56741-94-7Relevant articles and documents
An efficient microwave assisted synthesis of N′-aryl/(alkyl)-substituted N-(4-hydroxy-6-phenylpyrimidin-2-yl)guanidines: Scope and limitations
Machicao, Paulo A.,Burt, Scott R.,Christensen, Ryan K.,Lohner, Nathan B.,Singleton,Peterson, Matt A.
, p. 2318 - 2321 (2017)
Treatment of N-[(4-hydroxy-6-phenyl)pyrimidin-2-yl]cyanamide with 1° alkyl or arylamines in isopropyl alcohol for only 10?min at 110–120?°C under microwave conditions gave the corresponding N′-alkyl(aryl)guanidine derivatives in excellent yields (65–84%). Isolated yields were greatest when >1.0?equiv. of amines were employed, but excellent results were also obtained when aryl and alkylamines were reacted with a more atom-economical loading (1.0?equiv.; 70% and 72% ave. yields, respectively). Arylamines with either highly electron withdrawing substituents (e.g. CO2H) or pi-deficient heterocycles (e.g. variously substituted aminopyridines) did not work well under these conditions, and reaction with ureas and/or amino acids did not give detectable products. Work-up was exceedingly simple, and involved simple collection and washing of product on a sintered glass funnel. Products were obtained in analytically pure form and required approximately 1?h to prepare, start to finish.
High-Performance Liquid Chromatographic Determination of 5-Halopyrimidinone Interferon Inducers
Wynalda, M. A.,Fitzpatrick, F. A.
, p. 1931 - 1934 (1980)
High-performance liquid chromatography with microparticulate, bonded, reversed-phase columns separates closely related 5-halopyrimidinones that are interferon inducers.A method was developed to a quantitate serum levels of 2-amino-5-bromo-6-phenyl-4(3H)-pyrimidinone, an important analogue of this new series.The method is, with minor modifications, suitable to measure other 5-halophenylpyrimidinone analoques.Results show that the quantitation of serum levels as low as 2 μg mL-1 is possible with ultraviolet detection at 235 nm.Protein precipitation and extraction prior to chromatography improve the daily sample throughput by removing interfering peaks with capacity factors greater than 45.Preliminary results indicate a species-dependent variation in the half-lives of elimination of the free compound after its administration, orally, to experimental animals.Rats clear the drug with a half-life of 4.5 h; cats clear the drug with half-lives ranging from 10 to 18 h depending on the dose administered.The differences in metabolic clearance may be relevant to observed toxicity differences between these species.
Screening of focused compound library targeting liver X receptors in pancreatic cancer identified ligands with inverse agonist and degrader activity
Karaboga, Husna,Huang, Wentao,Srivastava, Shivangi,Widmann, Scott,Addanki, Sridevi,Gamage, Kasuni Thawalama,Mazhar, Zahra,Ebalunode, Jerry O.,Briggs, James M.,Gustafsson, Jan-?ke,Filgueira, Carly S.,Gilbertson, Scott R.,Lin, Chin-Yo
, p. 2916 - 2928 (2020/11/18)
Pancreatic ductal adenocarcinoma (PDAC) is the predominant form of pancreatic cancer. PDACs harbor oncogenic mutations in the KRAS gene, and ongoing efforts to directly target its mutant protein product to inhibit tumor growth are a priority not only in pancreatic cancer but in other malignancies such as lung and colorectal cancers where KRAS is also commonly mutated. An alternative strategy to directly targeting KRAS is to identify and target druggable receptors involved in dysregulated cancer hallmarks downstream of KRAS dysregulation. Liver X receptors (LXRs) are members of the nuclear receptor family of ligand-modulated transcription factors and are involved in the regulation of genes which function in key cancer-related processes, including cholesterol transport, lipid and glucose metabolism, and inflammatory and immune responses. Modulation of LXRs via small molecule ligands has emerged as a promising approach for directly targeting tumor cells or the stromal and immune cells within the tumor microenvironment. We have previously shown that only one of the two LXR subtypes (LXRβ) is expressed in pancreatic cancer cells, and targeting LXR with available synthetic ligands blocked the proliferation of PDAC cells and tumor formation. In a screen of a focused library of drug-like small molecules predicted to dock in the ligand-binding pocket of LXRβ, we identified two novel LXR ligands with more potent antitumor activity than current LXR agonists used in our published studies. Characterization of the two lead compounds (GAC0001E5 and GAC0003A4) indicates that they function as LXR inverse agonists which inhibit their transcriptional activity. Prolonged treatments with novel ligands further revealed their function as LXR “degraders” which significantly reduced LXR protein levels in all three PDAC cell lines tested. These findings support the utility of these novel inhibitors in basic research on ligand design, allosteric mechanisms, and LXR functions and their potential application as treatments for advanced pancreatic cancer and other recalcitrant malignancies.
Synthesis of 6-arylisocytosines and their potential for hydrogen bonding interactions
Patel, Alpa,Lewis, William,Searle, Mark S.,Stevens, Malcolm F.G.,Moody, Christopher J.
supporting information, p. 7339 - 7343 (2015/08/24)
Abstract The synthesis of a number of 6-arylisocytosines, including linked bis-isocytosines, from the reaction of guanidine with β-ketoesters is described. The compounds were investigated for their ability to form hydrogen-bonded structural networks, and for their potential interactions with the telomeric quadruplex forming sequence AGGG(TTAGGG)3.
