Sulfonamide hydroxamate derivatives of anthranilic acids are known to be potent inhibitors of cell-free TACE enzyme. However, compounds of this structural class with both high potency and high selectivity for TACE over matrix metalloproteinases (MMPs) are uncommon. Replacement of the sulfonamide functionality with an isosteric sulfonate ester has resulted in a series of sulfonate ester hydroxamates, 2a-e, with excellent activity against TACE and excellent selectivity over MMP-1 and MMP-13. Although compounds 2a-e possess good permeability in a PAMPA assay, they are only weakly active as inhibitors of lipopolysaccharide (LPS)-stimulated tumor necrosis factor (TNF) production in human monocytic THP-1 cells. Protein binding affinity also does not predict the lack of cellular activity for these analogs.
We disclose a broad platform for copper-catalyzed atom transfer radical addition (ATRA) of electron-deficient olefins. Catalytic Cu(dtbbpy)(OTf) enables radical addition of electron-deficient alkyl halides to acrylates, acrylamides, and vinyl sulfones in fair to excellent yields. The resultant ATRA products can be used in a variety of telescoped reactions, including substitution with basic amine nucleophiles to afford α-amino esters.
High-voltage LiCoO is a promising cathode material for ultrahigh-energy lithium-ion batteries, particularly in the commercialization of 5G technology. However, achieving long-term operational stability remains a significant challenge. Herein, a quaterpolymer additive with multiple functional groups is introduced to enhance the electrochemical performance of LiCoO cathode at 4.
School of Pharmaceutical and Chemical Engineering & Institute for Advanced Studies, Taizhou University, 1139 Shifu Avenue, Taizhou 318000, Zhejiang, China.
An efficient synthesis of sulfonate esters through reductive addition of sodium sulfinates to pillar[4]arene[1]quinone has been established (15 examples). Compared to the arylsulfonylation of -quinone with sodium arylsulfinates under other acidic conditions, this work affords the hydroquinone-type 4--sulfonyl derivatives by using glyoxylic acid monohydrate as a promoter. The protocol features mild reaction conditions and high selectivity and is an alternative protocol for the -sulfonylation of pillar[4]arene[1]hydroquinone.
We designed novel pre-drug compounds that transform into an active form that covalently modifies particular His residue in the active site, a difficult task to achieve, and applied to carbonic anhydrase (CAIX), a transmembrane protein, highly overexpressed in hypoxic solid tumors, important for cancer cell survival and proliferation because it acidifies tumor microenvironment helping invasion and metastases processes. The designed compounds have several functionalities: (1) primary sulfonamide group recognizing carbonic anhydrases (CA), (2) high-affinity moieties specifically recognizing CAIX among all CA isozymes, and (3) forming a covalent bond with the His64 residue. Such targeted covalent compounds possess both high initial affinity and selectivity for the disease target protein followed by complete irreversible inactivation of the protein via covalent modification.
Guizhou Provincial Key Laboratory of Green Chemical and Clean Energy Technology, School of Chemistry and Chemical Engineering, Guizhou University, Guiyang 550025, China.
To tackle high viscosity in fresh concretes, especially high-performance concrete, the research of polycarboxylate superplasticizers (PCEs) is relevant. By designing the molecular structure of PCEs, problems such as pumping difficulties in high viscosity of high-performance concrete can be solved. Therefore, in this paper, a suite of novel viscosity reducing PCEs containing sulfonic acid groups and different acrylate densities were synthesized on the basis of inventive molecular structure design, and characterized to determine the predicted structure.
