132509-34-3Relevant academic research and scientific papers
Rapid and reversible hydrazone bioconjugation in cells without the use of extraneous catalysts
Nisal, Rahul,Jose, Gregor,Shanbhag, Chitra,Kalia, Jeet
supporting information, p. 4304 - 4310 (2018/06/22)
The amenability of hydrazone linkages to disassemble via either hydrolysis in mildly acidic aqueous solutions or transimination upon treatment with amine nucleophiles renders them extremely attractive for applications in chemical biology, drug delivery and materials science. Unfortunately, however, the use of hydrazones is hampered by the extremely slow intrinsic rates of their formation from their hydrazine and carbonyl precursors. Consequently, hydrazone formation is typically performed in the presence of a large excess of cytotoxic aniline-based nucleophilic catalysts, rendering hydrazones unsuitable for biological applications that entail their formation in cells. Herein, we report a hydrazine scaffold - o-amino benzyl hydrazine - that rapidly forms hydrazones via intramolecular nucleophilic catalysis, thereby obviating the use of extraneous catalysts. We demonstrate the use of this scaffold for rapid and reversible peptide and protein hydrazone bioconjugation and also for reversible fluorescent labeling of sialylated glycoproteins and choline lipids in mammalian cells.
Combinatorial aid for underprivileged scaffolds: Solution and solid-phase strategies for a rapid and efficient access to novel aza-diketopiperazines (aza-DKP)
Bonnet, Dominique,Margathe, Jean-Francois,Radford, Sally,Pflimlin, Elsa,Riche, Stephanie,Doman, Pete,Hibert, Marcel,Ganesan
, p. 323 - 334 (2012/07/13)
An efficient solution-phase synthesis of aza-diketopiperazines (aza-DKP, triazinediones) is reported. A structurally diverse collection of c-[aza-alkylGly-Pro] derivatives and yet unreported 2,4,5-trisubstituted-1,2,4- triazine-3,6-diones has been synthesized starting from Fmoc-l-Pro-OH and various Fmoc-l-amino acids. To extend the practical value of this class of dipeptidomimetics, a general solid-phase synthesis approach amenable to library production was developed on both Wang-PS and HMBA-PS resins. The final acidic treatment of the resins in TFA/water mixture at room temperature enabled the rapid and quantitative cyclization/release highly pure triazinediones. The conformational preferences and the spatial organization of the three substituents of a representative 2,4,5-trisubstituted-1,2,4-triazine-3,6-dione were investigated by X-ray diffraction and 1H NMR spectroscopy.
Pyridazinoquinolinetriones as NMDA glycine-site antagonists with oral antinociceptive activity in a model of neuropathic pain
Bare, Thomas M.,Brown, Dean G.,Horchler, Carey L.,Murphy, Megan,Urbanek, Rebecca A.,Alford, Vernon,Barlaam, Christine,Dyroff, Martin C.,Empfield, James B.,Forst, Janet M.,Herzog, Keith J.,Keith, Richard A.,Kirschner, Alan S.,Lee, Chi-Ming C.,Lewis, Joseph,McLaren, Frances M.,Neilson, Kathy L.,Steelman, Gary B.,Trivedi, Shephali,Vacek, Edward P.,Xiao, Wenhua
, p. 3113 - 3131 (2008/02/06)
A series of 7-chloro-2,3-dihydro-2-[1-(pyridinyi)alkyl]-pyridazino[4,5-b] quinoline-1,4,10(5H)-triones were synthesized and found to have potent activity at the glycine site of the NMDA receptor. In some cases, these compounds possessed poor aqueous solubility that may have contributed to poor rat oral bioavailability. Subsequently, compounds have been identified with improved aqueous solubility and oral bioavailability. Several of these compounds were examined in a rat chronic constrictive injury (CCI) model of neuropathic pain and found to have potent activity when dosed orally.
The efficient synthesis of azaamino acids
Wieczerzak,Kozlowska,Lankiewicz,Grzonka
, p. 1693 - 1697 (2007/10/03)
An efficient method of synthesis of N-t-butoxycarbonyl-azaamino acid ethyl esters has been described. This method consisted of three stages including: hydrazone formation, its reduction and acylation with ethyl chloroformate. The second step - reduction of the hydrazones to the appropriate hydrazides - was the most challenging. Some reducing agents have been tested, though NaBH3CN was found to lead to the final products with the highest yields in relatively short time and even to allow the selective reduction of C-N bond in the presence of nitro group.
