1899-94-1Relevant academic research and scientific papers
Multiprotein Dynamic Combinatorial Chemistry: A Strategy for the Simultaneous Discovery of Subfamily-Selective Inhibitors for Nucleic Acid Demethylases FTO and ALKBH3
Das, Mohua,Yang, Tianming,Dong, Jinghua,Prasetya, Fransisca,Xie, Yiming,Wong, Kendra H. Q.,Cheong, Adeline,Woon, Esther C. Y.
, p. 2854 - 2867 (2018)
Dynamic combinatorial chemistry (DCC) is a powerful supramolecular approach for discovering ligands for biomolecules. To date, most, if not all, biologically templated DCC systems employ only a single biomolecule to direct the self-assembly process. To expand the scope of DCC, herein, a novel multiprotein DCC strategy has been developed that combines the discriminatory power of a zwitterionic “thermal tag” with the sensitivity of differential scanning fluorimetry. This strategy is highly sensitive and could differentiate the binding of ligands to structurally similar subfamily members. Through this strategy, it was possible to simultaneously identify subfamily-selective probes against two clinically important epigenetic enzymes: FTO (7; IC50=2.6 μm) and ALKBH3 (8; IC50=3.7 μm). To date, this is the first report of a subfamily-selective ALKBH3 inhibitor. The developed strategy could, in principle, be adapted to a broad range of proteins; thus it is of broad scientific interest.
Meta -Non-flat substituents: A novel molecular design to improve aqueous solubility in small molecule drug discovery
Ichikawa, Yuki,Hiramatsu, Michiaki,Mita, Yusuke,Makishima, Makoto,Matsumoto, Yotaro,Masumoto, Yui,Muranaka, Atsuya,Uchiyama, Masanobu,Hashimoto, Yuichi,Ishikawa, Minoru
supporting information, p. 446 - 456 (2021/01/29)
Aqueous solubility is a key requirement for small-molecule drug candidates. Here, we investigated the regioisomer-physicochemical property relationships of disubstituted benzenes. We found that meta-isomers bearing non-flat substituents tend to possess the lowest melting point and the highest thermodynamic aqueous solubility among the regioisomers. The examination of pharmaceutical compounds containing a disubstituted benzene moiety supported the idea that the introduction of a non-flat substituent at the meta position of a benzene substructure would be a promising approach for medicinal chemists aiming to improve the thermodynamic aqueous solubility of drug candidates, even though it might not be universally effective. This journal is
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.
Electrochemically generatedN-iodoaminium species as key intermediates for selective methyl sulphonylimination of tertiary amines
Huang, Binbin,Yang, Chao,Zhou, Jia,Xia, Wujiong
supporting information, p. 5010 - 5013 (2020/05/18)
Reported herein is a straightforward protocol for approachingN-sulphonylamidinesviaan electricity-driven, iodine-mediated cross dehydrogenative condensation (CDC) between sulphonamides and tertiary amines, which features exclusive N-CH3selectivity for the amine partners. Mechanistic studies indicate that anin situgeneratedN-iodoaminium species serves as the key intermediate.
Manganese-Catalyzed N-Alkylation of Sulfonamides Using Alcohols
Reed-Berendt, Benjamin G.,Morrill, Louis C.
, p. 3715 - 3724 (2019/03/30)
An efficient manganese-catalyzed N-alkylation of sulfonamides has been developed. This borrowing hydrogen approach employs a well-defined and bench-stable Mn(I) PNP pincer precatalyst, allowing benzylic and simple primary aliphatic alcohols to be employed as alkylating agents. A diverse range of aryl and alkyl sulfonamides undergoes mono-N-alkylation in excellent isolated yields (32 examples, 85% average yield).
Highly Chemoselective NH- and O-Transfer to Thiols Using Hypervalent Iodine Reagents: Synthesis of Sulfonimidates and Sulfonamides
Tota, Arianna,St John-Campbell, Sahra,Briggs, Edward L.,Estévez, Gala Ogalla,Afonso, Michelle,Degennaro, Leonardo,Luisi, Renzo,Bull, James A.
supporting information, p. 2599 - 2602 (2018/05/22)
Aryl thiols can be selectively converted to sulfonimidates or sulfonamides with three new S-X connections being made selectively in one pot. Using hypervalent iodine reagents in the presence of ammonium carbamate, NH- and O-groups are transferred under mild and practical conditions. Reducing the loading of ammonium carbamate changed the product distribution, converting the sulfonimidate to the sulfonamide. Studies into the possible intermediate species are presented, suggesting that multiple pathways may be possible via sulfinate esters, or related intermediates, with each species forming the same products.
N-acyl sulfamide FBPase inhibitor, preparation method thereof, drug composition and application
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Paragraph 2483; 2485; 2486, (2017/09/08)
The invention discloses an N-acryl sulfamide FBPase inhibitor of a novel structure, and a preparation method thereof, a drug composition and an application, and particularly relates to an N-acryl sulfamide FBPase inhibitor shown in the formula I, a salt thereof for medicine, a preparation method, a composition comprising one or more compounds, an application of the compound in preparing the FBPase inhibitor or a drug for treating FBPase-related diseases, and an application in preparing a drug for preventing and/or treating diabetes. The formula is shown in the description.
Cu(II)-catalyzed decarboxylation/elimination of N-arylsulfonyl amino acids to primary aryl sulfonamides
Zhou, Liandi,Li, Xiaokang,Liu, Wei,Zhao, Yongli,Chen, Junmin
, p. 1299 - 1306 (2016/08/16)
A novel protocol for CuO-catalyzed decarboxylation/elimination of N-arylsulfonyl amino acids was developed. It is the first example of using an accessible amino acid as an ammonia synthetic equivalent for the synthesis of primary aryl sulfonamides via oxidative decarboxylation/elimination reactions. The present protocol shows excellent functional group tolerance and provides an efficient method for the synthesis of primary aryl sulfonamides in excellent yields.
A general iodine-mediated synthesis of primary sulfonamides from thiols and aqueous ammonia
Feng, Jian-Bo,Wu, Xiao-Feng
supporting information, p. 6951 - 6954 (2016/07/30)
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.
Sulfonamide formation from sodium sulfinates and amines or ammonia under metal-free conditions at ambient temperature
Yang, Kai,Ke, Miaolin,Lin, Yuanguang,Song, Qiuling
, p. 1395 - 1399 (2015/03/18)
A novel, practical and highly efficient method for the construction of a variety of sulfonamides mediated by I2 was demonstrated. The reaction proceeds readily at room temperature using a variety of sodium sulfinates and amines or ammonia in water in a metal-, base-, ligand-, or additive-free protocol. Primary, secondary and tertiary sulfonamides were obtained in good to excellent yields with a broad range of functional group tolerability. This journal is
