- Sequential C-S and S-N Coupling Approach to Sulfonamides
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A one-pot three-component reaction involving nitroarenes, (hetero)arylboronic acids, and potassium pyrosulfite leading to sulfonamides was described. A broad range of sulfonamides bearing different reactive functional groups were obtained in good to excellent yields through sequential C-S and S-N coupling that does not require metal catalysts.
- Chen, Kai,Chen, Wei,Han, Bing,Chen, Wanzhi,Liu, Miaochang,Wu, Huayue
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supporting information
p. 1841 - 1845
(2020/03/04)
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- Probing 2H-Indazoles as Templates for SGK1, Tie2, and SRC Kinase Inhibitors
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The broader and systematic application of a novel scaffold is often hampered by the unavailability of a short and reliable synthetic access. We investigated a new strategy for the design and synthesis of an array of N2-substituted aza-2H-indazole derivatives as potential kinase inhibitors. Guided by a rational ligand alignment approach to qualify the so-far underrepresented aza-2H-indazole scaffold, indazoles were connected at the N2 position with a phenyl spacer and an arylsulfonamide or amide linkage. Initial profiling against a panel of 30 kinases confirmed the in silico predicted selectivity bias. A synthesized focused library of 52 different aza-2H-indazole derivatives showed good initial selective inhibition against SGK1, Tie2, and SRC kinases, with the best representatives having IC50 values in the range of 500 nm. In a comparative computational study, these data were analyzed and rationalized in light of docking studies.
- Schoene, Jens,Gazzi, Thais,Lindemann, Peter,Christmann, Mathias,Volkamer, Andrea,Nazaré, Marc
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p. 1514 - 1527
(2019/08/07)
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- Sulfonamide urease inhibiting agent and preparation method and application thereof
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Benzene sulfonamide compounds have a structural formula as shown in the specification, have great inhibiting effects on urease and can be used for preparation of medicines for treating gastritis, gastric ulcer, lithangiuria and the like. The invention fur
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Paragraph 0037-0041
(2019/01/14)
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- METHODS OF INHIBITING BACTERIAL VIRULENCE AND COMPOUNDS RELATING THERETO
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The present invention relates to compounds and methods for the treatment of bacterial infections. Because their mechanism of action does not involve killing of bacteria or inhibiting their growth, the potential for these compounds to induce drug resistance in bacteria is minimized. Through inhibiting bacterial virulence, the present invention provides a novel means of treating bacterial infections.
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Paragraph 0196
(2017/01/31)
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- Potent Pan-Raf and Receptor Tyrosine Kinase Inhibitors Based on a Cyclopropyl Formamide Fragment Overcome Resistance
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While selective BRafV600E inhibitors have been proven effective clinically, acquired resistance rapidly develops through reactivation of the mitogen-activated protein kinase (MAPK) pathway. Simultaneous targeting of multiple nodes in the pathway offers the prospect of enhanced efficacy as well as reduced potential for acquired resistance. Replacement pyridine group of Y-1 by a cyclopropyl formamide group afforded I-01 as a novel multitargeted kinase inhibitor template. I-01 displayed enzyme potency against Pan-Raf and receptor tyrosine kinases (RTKs). Based on the binding mode of I-01, analogues I-02-I-18 were designed and synthesized. The most promising compound I-16 potently inhibits all subtypes of Rafs with IC50 values of 3.49 (BRafV600E), 8.86 (ARaf), 5.78 (BRafWT), and 1.65 nM (CRaf), respectively. I-16 not only exhibit comparable antiproliferative activities with positive control compounds against HepG2, SW579, MV4-11, and COLO205 cell lines, but also suppress the proliferation of melanoma SK-MEL-2 harboring overexpressed BRafWT with IC50 values of 0.93 μM. The Western blot results for the ERK inhibition in human melanoma SK-MEL-2 cell lines show that I-16 inhibits the proliferation of SK-MEL-2 cell lines without paradoxical activation of ERK, which support the hypothesis that the inhibition of Pan-Raf and RTKs might be a tractable strategy to overcome the resistance of melanoma induced by the therapy with the current selective BRafV600E inhibitors.
- Zhang, Yanmin,Wang, Lu,Zhang, Qing,Zhu, Gaoyuan,Zhang, Zhimin,Zhou, Xiang,Chen, Yadong,Lu, Tao,Tang, Weifang
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p. 1439 - 1452
(2017/06/30)
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- POTENT DUAL BRD4-KINASE INHIBITORS AS CANCER THERAPEUTICS
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Disclosed herein are compounds that are inhibitors of BRD4 and their use in the treatment of cancer. Methods of screening for selective inhibitors of BRD4 are also disclosed. In certain aspects, disclosed are compounds of Formula I-IV.
