402-46-0Relevant articles and documents
P2X7R ANTAGONISTS
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Page/Page column 27-28, (2021/01/23)
A compound has Formula I: (I). R1 is hydrogen, hydroxy, halogen, nitro, amino, alkyl, alkoxy, alkylamino, cycloalkyl, cycloalkyamino, heterocyclyl, aryl, heteroaryl, -NR7R8, -CO-R10, or -NH-CO-R10; L is a bond, a heterocyclic bivalent group, a heteroaromatic bivalent group, or an aromatic bivalent group; M is a bond, alkyl, aryl, heterocyclic bivalent group, heteroaromatic bivalent group, or aromatic bivalent group; X is a bond, -O-, -S-, -SO2-, -CO-, -NR9-, -(CH2)m-, or heterocyclic bivalent group, m is 1, 2, 3, 4, 5, or 6; Y is a bond, -NH-, heterocyclic bivalent group, heteroaromatic bivalent group, bivalent benzyl group, or aromatic bivalent group; and Z is hydrogen, halogen, alkyl, aryl, heterocyclyl, heteroaryl, -NR7R8, -CO-R10, or -NH-CO-R10; R7, R8, and R9 are independently hydrogen, hydroxy, halogen, nitro, amino, alkyl, alkoxy, alkylamino, cycloalkyl, cycloalkyamino, heterocyclyl, or heteroaryl; and R10 is -O-tert-butyl, -CH2CH2-phenyl, hydrogen, hydroxy, halogen, nitro, amino, alkyl, alkoxy, alkylamino, cycloalkyl, cycloalkyamino, heterocyclyl, or heteroaryl.
Fluorescence Assisted Capillary Electrophoresis of Glycans Enabled by the Negatively Charged Auxochromes in 1-Aminopyrenes
Savicheva, Elizaveta A.,Seikowski, Jan,Kast, Jeannette I.,Grünig, Christoph R.,Belov, Vladimir N.,Hell, Stefan W.
supporting information, p. 3720 - 3726 (2020/12/22)
A compact and negatively charged acceptor group, N-(cyanamino)sulfonyl, is introduced for dye design and its influence on the absorption and emission spectra of the “push–pull” chromophores is demonstrated with 1,3,6-tris[(cyanamino)sulfonyl]-8-aminopyrene. The new sulfonamides, including O-phosphorylated (3-hydroxyazetidine)-N-sulfonyl, are negatively charged electron acceptors and auxochromes. 1-Aminopyrenes decorated with the new sulfonamides have three or six negative charges (pH ≥8), low m/z ratios, high mobilities in an electric field, and yellow to orange emission. We labeled maltodextrin oligomers by reductive amination, separated the products by electrophoresis, and demonstrated their high brightness in a commercial DNA analyzer and the distribution of the emission signal among the detection channels.
Radical Decarboxylative Carbometalation of Benzoic Acids: A Solution to Aromatic Decarboxylative Fluorination
Xu, Peng,López-Rojas, Priscila,Ritter, Tobias
supporting information, p. 5349 - 5354 (2021/05/05)
Abundant aromatic carboxylic acids exist in great structural diversity from nature and synthesis. To date, the synthetically valuable decarboxylative functionalization of benzoic acids is realized mainly by transition-metal-catalyzed decarboxylative cross couplings. However, the high activation barrier for thermal decarboxylative carbometalation that often requires 140 °C reaction temperature limits both the substrate scope as well as the scope of suitable reactions that can sustain such conditions. Numerous reactions, for example, decarboxylative fluorination that is well developed for aliphatic carboxylic acids, are out of reach for the aromatic counterparts with current reaction chemistry. Here, we report a conceptually different approach through a low-barrier photoinduced ligand to metal charge transfer (LMCT)-enabled radical decarboxylative carbometalation strategy, which generates a putative high-valent arylcopper(III) complex, from which versatile facile reductive eliminations can occur. We demonstrate the suitability of our new approach to address previously unrealized general decarboxylative fluorination of benzoic acids.
Nickel(II)-Catalyzed Addition of Aryl and Heteroaryl Boroxines to the Sulfinylamine Reagent TrNSO: The Catalytic Synthesis of Sulfinamides, Sulfonimidamides, and Primary Sulfonamides
Lo, Pui Kin Tony,Willis, Michael C.
, p. 15576 - 15581 (2021/10/02)
We report a redox-neutral Ni(II)-catalyzed addition of (hetero)aryl boroxines to N-sulfinyltritylamine (TrNSO). The reactions use a catalyst generated from the combination of commercial, air-stable NiCl2·(glyme) and a commercially available bipyridine lig
Chromoselective Synthesis of Sulfonyl Chlorides and Sulfonamides with Potassium Poly(heptazine imide) Photocatalyst
Antonietti, Markus,Guldi, Dirk M.,Markushyna, Yevheniia,Savateev, Aleksandr,Schü?lbauer, Christoph M.,Ullrich, Tobias
supporting information, p. 20543 - 20550 (2021/08/12)
Among external stimuli used to promote a chemical reaction, photocatalysis possesses a unique one—light. Photons are traceless reagents that provide an exclusive opportunity to alter chemoselectivity of the photocatalytic reaction varying the color of incident light. This strategy may be implemented by using a sensitizer capable to activate a specific reaction pathway depending on the excitation light. Herein, we use potassium poly(heptazine imide) (K-PHI), a type of carbon nitride, to generate selectively three different products from S-arylthioacetates simply varying the excitation light and otherwise identical conditions. Namely, arylchlorides are produced under UV/purple, sulfonyl chlorides with blue/white, and diaryldisulfides at green to red light. A combination of the negatively charged polyanion, highly positive potential of the valence band, presence of intraband states, ability to sensitize singlet oxygen, and multi-electron transfer is shown to enable this chromoselective conversion of thioacetates.
