosmetics and toiletry products and has been used extensively in these areas since the 1970s. More recently it has been adopted in industrial formulation systems due to its low use concentrations and good compatibility... 

Chloramphenicol, thiamphenicol, and florfenicol are broad-spectrum antibacterials with closely related chemical structures (Fig. 3.2). In thiamphenicol, the p-nitro group on the benzene ring of chloramphenicol is replaced with a methyl sulfonyl group. In florfenicol, the hydroxyl group on the side chain of thiamphenicol is replaced with a fluorine. They are all potent antibacterial agents acting... 

This transformation can be applied to 2-methoxycydohexanone. The racemic ketone was hydrogenated with the (S)-XylBINAP/(S,S)-DPEN/Ru catalyst in the presence of a base at 5 °C and under 50 atm of H2 to give (1 R,2S)-2-methoxycy-clohexanol in 99% ee (cis trans=99.5 0.5) (Scheme 12) [37]. This alcohol can be converted to the potent antibacterial agent sanfetrinem after it is oxidized to the chiral ketone. In the same manner, racemic 2-(ferf-butoxycarbonylamino)cyclo hexanone was converted with the (S)-XylBINAP/(R)-DAIPEN/Ru catalyst under basic conditions to the 1S.2R alcohol in 82% ee (cis trans=99 l) [33]. 

The ketoxime derivative fluvoxamine (12) is a newer antidepressant thought to potentiate the action of 5-hydroxytryptamine76. Oxacillin (13), cefuroxime (14) as well as the monobactam aztreonam (15) represent potent antibacterial agents of the beta-lactam type77. The aldoxime pralidoxime (16) and a number of bi.v-quarternary oximes, such as obidoxime (17), can be used as reactivators of the phosphorylated esteratic site of acetylcholinesterase that occurs in the presence of organophosphate inhibitors78,79. 

Da Silva AD, De Almeida MV, De Souza MY Couri MR. Biological activity and synthetic metodologies for the preparation of fluoroquinolones, a class of potent antibacterial agents. CurrMed Chem. 2003 10 21-39. 

Debnath S, Shome A, Das D et al. Hydrogelation through self-assembly of Fmoc-peptide functionalized cationic amphiphiles potent antibacterial agent. J Phys Chem B 114 4407-4415... 

Condensation of 1- and /V(6)-alkyl and unsubstituted 6-aminoindazoles with diethyl ethoxy-methylenemalonate in Dowtherm A at elevated temperature gave the ethyl 6,9-dihydro-9-oxo-pyrazolo[3,4 /]quinoline-8-carboxylates (88) (Equation (49)) <83JHC1351>. The 6-ethyl-8-carboxylic acid derivative is a potent antibacterial agent. 

Aromatic nitro compounds are components of many drugs and other consumer products. For example, nitromide (3,5-dinitrobenzamide) is a potent antibacterial agent, and Ultrasuss (5-nitro-2-propoxyaniline) is 4100 times as sweet as cane sugar. 

R, D. Birkenmeyer and F. Kagan, Lincomycin. XI. Synthesis and structure of clindamycin, a potent antibacterial agent, J. Med. Chem. 13 616 (1970). 

Many Ag(I) compounds are potent antibacterial agents, although the reasons for this are not well understood. Silver sulfadiazine (15) is... 

SAR studies were performed on compoimds containing the 9H-isothia-zolo[5,4-fc]quinoline-3,4-dione (ITQ) nucleus and it was found that some of them are potent antibacterial agents (see Scheme 101) [114,115]. They were prepared from compound 353, which was treated with cyclopropyl isothiocyanate in DMF and then with Mel. Compound 354 (94%) was obtained and treated with in NaH in DMF to give the isothiazolo[ 5,4-fo] quinoline compound 355 (93%). Its treatment with anhydrous NaSH gave the corresponding mercaptan (84%), which was directly cychsed without purification to 356 (85%) in the presence of hydroxylamine-O-sulfonic acid. Microwave-assisted Suzuki-Miyaura cross-coupling of the ITQ nucleus 356 with the desired aryl-boronic esters or acids afforded derivatives 357, typically, in 30-50% yield after HPLC purification (Scheme 87). 

NIS is used as a selective M-demethylating agent under mild conditions. These conditions have been successfully applied to the synthesis of metabolites of potent antibacterial agents within the macrolide and ketoUde classes (eq 23). ... 

Modification of the groups which occupy the N-1, C-5, C-7 and C-8 positions has been successful in yielding potent antibacterial agents. 

Because fosmidomycin and FR900098 are also potent antibacterial agents, a prodrug approach has been examined to determine whether it would increase... 

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