synthesis and antibacterial activities of optically active ofloxacin and its fluoromethyl derivative.

Atarashi, Shohgo; Yokohama, Shuichi; Yamazaki, Katuo; Sakano, Katsu-ichi; Imamura, Masako; Hayakawa, Isao

doi:10.1248/cpb.35.1896

Cited by 115 publications

(45 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…35) The minimum inhibitory concentrations (MICs) of the synthesized compounds 7a-f, 8, and 11a, f against several representative Gram-positive and Gram-negative bacteria utilizing a conventional agar dilution procedure 36) are listed in Table 5, along with the data for levofloxacin (LVFX) for comparison. 37,38) The compounds 7a-f bearing 3-sulfenylazetidines as the C7 substituent of 6 exhibited moderate antibacterial activities against each species of bacteria. The antibacterial activities (except for those against Escherichia coli) of 7a, b and 7e are somewhat potent among the 7-(3-sulfenylazetidin-1-yl)fluoroquinolone series compounds 7a-f.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of New Quinolone Antibiotics Utilizing Azetidine Derivatives Obtained from 1-Azabicyclo[1.1.0]butane

Ikee

Hashimoto

Kamino

et al. 2008

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

Although 1-azabicyclo[1.1.0]butane (ABB, 3) proved to be the unique molecule bearing the highly strained bicyclic structure, little attention has been paid to the unusual ring system. [1][2][3][4][5][6][7][8][9][10] Specifically, the synthetic utility of ABB (3), which must be useful for the preparation of various 1,3-disubstituted and 3-monosubstituted azetidines, 1,9,10) has scarcely reported because of its synthetic difficulty due to the remarkably strained structure. These azetidine moieties have often been found in many natural products 11) and biologically active compounds such as carbapenems 1) and new quinolone antibiotics.12-15) 1,3,3-Trinitroazetidine (TNAZ), 16,17) an insensitive high explosive, was also synthesized by using ABB (3). In recent years, we established an efficient method for synthesis of ABB (3) starting from allylamine (1) via 2,3-dibromopropylamine hydrobromide (2), and reported its application to the synthesis of several azetidine derivatives, as shown in Chart 1. 9) We also reported a practical synthesis of 1-(1,3-thiazolin-2-yl)azetidine-3-thiol as the fascinating pendant moiety of a new oral 1b-methylcarbapenem antibiotic, L-084 by starting from ABB (3).1) This expeditious construction method for 3-monosubstituted azetidine derivatives employing ABB (3) seemed to be useful also for developing new quinolone antibiotics.Fluoroquinolones have been developed and are widely used clinically. This is because they have potent, a broad spectrum of antibacterial activities, and few side effects. [18][19][20][21][22] However, increasingly multidrug-resistant pathogens, especially methicillin-resistant Staphylococcus aureus (MRSA), have become a serious problem particularly during the last decade.23) The resistance levels to quinolones are as yet relatively low but are steadily increasing.24) Therefore new antibacterial agents have become increasingly urgent. This prompted us to develop new quinolones utilizing the azetidine derivatives, in which the C7 substituents of fluoroquinolone carboxylic acids play important antibacterial roles.18-22) Previously, we communicated synthesis and antibacterial activities of new quinolone derivatives utilizing ABB (3). 10)We now describe, in detail, a convenient method of synthesizing several 3-sulfenyl-and 3-aminoazetidine derivatives utilizing ABB (3), and we discuss the synthesis and antibacterial activities of new quinolone antibiotics incorporating these azetidine derivatives to the C7 position. Although several examples of 7-azetidinylquinolones have been reported, [12][13][14][15] there have been not many prominent quinolone antibiotics bearing the azetidinyl substituent groups thus far. We envisaged that the introduction of azetidine derivatives onto the C7 position of the quinolone nucleus might enhance their antibacterial activities against MRSA. Results and DiscussionA tetrahydrofuran (THF) solution of ABB (3), obtained by treatment of 2,3-dibromopropylamine hydrobromide (2) with n-BuLi at Ϫ78°C in THF followed by codistillation with THF, 1) was...

