Carbamate–drug conjugates in drug delivery: structural and mechanistic considerations

Chaudhary, Jasmine; Jain, Akash; Malik, Garima

doi:10.1016/b978-0-323-91663-9.00001-1

Cited by 2 publications

(2 citation statements)

References 49 publications

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“…With previous positive experience using the versatile carbamate‐based amine release, it was envisaged that a stable linkage and controllable amide release could be enabled by utilising an aminomethyl carbamate linkage between the desired amide and the trigger component (Figure 1c). Carbamates are widely used in self‐immolative linker systems as they have drug‐like properties, stability when incorporated into a linker, and crucially can be readily eliminated following a trigger event [53] . In this case, the carbamate is eliminated by an appendaged trigger to reveal an unstable terminal carbamic acid that spontaneously releases CO 2 , affording an N ‐aminomethyl amide.…”

Section: Resultsmentioning

confidence: 99%

Unlocking Amides: A General Method for the Self‐Immolative Release of Amide‐Containing Molecules

Wharton,

Crawshay‐Williams,

Schober

et al. 2024

Angewandte Chemie

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The controlled liberation of molecules from a constructed framework is a subject of profound interest across various chemical fields. It allows for the masking of a molecule's properties and precise deployment upon a single controllable release event. While numerous methodologies have been developed for amines, alcohols, and thiols, approaches for utilising amides as payload‐release handles are still in their early stages of development, despite the prevalence of amides in therapeutic compounds and materials. Herein, is presented a comprehensive strategy for the controlled and selective release of a diverse range of amides with stable linkers. The versatility of this approach is demonstrated by its successful application in the targeted release of various amide‐containing drugs in their natural form via the use of commonly used trigger motifs, such as dipeptides or glycosides. As a proof‐of‐concept, the FDA‐approved antibiotic linezolid has been successfully converted into a prodrug form and released selectively only in the presence of the trigger event. Significantly, in its prodrug state, no activity against Mycobacterium tuberculosis was exhibited. Linezolid's full potential was achieved only upon controlled release, where an equipotent efficacy to the free linezolid control was demonstrated, thus emphasising the immense potential of this method.

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Section: Resultsmentioning

confidence: 99%

Unlocking Amides: A General Method for the Self‐Immolative Release of Amide‐Containing Molecules

Wharton,

Crawshay‐Williams,

Schober

et al. 2024

Angewandte Chemie

View full text Add to dashboard Cite

show abstract

“…Carbamates are widely used in self-immolative linker systems as they have drug-like properties, stability when incorporated into a linker, and crucially can be readily eliminated following a trigger event. [53] In this case, the carbamate is eliminated by an appendaged trigger to reveal an unstable terminal carbamic acid that spontaneously releases CO 2 , affording an N-aminomethyl amide. This can then degrade via an aminal-type mechanism to release the native parent amide (Figure 1c), [38] similar to methods previously used to release alcohols.…”

Section: Resultsmentioning

confidence: 99%

Unlocking Amides: A General Method for the Self‐Immolative Release of Amide‐Containing Molecules

Wharton,

Crawshay‐Williams,

Schober

et al. 2024

Angew Chem Int Ed

View full text Add to dashboard Cite

show abstract

Carbamate–drug conjugates in drug delivery: structural and mechanistic considerations

Cited by 2 publications

References 49 publications

Unlocking Amides: A General Method for the Self‐Immolative Release of Amide‐Containing Molecules

Unlocking Amides: A General Method for the Self‐Immolative Release of Amide‐Containing Molecules

Unlocking Amides: A General Method for the Self‐Immolative Release of Amide‐Containing Molecules

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