- CEPHALOSPORIN CIPROFLOXACIN HYBRID COMPOUNDS
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A compound of formula (Ia) and related aspects.
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Page/Page column 34; 40
(2020/06/05)
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- PRODRUG INHIBITORS
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Provided herein are compounds useful as metallo-β-lactamase (MBL) inhibitors. The compounds have a formula A–B, where A is a β-lactam antibiotic moiety comprising a bridging methylene (-CH2-) covalently attached to -B; and B is a latent MBL inhibitor. Also provided are formulations comprising such compounds; as well as such compounds or formulations for use as a medicament. The compounds and formulations may be used in the treatment of antibiotic resistance, bacterial infection. The compounds and formulations may be used in the inhibition of a bacterial MBL.
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Paragraph 00123
(2020/10/20)
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- Exploitation of Antibiotic Resistance as a Novel Drug Target: Development of a β-Lactamase-Activated Antibacterial Prodrug
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Expression of β-lactamase is the single most prevalent determinant of antibiotic resistance, rendering bacteria resistant to β-lactam antibiotics. In this article, we describe the development of an antibiotic prodrug that combines ciprofloxacin with a β-lactamase-cleavable motif. The prodrug is only bactericidal after activation by β-lactamase. Bactericidal activity comparable to ciprofloxacin is demonstrated against clinically relevant E. coli isolates expressing diverse β-lactamases; bactericidal activity was not observed in strains without β-lactamase. These findings demonstrate that it is possible to exploit antibiotic resistance to selectively target β-lactamase-producing bacteria using our prodrug approach, without adversely affecting bacteria that do not produce β-lactamase. This paves the way for selective targeting of drug-resistant pathogens without disrupting or selecting for resistance within the microbiota, reducing the rate of secondary infections and subsequent antibiotic use.
- Evans, Lindsay E.,Krishna, Aishwarya,Ma, Yajing,Webb, Thomas E.,Marshall, Dominic C.,Tooke, Catherine L.,Spencer, James,Clarke, Thomas B.,Armstrong, Alan,Edwards, Andrew M.
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p. 4411 - 4425
(2019/05/17)
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- Studies at the ionizable position of cephalosporins and penicillins: Hydroxamates as substitutes for the traditional carboxylate group
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Classically, β-lactams need an ionizable group to potentiate antibacterial activity. Sets of cephalosporins and penicillins featuring different substituted hydroxamates in place of the traditional carboxylate group have been synthesized and tested for antibiotic activity. Many of the compounds exhibited anti-bacterial activities with notable MIC values in the range of 6-0.2 μM.
- Majewski, Mark W.,Miller, Patricia A.,Miller, Marvin J.
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p. 292 - 296
(2017/03/10)
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- β-LACTAMASE TARGETED PHOTOSENSITIZER FOR PESTICIDE AND PEST DETECTION
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Photoactivatable pesticide compounds and methods for the use thereof in the elimination and detection of pests are provided.
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Page/Page column 64
(2014/01/09)
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- CEPHALOSPORIN DERIVATIVES USEFUL AS β-LACTAMASE INHIBITORS AND COMPOSITIONS AND METHODS OF USE THEREOF
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The present invention relates to cephalosporin derivatives having β- lactamase inhibitory activity. The compounds are useful in preventing or treating bacterial resistance to an antibiotic, e.g. a β-lactam antibiotic. Disclosed herein are compounds that are inhibitors of class B metallo-β-lactamases, as well as class A, C, and D serine β-lactamases. In some preferred embodiments, the compounds are 3'- thiobenzoate derivatives of a cephalosporin. Pharmaceutical compositions, methods, uses, kits and commercial packages comprising the compounds are also disclosed.
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Page/Page column 53-54
(2011/09/21)
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- PHOTOACTIVATABLE ANTIMICROBIAL AGENTS AND THERAPEUTIC AND DIAGNOSTIC METHODS OF USING SAME
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The present invention provides photosensitizer compounds for use in detecting beta-lactamase activity. Methods and kits that utilize the photosensitizer compounds of the invention for the detection of, quantitation of, and classification or typing of microbial beta-lactamases.
