10.1016/j.jfluchem.2007.07.003
The research focuses on improving the bioavailability of peptide drugs, especially addressing the poor biological membrane permeability and rapid metabolism of drugs such as enkephalins. To overcome these challenges, the study investigated the synthesis and lipophilicity measurements of Na/N-terminal-1,1-dihydroperfluoroalkylated a-amino acids and small peptides. The experiments involved the synthesis of specific (1,1-dihydroperfluoroalkyl)phenyliodonium N,N-bis(trifluoromethylsulfonyl)imide, which was then used to transfer the 1,1-dihydroperfluoroalkyl group to the a-amino group of (L) tyrosine. The resulting Na-2,2,2-trifluoroethylated (L) tyrosine was used for the solid phase peptide synthesis of leucine enkephalin analogs. The lipophilicity of these perfluoroalkylated (L) tyrosine and N-terminal-2,2,2-trifluoroethylated leucine enkephalin analogs was measured and compared with the parent compound. Reactants included (L) tyrosine, iodine salts, and various reagents for the synthetic process, while analyses included NMR spectroscopy, UV measurements, and partition coefficient calculations to assess lipophilicity.
10.1039/c0sm01087a
The research focuses on the development of antibacterial soft nanocomposites through the in situ synthesis of silver nanoparticles (AgNPs) within the self-assemblies of amino acid-based amphiphilic hydrogelators. The study aims to create materials effective against both Gram-positive and Gram-negative bacteria, without the need for external reducing or stabilizing agents. The experiments involved the synthesis of AgNPs using Tollens' reagent and amphiphilic hydrogelators derived from amino acids like tryptophan and tyrosine. The nanocomposites were characterized using UV-vis spectra, TEM, XRD, and TGA. The antibacterial activity was evaluated against various bacterial strains, and biocompatibility was assessed with mammalian cells, NIH3T3. The research also explored the influence of the head group charge and structure of the amphiphiles on the synthesis, stabilization of AgNPs, and the antibacterial activity of the nanocomposites. Notably, the soft nanocomposites demonstrated excellent antibacterial activity and considerable biocompatibility, showing potential for use in biomedical applications, including tissue engineering scaffolds.
10.1016/j.bmcl.2008.06.106
Imidazole vinyl pyrimidines were identified as novel kinase inhibitors that target Tie-2, a receptor tyrosine kinase involved in angiogenesis and human tumor growth. The study describes the synthesis, structure-activity relationship (SAR), and biological evaluation of these compounds. Synthesis was achieved by condensation of imidazole aldehydes with methyl pyrimidines, resulting in lead compounds with low molecular weight, good physical properties, and oral bioavailability. Experiments included high-throughput screening (HTS) to identify the initial hit, compound 1, which exhibited ATP-competitive inhibition of Tie-2 with an IC50 of 6 μM. Cellular potency was assessed using a phosphorylated Tie-2 cell-based ELISA assay, and selectivity was evaluated in a panel of kinase assays. The study also involved modifications of the phenyl ring, the amino substituent of the pyrimidine ring, and the imidazothiazole ring to explore the importance of various structural features. Analytical methods included 1H NMR isomer assignments, IC50 determinations (for both enzyme and cell assays), and oral bioavailability assessments in mouse dosing experiments. This study aimed to identify potent and selective Tie-2 inhibitors with good oral bioavailability, thus identifying compound 26 as a promising drug candidate.
10.1016/j.bmc.2015.09.050
The study presents the design, synthesis, and characterization of ultrasmall dual-modality silica nanoparticle drug conjugates (NDCs) for cancer therapy. These NDCs utilize protease-sensitive linkers to attach drug compounds and imaging labels to ultrasmall silica nanoparticles (C' dots), enabling controlled drug release and dual-modality imaging (PET and optical). The primary chemicals used include gefitinib analogs, which are epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), and various linkers incorporating dipeptide enzyme substrates. These linkers are designed to be cleaved by proteases, facilitating drug release at the tumor site. The study also involves the synthesis of maleimide-functionalized C' dots and the conjugation of linker-drug constructs to these particles. The purpose of these chemicals is to create a nanotherapeutic platform that can deliver drugs directly to cancer cells, enhance imaging capabilities for better disease monitoring, and potentially improve treatment efficacy while reducing side effects.
10.1021/jo702573z
The study focuses on the synthesis and structural characterization of novel spirobarbiturates as effective β-turn mimetics, which are important for molecular recognition and signal transduction. The researchers synthesized spirobarbiturates of type III using N-carbamoyl-substituted amino acids and pyrrolidine-1,2,2-tricarboxylic acid derivatives through cyclocondensation reactions. Key chemicals used in the study included N-Boc-protected diethylaminomalonate, 1,3-dibromopropane, and various urea derivatives (e.g., N-carbamoyl glycine, phenylalanine, and tyrosine), which served as building blocks in the synthesis process. The introduction of these compounds aimed to create molecular scaffolds that could be utilized as biomolecular probes to explore binding interactions with target proteins, ultimately contributing to the development of peptide mimetics with potential therapeutic applications.
10.1016/j.tetasy.2008.09.009
The research aimed to evaluate the influence of a sterically less demanding substituent at C(2) on the regioselectivity of Fischer indolization and to gain insight into the stereolability of pyrrolocarbazoles obtained from β-amino ketones. The study concluded that the α-carbon of the amino ester in polycyclic proline analogues showed stereolability in an acetic medium at 80–90°C, and there is a possibility of epimerization or racemization in pyrrolo[3,2-c] and pyrrolo[2,3-b]carbazoles when working with acetic or p-toluenesulfonic acid, as these compounds are prone to retro-Pictet Spengler and fragmentation processes, leading to the loss of their stereochemical integrity. Key chemicals used in the process included enantiopure 2-methoxycarbonyl-cis-octahydroindol-6-ones, acetic acid (AcOH), p-toluenesulfonic acid (TsOH), phenylhydrazine, and L-tyrosine as the chiral starting material.
10.1021/acs.oprd.9b00227
This study presents a new method for synthesizing Imatinib, a tyrosine kinase inhibitor used in treating chronic myeloid leukemia, through a C–N coupling reaction. The key chemicals involved include 4-(4-methylpiperazine-1-methyl)benzamide and N-(5-bromo-2-tolyl)-4-(3-pyridyl)pyrimidin-2-amine, which are coupled to form Imatinib. Nano-ZnO and KOH play crucial roles as catalysts in the hydrolysis of 4-(4-methylpiperazine-1-methyl)benzonitrile to produce the corresponding amide. The study highlights the efficiency and selectivity of nano-ZnO in this process. The new synthetic route avoids the production of genotoxic impurities, as classified by the FDA, and offers an environmentally friendly approach with a short reaction time and high purity of the final product.
10.1016/S0040-4020(01)87469-X
The study investigates the biosynthesis of alkaloids in Corydalis meifolia Wall., a plant used in traditional medicine. The researchers used tracer experiments to demonstrate that the alkaloids corlumine, cavidine, and yenshusomine are stereospecifically biosynthesized from (R)-(?)-reticuline. They fed various labeled precursors, including tyrosine, norreticuline, and reticuline, to young branches of the plant and observed the incorporation of these precursors into the target alkaloids. The results showed that certain precursors, like norreticuline and reticuline, were efficiently metabolized into the alkaloids, while others were not. The study also established the regiospecificity of the biosynthetic pathway by tracking the labeled atoms through various chemical transformations, confirming that reticuline is a true precursor of these alkaloids. The findings provide valuable insights into the biogenetic pathway of these medically relevant compounds.
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