Design, Synthesis, and Antimicrobial Activity of 6-O-Substituted Ketolides Active against Resistant Respiratory Tract Pathogens

Or, Yat Sun; Clark, Richard F.; Wang, Sanyi; Chu, Daniel T. W.; Nilius, Angela M.; Flamm, Robert K.; Mitten, Michael J.; Ewing, Patty J.; Alder, Jeff; Ma, Zhenkun

doi:10.1021/jm990618n

Cited by 109 publications

(36 citation statements)

References 23 publications

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“…Interestingly, for solithromycin, weak binding to ribosomes dimethylated at A2058Ec could be detected by chemical probing 71. Key structural features of the ketolides are summarized in Figure 13 (for an example of a ketolide with a 6‐ O ‐attached side chain, see cethromycin) 74, 75…”

Section: Protein Synthesis Inhibitorsmentioning

confidence: 99%

Targeting Antibiotic Resistance

2016

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Finding strategies against the development of antibiotic resistance is a major global challenge for the life sciences community and for public health. The past decades have seen a dramatic worldwide increase in human‐pathogenic bacteria that are resistant to one or multiple antibiotics. More and more infections caused by resistant microorganisms fail to respond to conventional treatment, and in some cases, even last‐resort antibiotics have lost their power. In addition, industry pipelines for the development of novel antibiotics have run dry over the past decades. A recent world health day by the World Health Organization titled “Combat drug resistance: no action today means no cure tomorrow” triggered an increase in research activity, and several promising strategies have been developed to restore treatment options against infections by resistant bacterial pathogens.

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Section: Protein Synthesis Inhibitorsmentioning

confidence: 99%

Targeting Antibiotic Resistance

2016

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“…1 Recently, 3-keto derivatives of clarithromycin, termed ketolides, have been developed to combat the growing prevalence of MLS B resistance. 2 Ketolides, the third-generation erythromycin derivatives, are represented by telithromycin (HMR3647), 3 cethromycin (ABT-773) 4 and TE-802 5 (Figure 1). …”

Section: Introductionmentioning

confidence: 99%

Synthesis and antibacterial activity of 2, 3-dehydro-3-O-(3-aryl-E-prop-2-enyl)-10, 11-anhydroclarithromycin derivatives

et al. 2011

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An allyl group was attached to 3-keto function of ketolides in the presence of allyl bromide and KOtBu. Consequently, the Heck reaction of the resulting 2, 3-dehydro-3-O-allyl-10, 11-anhydroclarithromycin derivatives, in the presence of palladium (II) acetate and tri(o-tolyl)phosphine, afforded a 3-O-(3-aryl-E-prop-2-enyl) sidechain, not the previously reported 3-O-(3-aryl-Z-prop-1-enyl) sidechain. The results suggested that some steric factors in b-hydrogen elimination might regulate the isomerization. The activity of 2, 3-dehydro-3-O-(3-aryl-E-prop-2-enyl)-10, 11-anhydroclarithromycin derivatives was low.

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“…[5][6][7] To overcome the growing problems of macrolide resistance, great efforts have been made to discover novel macrolides. The kelolides, including telithromycin ( Figure 1) and cethromycin (ABT-773), [8][9][10][11][12] which displayed improved activities against macrolide-resistant pathogens such as Streptococcus pneumoniae (S. pneumoniae) and Staphylococcus aureus (S. aureus), were developed. Both telithromycin and cethromycin share the same key structure features, including 3-keto group, 11,12-cyclic carbamate and a proper hetero-arylalkyl side chain, which is responsible for binding to the 23S ribosomal RNA of bacteria.…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis and antibacterial activity of novel ketolides bearing an aryltetrazolyl-substituted alkyl side chain

et al. 2011

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A set of 17 novel ketolides bearing an aryltetrazolyl-substituted alkyl side chain were synthesized and evaluated for their antibacterial activities, which the aryltetrazolyl group was selected to replace the hetero-aryl moiety of the side chain in telithromycin for designing new compounds. The synthesis of aryltetrazolyl alkylamines was reported in detail. The antibacterial activities of new ketolides were evaluated against a number of pathogens including macrolide-resistant organisms by using telithromycin as the reference. Many of the evaluated compounds exhibited remarkable activities against both erythromycinsusceptible and erythromycin-resistant organisms such as Staphylococcus aureus (except S. aureus AD-08), Pseudomonas aeruginosa and Escherichia coli. Among these, the compound 11e exhibited excellent antibacterial potency against all the strains in comparison with others.

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Design, Synthesis, and Antimicrobial Activity of 6-O-Substituted Ketolides Active against Resistant Respiratory Tract Pathogens

Cited by 109 publications

References 23 publications

Targeting Antibiotic Resistance

Targeting Antibiotic Resistance

Synthesis and antibacterial activity of 2, 3-dehydro-3-O-(3-aryl-E-prop-2-enyl)-10, 11-anhydroclarithromycin derivatives

Design, synthesis and antibacterial activity of novel ketolides bearing an aryltetrazolyl-substituted alkyl side chain

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