Studies on monocyclic .BETA.-lactam antibiotics. III. Synthesis and antibacterial activity of N-(aromatic heterocyclic substituted)azetidin-2-ones.

Yoshida, Chosaku; Tanaka, Kiyoshi; Nakano, Joji; Todo, Yozo; Yamafuji, T; Hattori, Rikizo; Fukuoka, Yoshikazu; Saikawa, Isamu

doi:10.7164/antibiotics.39.76

Cited by 11 publications

(5 citation statements)

References 4 publications

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“…Compound 145 , consisting of the rewarded (2‐carboxypropan‐2‐yl)oxy group, was highly active against P. aeruginosa (MIC of 0.78 μg/mL). The most potent compound in this series was the fluorine‐incorporating compound 151 with MIC values of ≤0.1 to 0.78 μg/mL against Gram‐negative bacteria, including P. aeruginosa . Compound 151 was later assayed for antibacterial activity against 900 bacterial strains and was found to exhibit highly potent antibacterial activity against Gram‐negative organisms with one to two orders of magnitude lower MIC values when compared to aztreonam 5 (Fig.…”

Section: N1‐aromatic or N1‐heterocyclic Substituted Monocyclic β‐Lactamsmentioning

confidence: 99%

“…β-Lactam C4- bound alkyl substituents resulted in a significant increase in activity against Gram-positive and Gram-negative bacteria. Likewise, the spectrum of activity was strongly dependent on the nature of the oxyimino substituent (R 1 , [181][182][183] Compound 151 was later assayed for antibacterial activity against 900 bacterial strains and was found to exhibit highly potent antibacterial activity against Gram-negative organisms with one to two orders of magnitude lower MIC values when compared to aztreonam 5 (Fig. 3, Table I).…”

Section: N1-aromatic or N1-heterocyclic Substituted Monocyclic β-Lactamsmentioning

confidence: 99%

“…The largest contributions to this research field have been made by Yoshida et al ., who synthesized a library of monocyclic β‐lactams derivatized with an aromatic group or heterocycle on position 1 and with different O ‐substituted 2‐(2‐aminothiazol‐4‐yl)‐2‐oxyiminoacetamido moieties on position 3. The library was assayed against a broad spectrum of microorganisms, and the results as well as their general structures are presented in Table .…”

Section: N1‐aromatic or N1‐heterocyclic Substituted Monocyclic β‐Lactamsmentioning

confidence: 99%

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Antibacterial and β‐Lactamase Inhibitory Activity of Monocyclic β‐Lactams

Decuyper

Jukič

Sosič

et al. 2017

Medicinal Research Reviews

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Due to the widespread emergence of resistant bacterial strains, an urgent need for the development of new antibacterial agents with novel modes of action has emerged. The discovery of naturally occurring monocyclic β-lactams in the late 1970s, mainly active against aerobic Gram-negative bacteria, has introduced a new approach in the design and development of novel antibacterial β-lactam agents. The main goal was the derivatization of the azetidin-2-one core in order to improve their antibacterial potency, broaden their spectrum of activity, and enhance their β-lactamase stability. In that respect, our review covers the updates in the field of monocyclic β-lactam antibiotics during the last three decades, taking into account an extensive collection of references. An overview of the relationships between the structural features of these monocyclic β-lactams, classified according to their N-substituent, and the associated antibacterial or β-lactamase inhibitory activities is provided. The different paragraphs disclose a number of well-established classes of compounds, such as monobactams, monosulfactams, monocarbams, monophosphams, nocardicins, as well as other known representative classes. Moreover, this review draws attention to some less common but, nevertheless, possibly important types of monocyclic β-lactams and concludes by highlighting the recent developments on siderophore-conjugated classes of monocyclic β-lactams.

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Section: N1‐aromatic or N1‐heterocyclic Substituted Monocyclic β‐Lactamsmentioning

confidence: 99%

Section: N1-aromatic or N1-heterocyclic Substituted Monocyclic β-Lactamsmentioning

confidence: 99%

Section: N1‐aromatic or N1‐heterocyclic Substituted Monocyclic β‐Lactamsmentioning

confidence: 99%

See 1 more Smart Citation

Antibacterial and β‐Lactamase Inhibitory Activity of Monocyclic β‐Lactams

Decuyper

Jukič

Sosič

et al. 2017

Medicinal Research Reviews

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“…Samples of 0.1 ml were removed at fixed times and were plated onto drug-free Mueller-Hinton agar after they were suitably diluted. Colonies were counted after incubation at 36°C for 24 h. At the highest concentration of antibiotic (2x the MIC) and for an inoculum of 500 CFU/ml, the drug carryover effects accounted for less than 33% of the cell counts.…”

