10.1016/j.ejmech.2010.01.032
The study focuses on the synthesis and evaluation of a series of new acrylamide derivatives containing 1,2,3-thiadiazole for their potential antiviral activity against hepatitis B virus (HBV) replication. These compounds were designed based on the structure of known anti-HBV agents and synthesized through various chemical reactions. The in vitro anti-HBV activities were assessed by measuring the inhibition of HBV DNA replication, secretion of HBeAg, and HBsAg in 2.2.15 cells. The results showed that several compounds, particularly 9c, demonstrated higher inhibitory activity against HBV DNA replication compared to the positive control lamivudine. Additionally, compound 9d exhibited significant activity against the secretion of HBeAg. The study concludes that these acrylamide derivatives containing 1,2,3-thiadiazole could serve as promising candidates for the development of new anti-HBV drugs.
10.1021/jm049022c
The research focuses on the discovery, synthesis, and characterization of novel furanopyrimidine and pyrrolopyrimidine inhibitors targeting the Chk1 kinase, a significant enzyme in cancer cell cycle regulation. The study combines computational modeling with experimental validation to optimize inhibitor design. Reactants used in the synthesis include commercially available starting compounds and aminofuran derivatives, which undergo a series of chemical transformations involving condensation, cyclization, chlorination, and displacement reactions to produce the desired inhibitors. 5,6-Diphenylfurano[2,3-d]pyrimidin-4-ylamine, ethanolamine, N-methylethanolamine, glycine, 2-phenylethanol, (2-aminoethyl)-carbamic acid tert-butyl ester and O-methylethanolamine were used as starting materials. The synthesized compounds are then crystallographically analyzed to determine their binding mode to the Chk1 kinase. Experiments include X-ray crystallography to resolve the protein-inhibitor complex structures, kinetic assays to measure inhibitor potency, and molecular modeling to predict binding modes and optimize compound affinity. The research also explores the impact of hydrogen bonding on protein-ligand interactions and binding affinity through structural and thermodynamic analysis.
10.1007/s13361-018-1998-7
The research focuses on the identification of epitope ligand binding sites of blood group oligosaccharides in lectins using a combination of pressure-assisted proteolytic excision and extraction, followed by affinity mass spectrometry (MS) analysis. The study employs human galectin-3 and glycine max lectin as model blood group-specific lectins. The experimental workflow involves immobilizing carbohydrates on affinity columns, allowing lectins to bind, and then subjecting the complex to proteolytic digestion. The resulting peptide fragments are analyzed using MALDI and ESI mass spectrometry to identify the specific epitope peptides involved in carbohydrate recognition. The study also utilizes pressure-enhanced digestion with an automated Barocycler procedure to improve the efficiency of proteolytic extraction/excision-MS. Additionally, synthetic peptide ligands with immobilized carbohydrates are used for affinity studies to ascertain the specificities of the epitope ligands for individual carbohydrates. The binding affinities of these synthetic ligand peptides are determined by surface acoustic wave (SAW) biosensor analysis, providing insights into their interactions with lactose and other carbohydrates.
10.1016/S0960-894X(99)00194-8
The research aimed to design, synthesize, and investigate the structure-activity relationships of novel ligands that act at the strychnine-insensitive glycine site of the NMDA receptor. This site is of interest due to its potential therapeutic relevance in various disorders, including cognitive deficits, epilepsy, schizophrenia, pain, depression, and stroke. The study focused on 3-hydroxy-imidazolidin-4-one derivatives, using D-cycloserine (DCS) and L-687,414 as templates due to their rigid framework and spatial orientation of pharmacophores. The researchers synthesized a series of compounds and evaluated their affinities and efficacies at the target site. The most active compound, 3a, exhibited affinity and efficacy similar to DCS, a known partial agonist. However, modifications to the structure of 3a, such as the addition of methyl or hydroxymethyl groups, expansion of the ring size, or replacement of the basic nitrogen with a sulfur atom, generally led to a loss of activity.
10.1007/s00044-010-9364-8
This research presents the synthesis and evaluation of novel prodrugs of naproxen, a nonsteroidal anti-inflammatory drug (NSAID), aimed at enhancing its pharmaceutical and pharmacokinetic properties while reducing gastrointestinal (GI) toxicity. The study involved the reaction of naproxen with thionyl chloride to form an acid chloride, which was then reacted with glucose to produce glucosyl naproxen. This was followed by acetylation and reaction with various amino acids to yield the prodrugs. The synthesized prodrugs were evaluated for analgesic and anti-inflammatory activities and assessed for GI toxicity. The results indicated that the prodrugs maintained the therapeutic activities of naproxen while significantly reducing GI irritation. Key chemicals used in the synthesis process included naproxen, thionyl chloride, glucose, pyridine, acetic anhydride, and different amino acids such as glycine, valine, alanine, cysteine, and others. The synthesized compounds were characterized using IR, NMR, and MS spectral methods. The study concluded that these novel prodrugs could be potentially useful naproxen derivatives for oral administration due to their stability in aqueous solutions, retention of analgesic and anti-inflammatory activity, and notably reduced GI irritation.
10.1021/acschemneuro.7b00117
The study aims to exploit structural differences in the agonist binding domains (ABDs) of NMDA receptors to develop ligands that can differentiate between glycine binding sites in a GluN2 subunit-dependent manner. The researchers synthesized a series of amino acids with bulky substituents and characterized their agonist activities using two-electrode voltage-clamp electrophysiology on recombinant NMDA receptor subtypes (GluN1/2A-D). The results revealed significant variation in subunit-selectivity, potency, and agonist efficacy among the tested compounds. Notably, compounds 15a and 16a exhibited superagonist activity at the GluN1/2C receptor subtype, with agonist efficacies of 398% and 308% compared to glycine, respectively. Molecular modeling supported the hypothesis that larger ligand substituents can interact with residues in the ABD dimer interface, contributing to GluN2-specific activity. This study demonstrates the potential for developing subtype-selective NMDA receptor ligands and highlights opportunities for further exploration of glycine-site agonists in studying GluN2-specific effects in NMDA receptor-mediated neurotransmission.
10.1016/j.tetlet.2008.07.103
Lal Dhar S. Yadav and Ankita Rai present a novel and operationally simple method for synthesizing a-amino acids and a-mercapto acids by directly introducing glycine or mercaptoacetic acid units into electron-poor alkenes. The study utilizes a Lewis acid-catalyzed Michael addition of activated glycine or mercaptoacetic acid derivatives to various electron-poor alkenes in a water/1,4-dioxane solvent system at ambient temperature. The optimized reaction conditions involve using CeCl3·7H2O/NaI as the catalyst, achieving high yields (82-93%) and diastereoselectivity favoring the syn isomer (93-96%). The method is versatile, allowing for the installation of multiple functional groups such as amino, mercapto, carboxylic acid, nitro, ester, cyano, and aryl groups on the activated olefinic double bond of methyl acrylate, acrylonitrile, and nitrostyrenes. This one-pot procedure offers a practical and efficient route for the synthesis of these chemically and pharmacologically relevant compounds, which have significant applications in organic synthesis and medicinal chemistry.
