158038-67-6Relevant articles and documents
Mechanistic Insight Enables Practical, Scalable, Room Temperature Chan-Lam N-Arylation of N-Aryl Sulfonamides
Vantourout, Julien C.,Li, Ling,Bendito-Moll, Enrique,Chabbra, Sonia,Arrington, Kenneth,Bode, Bela E.,Isidro-Llobet, Albert,Kowalski, John A.,Nilson, Mark G.,Wheelhouse, Katherine M. P.,Woodard, John L.,Xie, Shiping,Leitch, David C.,Watson, Allan J. B.
, p. 9560 - 9566 (2018)
Sulfonamides are profoundly important in pharmaceutical design. C-N cross-coupling of sulfonamides is an effective method for fragment coupling and structure-activity relationship (SAR) mining. However, cross-coupling of the important N-arylsulfonamide pharmacophore has been notably unsuccessful. Here, we present a solution to this problem via oxidative Cu-catalysis (Chan-Lam cross-coupling). Mechanistic insight has allowed the discovery and refinement of an effective cationic Cu catalyst to facilitate the practical and scalable Chan-Lam N-arylation of primary and secondary N-arylsulfonamides at room temperature. We also demonstrate utility in the large scale synthesis of a key intermediate to a clinical hepatitis C virus treatment.
Synthesis and evaluation of novel S-benzyl- and S-alkylphthalimide- oxadiazole -benzenesulfonamide hybrids as inhibitors of dengue virus protease
Batool, Farwa,Hamdani, Syeda Shamila,Hameed, Shahid,Khan, Bilal Ahmad,Mughal, Ehsan Ullah,Saeed, Muhammad,Saleem, Hafiza Nosheen
, (2020/02/15)
Direct acting antiviral drugs (DAADs) are becoming therapeutics of choice for the treatment of viral infections. Successful development of anti HIV and HCV drugs by targeting the viral proteases has provided impetus for discovering newer DAADs. Dengue virus (DENV) protease, which is composed of two nonstructural proteins, NS2B and NS3pro, can be likewise exploited for discovering new anti-dengue therapeutics. In this study, we have linked together two pharmaceutically interesting motifs, namely 1,3,4-oxadiazole and benzenesulfonamide in two alternative series to develop novel S-benzylated and S-alkylphthalimidated hybrids. For the first series of hybrids, 4-aminobenzoic acid (1) was reacted with substituted benzenesulfonyl chlorides via its amino group, whereas the carboxylic acid side was elaborated to sulfonamido-1,3,4-oxadiazole-2-thiols (6a/b) in three steps. At this stage, the intermediates 6a/b were bifurcated to either S-alkylphthalimidated (8a-j) or S-benzylated (9a-c) hybrids by reacting with corresponding halides. For the alternative series of hybrids, the carboxylic acid group of probenecid (10) was similarly elaborated to sulfonamido-1,3,4-oxadiazole-2-thiols (13), and diverged to S-alkylphthalimidated (14a-f) and S-benzylated hybrids (15a-e). Bioactivity assays demonstrated that 8g and 8h are the most potent inhibitors among the synthesized analogs, exhibiting the IC50 values of 13.9 μM and 15.1 μM, respectively. Computational assessment predicted the binding of the inhibitors at an allosteric site developed in the open conformation of DENV2 NS2B/NS3pro. Taken together these findings point out that the synthesized hybrid inhibitors possess a great potential for further antiviral drug development.
Preparation method of sulfamide compound
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Paragraph 0038-0041, (2020/06/02)
The invention belongs to the technical field of organic chemistry, and particularly relates to a preparation method of a sulfamide compound, wherein the structure of the sulfamide compound synthesizedby the method is characterized and confirmed by H NMR and C NMR. The method comprises the following steps: in an organic solvent, carrying out a reaction on an aryl diazonium salt, a sulfur dioxide solid complex and an aryl nitroso compound in the presence of a reducing agent under a heating condition, wherein the diazonium salt and the sulfur dioxide solid complex act to generate aryl sulfonyl free radicals, and then the aryl nitroso compound is attacked; and reducing the generated hydroxylamine to obtain the sulfamide compound. The preparation method of the compound has the advantages of mild conditions, simplicity, high efficiency, no need of catalysts, no need of pre-synthesis of sulfonyl chloride or sodium sulfonate reagents, wide substrate application range, strong functionalgroup compatibility, convenience in separation and purification, and excellent industrial and medicinal chemical application values.
Nitrosoarenes as Nitrogen Source for Generation of Sulfonamides with the Insertion of Sulfur Dioxide under Metal-Free Conditions?
Wang, Xuefeng,Lin, Yanmei,Liu, Jin-Biao,He, Fu-Sheng,Kuang, Yunyan,Wu, Jie
supporting information, p. 1098 - 1102 (2020/07/06)
A metal-free reaction of nitrosoarenes, aryldiazonium tetrafluoroborates, and sulfur dioxide under mild conditions is developed, giving rise to sulfonamides in moderate to good yields. This transformation proceeds efficiently at room temperature in the presence of cyclohexa-1,4-diene with a broad reaction scope. Good functional group compatibility is observed, including cyano, halo, and ester. A plausible mechanism involving a radical process with the insertion of sulfur dioxide is proposed, and cyclohexa-1,4-diene serves as the reductant during the transformation.
