1129-26-6Relevant articles and documents
Rational Design, synthesis and biological evaluation of novel triazole derivatives as potent and selective PRMT5 inhibitors with antitumor activity
Zhu, Kongkai,Shao, Jingwei,Tao, Hongrui,Yan, Xue,Luo, Cheng,Zhang, Hua,Duan, Wenhu
, p. 775 - 785 (2019)
Protein arginine methyltransferase 5 (PRMT5) is responsible for the mono-methylation and symmetric dimethylation of arginine, and its expression level and methyl transferring activity have been demonstrated to have a close relationship with tumorigenesis, development and poor clinical outcomes of human cancers. Two PRMT5 small molecule inhibitors (GSK3326595 and JNJ-64619178) have been put forward into clinical trials. Here, we describe the design, synthesis and biological evaluation of a series of novel, potent and selective PRMT5 inhibitors with antiproliferative activity against Z-138 mantle cell lymphoma cell line. Among them, compound C_4 exhibited the highest potency with enzymatic and cellular level IC50 values of 0.72 and 2.6 μM, respectively, and displayed more than 270-fold selectivity toward PRMT5 over several other isoenzymes (PRMT1, PRMT4 and PRMT6). Besides, C_4 demonstrated obvious cell apoptotic effect while reduced the cellular symmetric arginine dimethylation levels of SmD3 protein. The potency, small size, and synthetic accessibility of this compound class provide promising hit scaffold for medicinal chemists to further explore this series of PRMT5 inhibitors.
A general iodine-mediated synthesis of primary sulfonamides from thiols and aqueous ammonia
Feng, Jian-Bo,Wu, Xiao-Feng
, p. 6951 - 6954 (2016)
A general and efficient methodology for preparing primary sulfonamides has been developed. In the presence of iodine as the catalyst and TBHP (70% in water) as the oxidant, a wide range of primary sulfonamides were prepared from the corresponding thiols and aqueous ammonia in moderate to good yields.
SuFEx Activation with Ca(NTf2)2: A Unified Strategy to Access Sulfamides, Sulfamates, and Sulfonamides from S(VI) Fluorides
Am Ende, Christopher W.,Ball, Nicholas D.,Bellenger, Justin,Butler, Todd W.,Carneiro, Sabrina N.,Dutra, Jason K.,Gu, Junha,Khasnavis, Samuel R.,Kwan, Sabrina C.,Mahapatra, Subham,Vetelino, Beth C.,Woroch, Cristian P.
, (2020)
A method to activate sulfamoyl fluorides, fluorosulfates, and sulfonyl fluorides with calcium triflimide and DABCO for SuFEx with amines is described. The reaction was applied to a diverse set of sulfamides, sulfamates, and sulfonamides at room temperature under mild conditions. Additionally, we highlight this transformation to parallel medicinal chemistry to generate a broad array of nitrogen-based S(VI) compounds.
Tetrahydropyridines via FeCl3-Catalyzed Carbonyl-Olefin Metathesis
Gaviria, Mario A.,Groso, Emilia J.,Richardson, Alistair D.,Rykaczewski, Katie A.,Schindler, Corinna S.,Vonesh, Hannah L.,Zehnder, Troy E.
, (2020)
Herein we describe the application of Lewis-acid-catalyzed carbonyl-olefin metathesis toward the synthesis of substituted tetrahydropyridines from commercially available amino acids as chiral pool reagents. This strategy relies on FeCl3 as an inexpensive and environmentally benign catalyst and enables access to a variety of substituted tetrahydropyridines under mild reaction conditions. The reaction proceeds with complete stereoretention and is viable for a variety of natural and unnatural amino acids to provide the corresponding tetrahydropyridines in up to 99% yield.
Metal-free construction of primary sulfonamides through three diverse salts
Wang, Ming,Fan, Qiaoling,Jiang, Xuefeng
, p. 5469 - 5473 (2018)
In this report, the first metal-free construction of primary sulfonamides through a direct three-component reaction of sodium metabisulfite, sodium azide and aryldiazonium has been established. Readily available inorganic Na2S2O5 and NaN3 were applied as the sulfur dioxide surrogate and nitrogen source respectively. The widely used sulfonamide drugs Celecoxib and Sulpiride, which possess multiple heteroatoms and active hydrogen containing functional groups, are efficiently installed with -SO2NH2 groups at a late stage. Control experiments and kinetic studies demonstrated that aryl radicals, sulfonyl radicals and conjugated phosphine imine radicals are involved in this transformation.
Deconstructing Noncovalent Kelch-like ECH-Associated Protein 1 (Keap1) Inhibitors into Fragments to Reconstruct New Potent Compounds
Pallesen, Jakob S.,Narayanan, Dilip,Tran, Kim T.,Solbak, Sara M. ?.,Marseglia, Giuseppe,S?rensen, Louis M. E.,H?j, Lars J.,Munafò, Federico,Carmona, Rosa M. C.,Garcia, Anthony D.,Desu, Haritha L.,Brambilla, Roberta,Johansen, Tommy N.,Popowicz, Grzegorz M.,Sattler, Michael,Gajhede, Michael,Bach, Anders
supporting information, p. 4623 - 4661 (2021/05/07)
Targeting the protein-protein interaction (PPI) between nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) is a potential therapeutic strategy to control diseases involving oxidative stress. Here, six classes of known small-molecule Keap1-Nrf2 PPI inhibitors were dissected into 77 fragments in a fragment-based deconstruction reconstruction (FBDR) study and tested in four orthogonal assays. This gave 17 fragment hits of which six were shown by X-ray crystallography to bind in the Keap1 Kelch binding pocket. Two hits were merged into compound 8 with a 220-380-fold stronger affinity (Ki = 16 μM) relative to the parent fragments. Systematic optimization resulted in several novel analogues with Ki values of 0.04-0.5 μM, binding modes determined by X-ray crystallography, and enhanced microsomal stability. This demonstrates how FBDR can be used to find new fragment hits, elucidate important ligand-protein interactions, and identify new potent inhibitors of the Keap1-Nrf2 PPI.
Unlocking Amides through Selective C–N Bond Cleavage: Allyl Bromide-Mediated Divergent Synthesis of Nitrogen-Containing Functional Groups
Govindan, Karthick,Chen, Nian-Qi,Chuang, Yu-Wei,Lin, Wei-Yu
, p. 9419 - 9424 (2021/11/30)
We report a new set of reactions based on the unlocking of amides through simple treatment with allyl bromide, creating a common platform for accessing a diverse range of nitrogen-containing functional groups such as primary amides, sulfonamides, primary amines, N-acyl compounds (esters, thioesters, amides), and N-sulfonyl esters. The method has potential industrial applicability, as demonstrated through gram-scale syntheses in batch and in a continuous flow system.
