Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
The present paper describes the development of a new series of P2Y12 receptor antagonists based on our previously reported piperazinyl urea series 1 (IC50 binding affinity = 0.33 μM, aq solubility <0.1 μM, microsomal CLint (HLM) ≥300 μM/min/mg). By replacement of the urea functionality with a sulfonylurea group we observed increased affinity along with improved stability and solubility as exemplified by 47 (IC50 binding affinity = 0.042 μM, aq solubility = 90 μM, microsomal CLint (HLM) = 70 μM/min/mg). Further improvements in affinity and metabolic stability were achieved by replacing the central piperazine ring with a 3-aminoazetidine as exemplified by 3 (IC50 binding affinity = 0.0062 μM, aq solubility = 83 μM, microsomal CLint (HLM) = 28 μM/min/mg). The improved affinity observed in the in vitro binding assay also translated to the potency observed in the WPA aggregation assay (47: 19 nM and 3: 9.5 nM) and the observed in vitro ADME properties translates to the in vivo PK properties observed in rat. In addition, we found that the chemical stability of the sulfonylureas during prolonged storage in solution was related to the sulfonyl urea linker and depended on the type of solvent and the substitution pattern of the sulfonyl urea functionality.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ejmech.2013.04.007 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Synthesis and Optical Properties of Trivalent Metal Methanesulfonates Containing Y(III), Bi(III), In(III), and Sb(III).
Inorg Chem
September 2025
University of Houston, Department of Chemistry, Houston, Texas 77204-5003, United States.
Methanesulfonate salts have garnered interest as candidates for optical crystals; however, there are relatively little empirical data to thoroughly understand their structure-property relationships. Furthermore, there is only one trivalent main group methanesulfonate reported in the solid state, Al(HO)(SOCH). We report the synthesis and characterization of four new trivalent methanesulfonates, such as () Y(SOCH), () Bi(SOCH), () In(SOCH)(HO), and () SbO(OH)(SOCH).
View Article and Find Full Text PDFHydrothermal lignin microspheres: Synthesis, structural evolution, and antibacterial performance.
Int J Biol Macromol
September 2025
College of Chemical Engineering and Materials Science, Tianjin University of Science and Technology, Tianjin, China. Electronic address:
This study reported a modified hydrothermal solvent method for preparing lignin microspheres (LNSs) with controllable size and morphology by precisely regulating the reaction temperature (160-220 °C). Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM) were employed to evaluate the structure, morphological, and dimensional attributes of lignin microspheres, and the synthesis mechanism was discussed. The antibacterial efficacy of the hydrothermally treated lignin microspheres (HTLNSs) was evaluated through phosphate-buffered saline (PBS) culture assays, as well as by assessing nucleic acid and protein leakage, and their inhibitory effect on cell membrane permeability.
View Article and Find Full Text PDFProperties and Characterization of Cryogels: Structural, Mechanical, and Functional Insights.
ACS Omega
August 2025
Symbiosis Centre for Stem Cell Research, Symbiosis International (Deemed University), Pune 412115, India.
Cryogels are a distinct class of macroporous polymeric materials formed through cryopolymerization, where precursor monomers and polymers undergo polymerization and cross-linking under freezing conditions. Unlike conventional hydrogels, which exhibit nanoscale porosity and are synthesized at ambient temperatures, cryogels feature interconnected micrometer-sized pores that confer unique mechanical, structural, and functional properties. Their high porosity, rapid hydration, and efficient mass transport make them highly desirable for tissue engineering, biosensing, drug delivery, and environmental remediation applications.
View Article and Find Full Text PDFHigh-Performance Polyimide Design: Machine Learning-Accelerated Multiobjective Optimization.
ACS Appl Mater Interfaces
September 2025
Research Center of Nano Science and Technology, College of Sciences, Shanghai University, Shanghai 200444, P. R. China.
Polyimides (PIs) with superior transparency, mechanical robustness, and thermal stability are essential for advanced applications such as flexible electronics, foldable displays, and aerospace components, but simultaneous optimization of these properties remains challenging. Here, we present a data-driven multiobjective optimization framework for systematic polyimide design, supported by high-quality data sets extracted with the assistance of large language models. Leveraging robust machine learning models validated by the experimental synthesis and evaluation of five PI films, our method precisely predicts material performance and effectively deciphers complex structure-property relationships influenced by charge transfer complexes.
View Article and Find Full Text PDFSolvent-Driven Precise Control of Stacking Configurations in Covalent Organic Frameworks for High-Efficiency Photocatalysis.
Angew Chem Int Ed Engl
August 2025
School of Energy and Environment, Southeast University, Nanjing, 211189, China.
Two-dimensional covalent organic frameworks (2D COFs) have emerged as promising photocatalysts due to their high surface areas and precisely tunable physicochemical properties. However, it remains a significant challenge to precisely control over interlayer stacking configurations in 2D COFs, which critically influence charge carrier transport and consequently determine catalytic efficiency. In this study, we demonstrate a solvent-driven strategy to precisely regulate the interlayer stacking configurations of metal-incorporated 2D COFs, successfully achieving both AA eclipsed (COF-TD-AA) and ABC staggered (COF-TD-ABC) configurations.
View Article and Find Full Text PDF