Practical heterogeneous photoredox/nickel dual catalysis for C-N and C-O coupling reactions
Liu, Yi-Yin,Liang, Dong,Lu, Liang-Qiu,Xiao, Wen-Jing
supporting information, p. 4853 - 4856 (2019/05/02)
Efficient C-N and C-O coupling reactions of aryl halides with amines and alcohols have been developed by using the strategy of heterogeneous visible light photoredox and nickel dual catalysis. Obviously, the joint use of inexpensive and bench-stable CdS and nickel salts, together with mild reaction conditions, makes these two transformations attractive for the synthetic community. This heterogeneous dual catalysis system also proved to be successful in the ligand-free catalytic hydroxylation of aryl bromide with water as a nucleophile. The practicality of this protocol is further emphasized by the scaled-up reaction and the reusability of heterogeneous photocatalysts.
Copper-catalyzed redox coupling of nitroarenes with sodium sulfinates
Liu, Saiwen,Chen, Ru,Zhang, Jin
, (2019/05/02)
A simple copper-catalyzed redox coupling of sodium sulfinates and nitroarenes is described. In this process, abundant and stable nitroarenes serve as both the nitrogen sources and oxidants, and sodium sulfinates act as both reactants and reductants. A variety of aromatic sulfonamides were obtained in moderate to good yields with broad substrate scope. No external additive is employed for this kind of transformation.
Copper-catalyzed cross-coupling of chloramine salts and arylboronic acids in water: A green and practical route to N-arylsulfonamides
Ouyang, Banlai,Zheng, Yanxia,Liu, Yi,Liu, Fei,Yao, Juying,Peng, Yiyuan
, p. 3694 - 3698 (2018/09/14)
A green and practical method for the synthesis of N-arylsulfonamides from chloramine salts and arylboronic acids is herein developed. The reaction proceeds readily in the presence of 5 mol% of CuI and 2.5 equiv. K2CO3 in water at room temperature, generating a variety of N-arylsulfonamides in moderate to good yields with good functional group tolerance.
Development and validation of a docking-based virtual screening platform for the identification of new lactate dehydrogenase inhibitors
Granchi, Carlotta,Capecchi, Alice,Del Frate, Gianluca,Martinelli, Adriano,Macchia, Marco,Minutolo, Filippo,Tuccinardi, Tiziano
, p. 8772 - 8790 (2015/09/01)
The human muscle isoform of lactate dehydrogenase (hLDH5) is one of the key enzymes of the glycolytic process. It is overexpressed in metastatic cancer cells and is linked to the vitality of tumors in hypoxic conditions. With the aim of identifying new hLDH5 inhibitors, a fully automated docking-based virtual screening platform was developed by considering different protein conformations and the consensus docking strategy. In order to verify the reliability of the reported platform, a small database of about 10,000 compounds was filtered by using this method, and the top-ranked compounds were tested for their hLDH5 inhibition activity. Enzymatic assays revealed that, among the ten selected compounds, two proved to efficiently inhibit enzyme activity with IC50 values in the micromolar range. These results demonstrate the validity of the methodologies we followed, encouraging the application of larger virtual screening studies and further refinements of the platform. Furthermore, the two active compounds herein described may be considered as interesting leads for the development of new and more efficient LDH inhibitors.
Iron-catalyzed N -arylsulfonamide formation through directly using nitroarenes as nitrogen sources
Zhang, Weixi,Xie, Junyao,Rao, Bin,Luo, Meiming
, p. 3504 - 3511 (2015/04/14)
One-step, catalytic synthesis of N-arylsulfonamides via the construction of N-S bonds from the direct coupling of sodium arylsulfinates with nitroarenes was realized in the presence of FeCl2 and NaHSO3 under mild conditions. In this process, stable and readily available nitroarenes were used as nitrogen sources, and NaHSO3 acted as a reductant to provide N-arylsulfonamides in good to excellent yields. A broad range of functional groups were very well-tolerated in this reaction system. In addition, mechanistic studies indicated that the N-S bond might be generated through direct coupling of nitroarene with sodium arylsulfinate prior to the reduction of nitroarenes by NaHSO3. Accordingly, a reaction mechanism involving N-aryl-N-arenesulfonylhydroxylamine as an intermediate was proposed.
Exploiting the narrow gap of rearrangement between the substituents in the vicinal disubstitution reactions of diaryliodonium salts with pyridine N-sulfonamidates
Wang, Yong,Li, Ming,Wen, Lirong,Jing, Peng,Su, Xiang,Chen, Chao
, p. 751 - 763 (2015/02/19)
The vicinal disubstitution reactions of diaryliodonium salts with pyridine N-sulfonamidates to give o-pyridinium anilines were fully examined. A reaction pathway of N-arylation occurring at the amidate group followed by a radical rearrangement is proposed. The electronic effects of various substituents in this radical rearrangement were investigated.
