216067-79-7Relevant academic research and scientific papers
O-Protected N-(2-Nitrophenylsulfonyl)hydroxylamines: Novel Reagents for the Synthesis of Hydroxamates
Reddy, Poreddy Amruta,Schall, Otto F.,Wheatley, James R.,Rosik, Leonard O.,McClurg, Joseph P.,Marshall, Garland R.,Slomczynska, Urszula
, p. 1086 - 1092 (2001)
Preparative methods for novel O-protected N-(2-nitrophenylsulfonyl)hydroxylamines (8a-e) are described. Their versatility as intermediates en route to polyhydroxamates is examplified by the synthesis of a non-amide DFO analog 22.
Design, synthesis and molecular modeling study of iminodiacetyl monohydroxamic acid derivatives as MMP inhibitors
Amelia Santos,Marques, Sergio M.,Tuccinardi, Tiziano,Carelli, Paolo,Panelli, Laura,Rossello, Armando
, p. 7539 - 7550 (2008/02/09)
As the matrix metalloproteinases (MMPs) can be massively up-regulated in degenerative tissues and degrade the extracellular matrix, these key enzymes are promising targets for the therapy of cancer and other degenerative diseases. Here, we are presenting a series of new non-peptidic hydroxamate-based matrix metalloproteinase inhibitors, MMPIs, incorporating the iminodiacetic (IDA) hydroxamic acid scaffold, as mimics of truncated peptidic MMPIs. A series of alkylaryl and sulfonylaryl groups, on the IDA basic scaffold, was investigated with the aim of improving potency and selectivity against MMPs involved in degenerative diseases. The sulfonamide based IDA derivatives studied (compounds B1-B3) showed to be potent (nM range) against deep S1′ pocket MMPs enzymes (i.e., MMP-2).
High-throughput catch-and-release synthesis of oxazoline hydroxamates. Structure-activity relationships in novel inhibitors of Escherichia coli LpxC: In vitro enzyme inhibition and antibacterial properties
Pirrung, Michael C.,Tumey, L. Nathan,McClerren, Amanda L.,Raetz, Christian R. H.
, p. 1575 - 1586 (2007/10/03)
LpxC is a zinc amidase that catalyses the second step of lipid A biosynthesis in Gram-negative bacteria. Oxazolines incorporating a hydroxamic acid, which is believed to coordinate to the single essential zinc ion, at the 4-position are known inhibitors of this enzyme. Some of these enzyme inhibitors exhibit antibacterial activity through their inhibition of LpxC. We recently developed a method for the synthesis of oxazolines using resin capture and ring-forming release that eliminates traditional purification steps and can be used in high-throughput synthesis. Using our method, oxazoline hydroxamates with diverse 2-substituents were prepared in library form as candidate inhibitors for LpxC. Two conventional methods for oxazoline synthesis were also applied to generate more than 70 compounds. The groups at the 2-position included a wide variety of substituted aromatic rings and a limited selection of alkyl groups. These compounds were screened against wild-type and LpxC inhibitor-sensitive strains of Escherichia coli, as well as wild-type Pseudomonas aeruginosa. Inhibition of the E. coli LpxC enzyme was also investigated. A broad correlation between enzyme inhibitory and antibacterial activity was observed, and novel compounds were discovered that exhibit antibacterial activity but fall outside earlier-known structural classes.
New hydroxylamines for the synthesis of hydroxamic acids
Barlaam, Bernard,Hamon, Annie,Maudet, Mickael
, p. 7865 - 7868 (2007/10/03)
O-2,4-Dimethoxybenzyl hydroxylamine and O-2,4-dimethoxybenzyl-N-2,4,6- trimethoxybenzyl hydroxylamine have been prepared and used for the preparation of hydroxamic acid based inhibitors of biological interest.