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Page/Page column 33
(2011/05/16)
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- Enzymatic deprotection of the cephalosporin 3′-acetoxy group using Candida antarctica lipase B
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(Chemical Equation Presented) Cephalosporins remain one of themost important classes of antibiotics. A useful site for derivatization involves generation of and chemistry at the 3′-hydroxymethyl position. While 3′-acetoxymethyl-substituted cephalosporins are readily available, deacetylation to access the free 30-hydroxymethyl group is problematic when the carboxylic acid is protected as an ester. Herein we report that this important transformation has been efficiently accomplished using Candida antarctica lipase B. Although this transformation is difficult to carry out using chemical methods, the enzymatic deacetylation has been successful on gram scale, when the cephalosporin is protected as either the benzhydryl or tert-butyl esters and on the corresponding sulfoxide and sulfone of the tert-butyl ester.
- Patterson, Leslie D.,Miller, Marvin J.
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supporting information; experimental part
p. 1289 - 1292
(2010/04/29)
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- An improved process for the preparation of diphenylmethyl7β- Phenylacetamido-3-hydroxymethyl-3-cephem-4-carboxylate
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An efficient and improved process for the preparation of diphenylmethyl 7-phenylacetamido-3-hydroxymethyl-3-cephem-4-carboxylate was developed. With the commercially available 7-aminocephalosporanic acid (7-ACA) as starting material, up to 73.5% overall isolated yield of the titled compound was synthesized in two steps via direct phenylacetylation with phenylacetyl chloride, followed by basic hydrolysis and esterification with diphenyldiazomethane. The newly developed process obviated the use of protecting groups, reduced the environmental footprint, and could be easily controlled and conveniently scaled up for this pivotal intermediate in cephalosporin chemistry.
- Keping, Yu,Nan, Sun,Shanzong, Fang,Weimin, Mo,Baoxiang, Hu,Zhenlu, Shen,Xinquan, Hu
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experimental part
p. 815 - 819
(2010/04/22)
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- PHOTOACTIVATABLE ANTIMICROBIAL AGENTS
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Photoactivatable antimicrobial compounds and methods for the use thereof in the treatment of infections are provided.
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Page/Page column 41-42
(2008/06/13)
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- A new convenient synthesis of 3-carboxycephems starting from 7-aminocephalosporanic acid (7-ACA)
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New convenient syntheses of 3-carboxycephems starting from 7-ACA are reported. All three possible cephem derivatives with respect to the position of the double bond in the six-membered ring and oxidation state of the sulfur atom have been synthesized in high overall yield.
- Keltjens, Rolf,Vadivel, Subramanian K.,De Vroom, Erik,Klunder, Antonius J. H.,Zwanenburg, Binne
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p. 2529 - 2534
(2007/10/03)
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- A facile removal of p-methoxybenzyl and diphenylmethyl ester with iodotrimethyl-silane-triphenylphosphine
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Diphenylmethyl (DPM) and p-methoxybenzyl (PMB) ester of cephalosporin derivatives were converted to the corresponding carboxylic acid using iodotrimethylsilane (TMSI)-triphenylphosphine (TPP) in dichloromethane at room temperature in good yields.
- Cha, Kyung Hoi,Kang, Tae Won,Cho, Dong Ock,Lee, Hong-Woo,Shin, Jaewook,Jin, Kyung Yong,Kim, Kyung-Whan,Kim, Jung-Woo,Hong, Chung-Il
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p. 3533 - 3540
(2007/10/03)
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- MILD PALLADIUM(0)-CATALYZED DEPROTECTION OF ALLYL ESTERS. A USEFUL APPLICATION IN THE SYNTHESIS OF CARBAPENEMS AND OTHER β-LACTAM DERIVATIVES.
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Carbapenem and other β-lactam allyl ester derivatives are efficiently deprotected with pyrrolidine in the presence of catalytic amount of Pd(0).
- Deziel, Robert
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p. 4371 - 4372
(2007/10/02)
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- Polymer-bound carbonic anhydrides in N-acylation of 7-aminocephalosporanic acid.
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Aminocephalosporanic acid tert-butyl ester was reacted with polystyrene-bound mixed carbonic-carboxylic anhydrides to give the corresponding N-acylated derivatives. Clevage of the tert-butyl protecting group with trifluoroacetic acid gave the corresponding cephalosporanic acid.
- Martin,Shambhu,Digenis
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p. 110 - 111
(2007/10/09)
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