14849-47-9Relevant academic research and scientific papers
From solution to in-cell study of the chemical reactivity of acid sensitive functional groups: A rational approach towards improved cleavable linkers for biospecific endosomal release
Jacques, Sylvain A.,Leriche, Geoffray,Mosser, Michel,Nothisen, Marc,Muller, Christian D.,Remy, Jean-Serge,Wagner, Alain
supporting information, p. 4794 - 4803 (2016/06/13)
pH-Sensitive linkers designed to undergo selective hydrolysis at acidic pH compared to physiological pH can be used for the selective release of therapeutics at their site of action. In this paper, the hydrolytic cleavage of a wide variety of molecular structures that have been reported for their use in pH-sensitive delivery systems was examined. A wide variety of hydrolytic stability profiles were found among the panel of tested chemical functionalities. Even within a structural family, a slight modification of the substitution pattern has an unsuspected outcome on the hydrolysis stability. This work led us to establish a first classification of these groups based on their reactivities at pH 5.5 and their relative hydrolysis at pH 5.5 vs. pH 7.4. From this classification, four representative chemical functions were selected and studied in-vitro. The results revealed that only the most reactive functions underwent significant lysosomal cleavage, according to flow cytometry measurements. These last results question the acid-based mechanism of action of known drug release systems and advocate for the importance of an in-depth structure-reactivity study, using a tailored methodology, for the rational design and development of bio-responsive linkers.
Synthesis and solid state structure of a hydrazone-disulfide macrocycle and its dynamic covalent ring-opening under acidic and basic conditions
Von Delius, Max,Geertsema, Edzard M.,Leigh, David A.,Slawin, Alexandra M. Z.
experimental part, p. 4617 - 4624 (2010/11/19)
The synthesis and characterisation, including solid state structure, of a macrocycle containing both a hydrazone and a disulfide linkage is described. Selective ring-opening of the macrocycle under thermodynamic control could be achieved at either the dis
Toward a versatile allylation reagent: Practical, enantioselective allylation of acylhydrazones using strained silacycles
Berger, Richard,Rabbat, Philippe M. A.,Leighton, James L.
, p. 9596 - 9597 (2007/10/03)
A highly practical method for the enantioselective allylation of acylhydrazones has been developed. The previously reported strained silacycle reagent 1 reacts with a wide variety of acylhydrazones to give the hydrazide products with good enantioselectivi