Section: Methodsmentioning

confidence: 99%

“…These two substituents are responsible for increased antibacterial activity. The synthesis of the racemic form of RU44790 has been reported by Yoshida et al (24).…”

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confidence: 99%

Antibacterial activity of RU44790, a new N-tetrazolyl monocyclic beta-lactam

Chantot¹,

Klich²,

Teutsch³

et al. 1992

Antimicrob Agents Chemother

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RU44790 belongs to a new class of synthetic monocyclic 1-lactam antibiotics which feature a bioisosteric tetrazole moiety instead of the more classical acidic functions at the N-1 position of the 1-lactam ring. Its antibacterial activity was evaluated against some 900 strains and was compared with those of other recent 13-lactam derivatives, especially aztreonam. RU44790 is endowed with potent activity against gram-negative bacteria. At .0.6 ,ug/ml, RU44790 inhibited 90% of all strains of the family Enterobacteriaceae with the exception of Citrobacter spp. (MIC for 90% of strains tested, 1.2 ,ug/ml). The activity was similar to that of aztreonam against strains that are normally susceptible to expanded-spectrum cephalosporins. On the other hand, the new compound was 10 to 100 times more potent than aztreonam and most of the other antibiotics tested against enterobacteria that produce chromosome-encoded or plasmid-mediated extended-spectrum ,-lactamases. Pseudomonas aeruginosa isolates were equally susceptible to both monobactams. RU44790 was inactive against staphylococci and had only marginal activity against streptococci (MIC for 50% of strains tested, 2.5 ,ug/ml). RU44790 was highly resistant to hydrolysis by various 13-lactamases, particularly cephalosporinases such as P99. The latter enzyme was also inhibited by the compound. RU44790 showed a high affinity for penicillin-binding protein 3 ofEscherichia coli. The results suggest that RU44790 has good potential in the treatment of infections caused by gram-negative microorganisms.

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TheMitsunobu Reaction

1992

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Alkyl and aryl phosphites and phosphines react with compounds having weak heteroatom–heteroatom bonds, such as SS, OO, etc., and with azo compounds to form reactive phosphonium salts. These phosphonium salts in turn promote “redox” condensation reactions with compounds having active hydrogens. The condensation reaction of alcohols using the redox couple of a triaryl‐ or trialkylphosphine and a dialkyl azodicarboxylate has become known as the Mitsunobu reaction, based on his pioneering work in the late 1960s. The overall reaction is summarized, wherein the alcohol (R 1 OH) and acidic compound (H–Nu) are condensed to form product (R 1 –Nu), while triphenylphosphine is oxidized to triphenylphosphine oxide and the azodicarboxylate is reduced to the hydrazine. Although the typical redox combination is diethyl azodicarboxylate (DEAD) and triphenylphosphine, many other combinations have found selected use. The reaction is generally limited to primary and secondary alcohols, although tertiary alcohols react in a few intramolecular and intermolecular reactions. For secondary alcohols the reaction usually proceeds with clean inversion of stereochemistry. The acidic component of the reaction generally has an aqueous p K a < 15, with intramolecular reactions providing the exceptions. Examples of H–Nu include oxygen nucleophiles such as carboxylic acids and phenols; nitrogen nucleophiles such as imides, hydroxamates, and heterocycles; sulfur nucleophiles such as thiols and thioamides; and carbon nucleophiles such as β‐ketoesters. Major reviews of the Mitsunobu reaction were published in 1981 by Mitsunobu and in 1983 by Castro. The former review concentrated on reactions using DEAD/triphenylphosphine, while the latter review focused on reactions in which halogens replaced the hydroxy group using reagents such as triphenylphosphine/carbon tetrachloride, triphenyl phosphite/iodomethane, and triphenylphosphine/ N ‐halosuccinimide. Reactions involving the DEAD/triphenylphosphine redox system are the principal subject of this chapter, with emphasis on the literature between 1981 and 1988.

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Studies on monocyclic .BETA.-lactam antibiotics. III. Synthesis and antibacterial activity of N-(aromatic heterocyclic substituted)azetidin-2-ones.

Abstract: The relationship between structure and antibacterial activity among monocyclic i3-lactams having a pyridyl, pyrimidinyl, thiazolyl, imidazolyl, or a tetrazolyl group at N-1 position was investigated. N-(Tetrazol-5-yl)azetidin-2-ones were found to posses excellent activity.

Cited by 11 publications

References 4 publications

Antibacterial and β‐Lactamase Inhibitory Activity of Monocyclic β‐Lactams

Antibacterial and β‐Lactamase Inhibitory Activity of Monocyclic β‐Lactams

Antibacterial activity of RU44790, a new N-tetrazolyl monocyclic beta-lactam

TheMitsunobu Reaction

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