New allyldithiocarbimate salts: Synthesis, structure and antifungal activity
Albuini-Oliveira, Nathália M.,Alvarez, Natalia,Ellena, Javier,Guilardi, Silvana,Lima, Marcelo S.,Rubinger, Mayura M. M.,Souza, Rafael A. C.,Tavares, Eder C.,Vidigal, Antonio E. C.,Zacchi, Carlos H. C.,Zambolim, Laercio
, (2020/04/21)
Fifteen new allyldithiocarbimates were prepared from different allylic bromides and various potassium dithiocarbimates, yielding (Z)-2-(methoxycarbonyl)-3-(X-nitrophenyl)allyl-(N-R-sulfonyl)dithiocarbimates (where X = 2, 3 and 4; R = phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl and 4-iodophenyl). These anions were isolated as tetraphenylphosphonium salts and characterized by HRMS, infrared, 1H and 13C NMR spectroscopies. Molecular electrostatic potentials were used to evaluate intermolecular interactions present in the new substances and to explain variations observed on their melting points. Single crystal X-ray diffraction experiments confirmed the Z stereochemistry of the allyldithiocarbimate anions. C–H?O, C–H?N, C–H?S and C–H?π intermolecular interactions in the solid state were studied by X-ray diffraction and Hirshfeld surface analyses. The new compounds inhibited the mycelial growth of various fungi species responsible for severe plant diseases. The allylithiocarbimates were especially active against Botrytis cinerea, with IC50 values as low as 20 μM, being more effective than the active principals of the commercial fungicides Ziram and Mancozeb.
Discovery of Sulfonamide-Derived Agonists of SOS1-Mediated Nucleotide Exchange on RAS Using Fragment-Based Methods
Sarkar, Dhruba,Olejniczak, Edward T.,Phan, Jason,Coker, Jesse A.,Sai, Jiqing,Arnold, Allison,Beesetty, Yugandhar,Waterson, Alex G.,Fesik, Stephen W.
, p. 8325 - 8337 (2020/09/21)
The nucleotide exchange factor Son of Sevenless (SOS) catalyzes the activation of RAS by converting it from its inactive GDP-bound state to its active GTP-bound state. Recently, we have reported the discovery of small-molecule allosteric activators of SOS1 that can increase the amount of RAS-GTP in cells. The compounds can inhibit ERK phosphorylation at higher concentrations by engaging a feedback mechanism. To further study this process, we sought different chemical matter from an NMR-based fragment screen using selective methyl labeling. To aid this process, several Ile methyl groups located in different binding sites of the protein were assigned and used to categorize the NMR hits into different classes. Hit to lead optimization using an iterative structure-based design paradigm resulted in compounds with improvements in binding affinity. These improved molecules of a different chemical class increase SOS1cat-mediated nucleotide exchange on RAS and display cellular action consistent with our prior results.
Primary Sulfonamide Synthesis Using the Sulfinylamine Reagent N-Sulfinyl- O-(tert-butyl)hydroxylamine, t-BuONSO
Davies, Thomas Q.,Hall, Adrian,Skolc, David,Tilby, Michael J.,Willis, Michael C.
supporting information, p. 9495 - 9499 (2020/12/21)
Sulfonamides have played a defining role in the history of drug development and continue to be prevalent today. In particular, primary sulfonamides are common in marketed drugs. Here we describe the direct synthesis of these valuable compounds from organometallic reagents and a novel sulfinylamine reagent, t-BuONSO. A variety of (hetero)aryl and alkyl Grignard and organolithium reagents perform well in the reaction, providing primary sulfonamides in good to excellent yields in a convenient one-step process.
One-pot aerobic oxidative sulfonamidation of aromatic thiols with ammonia by a dual-functional β-MnO2 nanocatalyst
Hayashi, Eri,Yamaguchi, Yui,Kita, Yusuke,Kamata, Keigo,Hara, Michikazu
supporting information, p. 2095 - 2098 (2020/02/26)
High-surface-area β-MnO2 (β-MnO2-HS) nanoparticles could act as effective heterogeneous catalysts for the one-pot oxidative sulfonamidation of various aromatic and heteroaromatic thiols to the corresponding sulfonamides using molecular oxygen (O2) and ammonia (NH3) as respective oxygen and nitrogen sources, without the need for any additives.
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 (2019/07/22)
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.
