Reactivity and selectivity in the inhibition of elastase by 3-oxo-β-sultams and in their hydrolysis

Tsang, Wing Y.; Ahmed, Naveed; Hemming, K.; Page, Michael I.

doi:10.1039/b713899g

Cited by 24 publications

(18 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In related work, bicyclic lactam derived 'trans-lactam' inhibitors, ultimately derived from more complex natural products, were developed as potent inhibitors of nucleophilic serine proteases [101][102][103][104] (though these have not been d eveloped as PBP/serine β-lactamase inhibitors).…”

Section: Future Science Groupmentioning

confidence: 99%

The Road to Avibactam: The First Clinically Useful Non-β-Lactam Working Somewhat Like a β-Lactam

et al. 2016

View full text Add to dashboard Cite

Avibactam, which is the first non-β-lactam β-lactamase inhibitor to be introduced for clinical use, is a broad-spectrum serine β-lactamase inhibitor with activity against class A, class C, and, some, class D β-lactamases. We provide an overview of efforts, which extend to the period soon after the discovery of the penicillins, to develop clinically useful non-β-lactam compounds as antibacterials, and, subsequently, penicillin-binding protein and β-lactamase inhibitors. Like the β-lactam inhibitors, avibactam works via a mechanism involving covalent modification of a catalytically important nucleophilic serine residue. However, unlike the β-lactam inhibitors, avibactam reacts reversibly with its β-lactamase targets. We discuss chemical factors that may account for the apparently special nature of β-lactams and related compounds as antibacterials and β-lactamase inhibitors, including with respect to resistance. Avenues for future research including non-β-lactam antibacterials acting similarly to β-lactams are discussed.

show abstract

Section: Future Science Groupmentioning

confidence: 99%

The Road to Avibactam: The First Clinically Useful Non-β-Lactam Working Somewhat Like a β-Lactam

et al. 2016

View full text Add to dashboard Cite

show abstract

“…These observations indicate a concerted mechanism with simultaneous bond formation and fission (12) in which the amide leaving group is expelled as an anion (13). The sensitivity of the Brønsted b nuc and b lg values to the nucleofugality of the amide leaving group and the nucleophilicity of the amine nucleophiles, respectively, indicate a coupled bond formation and bond fission processes [125]. …”

Section: Aminolysismentioning

confidence: 90%

Structure and Reactivity of β‐Lactams

Page

2010

Amino Acids, Peptides and Proteins in Organic Chemistry

Self Cite

View full text Add to dashboard Cite

“…Exceptionally, the thiolysis of some cephalosporins appears to involve the breakdown of the tetrahedral intermediate by the expulsion of an enamine anion [211]. Unlike the strongly base catalyzed aminolysis of b-lactam antiobiotics, such as penicillins and cephaloridines, the rate law for the aminolysis of N-aroyl b-lactams is dominated by a term with a first-order dependence on amine concentration in its free base form, which is indicative of an uncatalyzed aminolysis reaction that proceeded by a concerted mechanism [212]. The relative sequence of bond making and breaking between heavy atoms in the aminolysis of b-lactam antibiotics is a result of subtle effects that often involve proton transfer.…”

Section: Alcoholysis Thiolysis and Aminolysismentioning

confidence: 96%

The Chemistry of 2‐Azetidinones (β‐Lactams)

Alcaide¹,

Almendros²,

Luna³

2011

Modern Heterocyclic Chemistry

View full text Add to dashboard Cite

The large number of recent reports on b-lactam chemistry demonstrates the increasing interest in this important class of compounds. Monocyclic b-lactams frequently serve as precursors for the synthesis of classical bicyclic b-lactam antibiotics. The cyclic 2-azetidinone skeleton has been extensively used as a template on which to build the heterocyclic structure fused to the four-membered ring, using the chirality and functionalization of the b-lactam nucleus as a stereocontrolling element. The discovery of nonclassical b-lactam antibiotics, such as monobactams and nocardicins, coupled with ever-growing new applications such as enzyme inhibition has triggered a renewed interest in the building of new monocyclic b-lactam derivatives. Besides the utility of b-lactams as biologically active agents, they are used as intermediates in a-and b-amino acid synthesis, as well as building blocks for alkaloids, heterocycles, taxoids and other types of compounds of biological and medicinal interest. Physicochemical Data Computational ChemistryTheoretical studies show that b-lactams are weaker bases, in the gas phase, than acyclic amides [1]. The attenuation of basicity upon cyclization is stronger than that found for cyclic ketones of similar size due to the existence of a negative hyperconjugation effect that is present in b-lactams but not in cyclic ketones. Ab initio calculations indicate that both b-lactams and acyclic amides are oxygen bases, but the gap between the oxygen and nitrogen intrinsic basicities is much smaller in the former due to the aforementioned cyclization effects. This decrease of the oxygen Modern Heterocyclic Chemistry, First Edition. Edited

show abstract

Reactivity and selectivity in the inhibition of elastase by 3-oxo-β-sultams and in their hydrolysis

Cited by 24 publications

References 24 publications

The Road to Avibactam: The First Clinically Useful Non-β-Lactam Working Somewhat Like a β-Lactam

The Road to Avibactam: The First Clinically Useful Non-β-Lactam Working Somewhat Like a β-Lactam

Structure and Reactivity of β‐Lactams

The Chemistry of 2‐Azetidinones (β‐Lactams)

Contact Info

Product

Resources

About