The racemic 3-(4-oxo-3,4-dihydroquinazolin-2-yl)-N-[1-(pyridin-2-yl)ethyl]propanamide, 1, has previously been identified as a potent but unselective inhibitor of diphtheria toxin-like ADP-ribosyltransferase 3 (ARTD3). Herein we describe synthesis and evaluation of 55 compounds in this class. It was found that the stereochemistry is of great importance for both selectivity and potency and that substituents on the phenyl ring resulted in poor solubility. Certain variations at the meso position were tolerated and caused a large shift in the binding pose. Changes to the ethylene linker that connects the quinazolinone to the amide were also investigated but proved detrimental to binding. By combination of synthetic organic chemistry and structure-based design, two selective inhibitors of ARTD3 were discovered.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/jm401394u | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Sensitive Fluorescent Probe for Al, Cr and Fe: Application in Real Water Samples and Logic Gate.
J Fluoresc
January 2025
College of Chemistry and Chemical Engineering, Donghua University, Shanghai, 201620, China.
Construction of single probes for simultaneous detection of common trivalent metal ions has attracted much attention due to higher efficiency in analysis and cost. A naphthalimide-based fluorescent probe K1 was synthesized for selective detection of Al, Cr and Fe ions. Fluorescence emission intensity at 534 nm of probe K1 in DMSO/HO (9:1, v/v) was significantly enhanced upon addition of Al, Cr and Fe ions while addition of other metal ions (Li, Na, K, Ag, Cu, Fe, Zn, Co, Ni, Mn, Sr, Hg, Ca, Mg, Ce, Bi and Au) did not bring about substantial change in fluorescence emission.
View Article and Find Full Text PDFNitrogen@Carbon Quantum Dots for Fluorescence Detection of L-alanine, L-methionine and L-cysteine.
J Fluoresc
January 2025
School of Materials and Chemical Engineering, West Anhui University, Lu'an, Anhui, 237012, China.
Nitrogen@Carbon quantum dots (N@CQDs) are prepared using microwave hydrothermal method, and polyvinylpyrrolidone (PVP) and melamine are used as mixed C source and N source. Microwave reaction conditions of preparing the N@CQDs are 170 ℃ and 3 h. This N@CQDs are are used as fluorescence probe for detection of amino acids.
View Article and Find Full Text PDFEngineering Acid-Promoted Two-Photon Ratiometric Nanoprobes for Evaluating HClO in Lysosomes and Inflammatory Bowel Disease.
ACS Appl Mater Interfaces
January 2025
Anhui Provincial Key Laboratory of Biomedical Materials and Chemical Measurement, Laboratory of Functionalized Molecular Solids, Ministry of Education, College of Chemistry and Materials Science, Anhui Normal University, Wuhu 241002, P. R. China.
HClO is considered a potential contributing factor and biomarker of inflammatory bowel disease (IBD). Accurate monitoring of lysosomal HClO is important for further developing specific diagnostic and therapeutic schedules for IBD. However, only rare types of fluorescent probes have been reported for detecting HClO in IBD so far.
View Article and Find Full Text PDFPreparation of Molecularly Imprinted Electrochemical Sensors and Analysis of the Doping of Epinephrine in Equine Blood.
Sensors (Basel)
December 2024
Shandong Provincial Key Laboratory of Monocrystalline Silicon Semiconductor Materials and Technology, Shandong Provincial Engineering Research Center of Organic Functional Materials and Green Low-Carbon Technology, Shandong Universities Engineering Research Center of Integrated Circuits Functional Materials and Expanded Applications, College of Chemistry and Chemical Engineering, Dezhou University, Dezhou 253023, China.
In this paper, a novel molecularly imprinted polymer membrane modified glassy carbon electrode for electrochemical sensors (MIP-OH-MWCNTs-GCE) for epinephrine (EP) was successfully prepared by a gel-sol method using an optimized functional monomer oligosilsesquioxane-AlO sol-ITO composite sol (ITO-POSS-AlO). Hydroxylated multi-walled carbon nanotubes (OH-MWCNTs) were introduced during the modification of the electrodes, and the electrochemical behavior of EP on the molecularly imprinted electrochemical sensors was probed by the differential pulse velocity (DPV) method. The experimental conditions were optimized.
View Article and Find Full Text PDFFITA-Containing 2,4-Dinitrophenyl Alkylthioether-Based Probe for Detection and Imaging of GSH.
Sensors (Basel)
December 2024
Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China.
Glutathione (GSH) plays a crucial role in various physiological processes and its imbalances are closely related to various pathological conditions. Probes for detection and imaging of GSH are not only useful for understanding GSH chemical biology but are also important for exploring potential theranostic agents. Herein, we report a fast intramolecular thiol-activated arylselenoamides ()-based fluorescent probe using 2,4-dinitrophenyl alkylthioether as a sulfydryl-selective receptor for the first time.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!