show abstract

Section: Resultsmentioning

confidence: 99%

Synthesis of New Quinolone Antibiotics Utilizing Azetidine Derivatives Obtained from 1-Azabicyclo[1.1.0]butane

Ikee

Hashimoto

Kamino

et al. 2008

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

show abstract

“…Reaction of N-desmethyl levofloxacin 5 with 2-chloro-5-(nitroaryl)-1,3,4-thiadiazole 6a -f in ethanol in the presence of NaHCO 3 at reflux temperature gave compounds 4a -f [5]. The intermediate N-desmethyl levofloxacin 5 was prepared according to the known method [8], by the reaction of piperazine with ( -)-9,10-difluoro-2,3-dihydro-3-methyl-7-oxo-7H-pyrido[1,2,3-de] [1,4]benzoxazine-6-carboxylic acid. The requisite 2-chloro-5-(nitroaryl)-1,3,4-thiadiazole 6a -f was prepared according to the previously described methods [5 -7, 9].…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Antibacterial Activity of Nitroaryl Thiadiazole‐Levofloxacin Hybrids

Foroumadi¹,

Mansouri

Emami

et al. 2006

Archiv der Pharmazie

View full text Add to dashboard Cite

Novel levofloxacin-containing hybrids carrying a 5-(nitroaryl)-1,3,4-thiadiazol-2-yl group were synthesized and evaluated in vitro against Gram-positive and Gram-negative bacteria. Preliminary data indicated that levofloxacin-nitrofuran and levofloxacin-nitroimidazole hybrids have a potent activity against Gram-positive organisms with enhanced anti-staphylococcal activity compared with the parent quinolone (N-desmethyl levofloxacin).

show abstract

“…The S-enantiomer being between 8-to 128-fold more active against both Grampositive and Gram-negative bacteria than the Rantipode 16 .…”

Section: Ofloxacinmentioning

confidence: 95%

“…carbenicillin, in the case of others there are potential advantages with the use of single isomers, e.g. ofloxacin 16,17,18 However, in the case of latamoxef, a compound which undergoes in-vivo epimerization with a half-life similar to its apparent serum elimination half-life the situation is by-no-means clear cut. These agents emphasise the importance of considering each compound individually, i.e.…”

Section: Stereochemistry and Its Role In Drug Designmentioning

confidence: 99%

Untitled

2014

IJPSR

View full text Add to dashboard Cite

When designing small molecules to interact with the targets, one should consider stereo selectivity. As considerations for exploring structure space evolve, chirality is increasingly important. Binding affinity for a chiral drug can differ for diastereomers and between enantiomers. For the virtual screening and computational design stage of drug development, this problem can be compounded by incomplete stereochemical information in structure libraries leading to a "coin toss" as to whether or not the "ideal" chiral structure is present. Creating every stereoisomer for each chiral compound in a structure library leads to an exponential increase in the number of structures resulting in potentially unmanageable file sizes and screening times. Therefore, only key chiral structures, enantiomeric pairs based on relative stereochemistry need be included, and lead to a compromise between exploration of chemical space and maintaining manageable libraries. In clinical environments, enantiomers of chiral drugs can have reduced, no, or even deleterious effects. This underscores the need to avoid mixtures of compounds and focus on chiral synthesis. Governmental regulations emphasizing the need to monitor chirality in drug development have increased. The United States Food and Drug Administration issued guidelines and policies in 1992 concerning the development of chiral compounds. These guidelines require that absolute stereochemistry be known for compounds with chiral centers and that this information should be established early in drug development in order that the analysis can be considered valid. From exploration of structure space to governmental regulations it is clear that the question of chirality in drug design is of vital importance.

show abstract

synthesis and antibacterial activities of optically active ofloxacin and its fluoromethyl derivative.

Cited by 115 publications

References 2 publications

Synthesis of New Quinolone Antibiotics Utilizing Azetidine Derivatives Obtained from 1-Azabicyclo[1.1.0]butane

Synthesis of New Quinolone Antibiotics Utilizing Azetidine Derivatives Obtained from 1-Azabicyclo[1.1.0]butane

Synthesis and Antibacterial Activity of Nitroaryl Thiadiazole‐Levofloxacin Hybrids

Untitled

Contact Info

Product

Resources

About