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Page/Page column 122; 144
(2016/04/26)
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- Design, synthesis and biological activity of N-(3-substituted-phenyl)benzenesulfonamides as selective and reversible LSD1 inhibitors
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Lysine specific demethylase 1?plays a crucial role in regulating histone methylation at residues K4 and K9 on histone H3 and over-expresses in a variety of cancers. Here we designed, synthesized and evaluated a series of N-(3-substituted-phenyl)benzenesul
- Zha, Xiaoming,Wu, Liming,Xu, Siyuan,Zou, Fangxia,Xi, Jiayue,Ma, Tianfang,Liu, Rongfeng,Liu, Yu-Chih,Deng, Dawei,Gu, Yueqing,Zhou, Jinpei,Lan, Fei
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p. 2822 - 2831
(2016/11/09)
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- Synthesis and characterization of SiO2-supported ruthenium complexes containing aromatic sulfonamides: As catalysts for transfer hydrogenation of acetophenone
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3-Amino-N-aryl-benzenesulfonamides (1-3) were successfully synthesized by the reaction of m-phenylenediamine and various benzenesulfonyl chlorides. Then, a series of ruthenium complexes (4-6) were prepared from the reaction of [RuCl2(p-cymene)]2 and 1-3. Finally, SiO 2-supported Ru(ii) complexes (7-9) were prepared by an impregnation method. The synthesized compounds and materials were characterized by different methods such as NMR, FT-IR, TG/DTA, nitrogen adsorption-desorption (BET), SEM and EDX. Also, the solid state structures of 4-6 were determined by single-crystal X-ray diffraction. 4-9 were used as catalysts for the transfer hydrogenation of acetophenone. 4-9 showed good catalytic activity and so the effects of the different groups were also examined. For the transfer hydrogenation of acetophenone, 7-9 had similar activity to 4-6. However, the longer lifetime of 7-9 makes them more advantageous than the non-supported catalysts (4-6) in terms of catalytic cycle. Therefore, the effect of SiO 2 was investigated as a catalyst and the results show that excess silicon(iv) oxide was a surprisingly active catalyst for the hydrogenation of acetophenone under these conditions.
- Dayan, Serkan,Kalaycioglu, Nilguen Oezpozan,Dayan, Osman,Oezdemir, Namik,Dincer, Muharrem,Bueyuekguengoer, Orhan
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p. 4957 - 4969
(2013/04/10)
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- Copper-catalyzed N-arylation of sulfonamides with aryl bromides under mild conditions
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This Letter describes a copper catalyzed sulfonamide coupling reaction with aryl bromides to form N-aryl sulfonamides under mild conditions, including the first examples of Cu-catalyzed sulfonamide coupling at room temperature. The reaction protocol tolerates a broad range of substrates including a variety of primary and secondary sulfonamides and challenging heteroaryl bromides such as 2-bromothiazole.
- Wang, Xiang,Guram, Anil,Ronk, Michael,Milne, Jacqueline E.,Tedrow, Jason S.,Faul, Margaret M.
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supporting information; experimental part
p. 7 - 10
(2012/01/06)
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- Binding of sulfonyl-containing arylalkylamines at human 5-HT6 serotonin receptors
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Various sulfonyl-containing compounds (e.g. sulfonamides, sulfones) bind at human 5-HT6 serotonin receptors, but it has been difficult relating the binding mode(s) of such agents to one another, even though many possess a common SO2 moiety, to identify a common pharmacophore model(s). On the basis of the hypothesis that an ergoline-type conformation might be important for the binding of some sulfonamide-containing arylalkylamines, we prepared for examination at h5-HT6 receptors a series of compounds, including phenylethylamines 6, pyrroloethylamine 7, and phenylpiperazines 9. The results (with Ki values ranging from about 1 nM to > 1000 nM) suggest that many of these agents likely bind in a related fashion, and structure-affinity studies indicate that the benzenesulfonamide portion of the phenylethylamine and phenylpiperazine analogues can be "reversed", abbreviated to a sulfone, and moved to an adjacent position with relatively little impact on affinity. Although a benzenesulfonamide (or related arylsulfonamide) group might be common to various 5-HT6 ligands, there appears to be some latitude with regard to the specific constitution and location of the sulfonamide moiety even within the same arylalkylamine structural framework. A pharmacophore model is presented to account for some of the current findings.
- Sikazwe, Donald,Bondarev, Mikhail L.,Dukat, Ma?gorzata,Rangisetty, Jagadeesh B.,Roth, Bryan L.,Glennon, Richard A.
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p. 5217 - 5225
(2007/10/03)
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