- Discovery of N-(3,4-Dimethylphenyl)-4-(4-isobutyrylphenyl)-2,3,3a,4,5,9b-hexahydrofuro[3,2- c]quinoline-8-sulfonamide as a Potent Dual MDM2/XIAP Inhibitor
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Murine double minute 2 (MDM2) and X-linked inhibitor of apoptosis protein (XIAP) are important cell survival proteins in tumor cells. As a dual MDM2/XIAP inhibitor reported previously, compound MX69 has low potency with an IC50 value of 7.5 μM against an acute lymphoblastic leukemia cell line EU-1. Herein, we report the structural optimization based on the MX69 scaffold, leading to the discovery of a 25-fold more potent analogue 14 (IC50 = 0.3 μM against EU-1). We demonstrate that 14 maintains its mode of action by dual targeting of MDM2 and XIAP through inducing MDM2 protein degradation and inhibiting XIAP mRNA translation, respectively, which resulted in cancer cell growth inhibition and cell death. The results strongly suggest that the scaffold based on 14 is promising for further optimization to develop a new therapeutic agent for leukemia and possibly other cancers where MDM2 and XIAP are dysregulated.
- Wu, Zhongzhi,Gu, Lubing,Zhang, Sicheng,Liu, Tao,Lukka, Pradeep B.,Meibohm, Bernd,Bollinger, John C.,Zhou, Muxiang,Li, Wei
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p. 1930 - 1950
(2021/03/01)
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- Synthesis of magnetic chitosan supported metformin-Cu(II) complex as a recyclable catalyst for N-arylation of primary sulfonamides
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The application of chitosan, which has received much attention as a natural polymer and effective support, has many advantages such as biodegradability and biocompatibility. In this study, the immobilization of a copper complex on the magnetic chitosan bearing metformin ligand has been developed through immobilizing structurally defined metformin with long tail of (3-chloropropyl)trimethoxysilane (TMOS). The synthesized Fe3O4-chitosan@metformin-Cu(II) complex (Fe3O4-CS@Met-Cu(II)) was used as an effective, reusable and magnetic catalyst in the N-arylation of different derivatives of primary sulfonamides with arylboronic acids in ethanol. The primary sulfonamides were prepared from the reaction of sulfonyl chlorides with sodium cyanate in water under ultrasonic irradiation. Utilizing a wide variety of substrates in EtOH as a green solvent, high yields of the primary and secondary sulfonamides, easy work-up along with the excellent recovery and reusability of the catalyst, make this process a simple, economic and environmentally benign method. The synthesized Fe3O4-CS@Met-Cu(II) was characterized using various techniques such as XRD (X-ray diffraction), EDS (energy-dispersive X-ray spectroscopy), elemental mapping, TEM (transmission electron microscopy), FESEM (field emission scanning electron microscopy), VSM (vibrating sample magnetometer), ICP-MS (inductively coupled plasma mass spectroscopy), TGA (thermogravimetric analysis) and FT-IR (Fourier-transform infrared spectroscopy) analyses. The catalyst can be recycled and reused 5 times with no considerable loss of catalytic activity.
- Ahmadpoor, Fatemeh,Nasrollahzadeh, Mahmoud,Nezafat, Zahra,Pakzad, Khatereh
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- Sulphonamidic Groups as Electron-Withdrawing Units in Ureido-Based Anion Receptors: Enhanced Anion Complexation versus Deprotonation
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A sulphonamidic moiety was utilized as an electron-withdrawing group for enhancement of anion complexation features of urea-based receptors. A series of receptors varying in acidity of sulphonamidic and urea NH groups was synthesized and thoroughly tested. The individual complexation properties reflect deprotonation/complexation equilibrium in a given molecule as a function of the substitution. The receptors containing electron-donating groups in conjugation to the sulphonamidic moiety showed higher association constants towards H2PO4? and carboxylate anions, while those containing electron-withdrawing groups inclined to deprotonation of sulphonamidic NH. The deprotonation issue can be avoided by alkylation at the early step of receptor synthesis or it can be utilized for insertion of suitable groups that enable its anchoring on various substrates to form more elaborated receptor structures.
- ?imková, Ludmila,Císa?ová, Ivana,Cu?ínová, Petra,Ludvík, Ji?í,Sykora, Jan,Salvadori, Karolína
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p. 1401 - 1411
(2020/08/05)
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- Arylation and alkenylation of activated alkyl halides using sulfonamides
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A variety of quaternary aryl amino acid derivatives can be synthesised using tandem SN2/Smiles rearrangement chemistry involving aryl sulfonamides and α-chloro carbonyl compounds. The reaction harnesses a sulfur dioxide extrusion pathway to construct a C-N and C-Caryl bond under simple conditions with no requirement for organometallics or transition metal catalysts. The reaction is also successful for alkenyl sulfonamides, producing sterically congested quaternary alkene amino acid derivatives.
- Greaney, Michael F.,Johnson, Stuart,Kovács, Ervin
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supporting information
p. 3222 - 3224
(2020/03/23)
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- A Cascade Reaction of Michael Addition and Truce-Smiles Rearrangement to Synthesize Trisubstituted 4-Quinolone Derivatives
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A novel transition-metal-free cascade reaction to synthesize 4-quinolone derivatives has been demonstrated. Michael addition and Truce-Smiles rearrangement are included in this protocol, providing a broad scope of 4-quinolones in moderate-to-excellent yields. This work serves as an example of the use of sulfonamides through Truce-Smiles rearrangement to build heterocyclic compounds under mild conditions.
- Xie, Caixia,Yang, Di,Wang, Xinfeng,Ma, Chen
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p. 14937 - 14944
(2020/12/02)
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- Metal-Free β-Amino Alcohol Synthesis: A Two-step Smiles Rearrangement
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A novel method for the synthesis of β-amino alcohols has been demonstrated under mild reaction conditions with a broad scope via a two-step Smiles rearrangement. What is more, theoretical calculations have been performed to confirm the rationality of the mechanism. The method has been proved to be notably effective for N-arylated amino alcohols, which are difficult to synthesize by traditional methods.
- Yang, Di,Xie, Cai-Xia,Wu, Xiao-Tian,Fei, Luo-Ran,Feng, Lei,Ma, Chen
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supporting information
p. 14905 - 14915
(2020/11/13)
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- Metal-free one-pot synthesis of N-arylsulfonamides from nitroarenes and sodium sulfinates in an aqueous medium
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A metal-free one-pot two-step synthesis of sulfonamides from readily available nitroarenes and sodium arylsulfinates in a mixture of methanol and water has been developed. In this procedure, the aryl amines were produced in situ by the reduction of nitroarenes mediated by diboronic acid, and then coupled with sodium arylsulfinates in the presence of iodine. A series of N-arylsulfonamides with various functional groups were obtained in moderate to good yields under the optimal reaction conditions. In addition, this one-pot process is applicable for gram-scale synthesis.
- Jiang, Xiaolan,Zhang, Kaili,Zhao, Rongrong,Bai, Die,Wang, Jinlong,Li, Binbin,Liu, Qixing,Zhou, Haifeng
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supporting information
(2020/09/10)
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- Synthesis, Characterization, and Reactivity of an Ethynyl Benziodoxolone (EBX)-Acetonitrile Complex
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The synthesis of a crystalline ethynyl-1,2-benziodoxol-3(1H)-one (EBX)-acetonitrile complex is described. EBX has been widely used as an active species for a variety of reactions; however, its high instability has so far prevented its isolation. The EBX-acetonitrile is self-assembled into a double-layered honeycomb structure through weak hypervalent iodine secondary interactions and hydrogen bonding. The N-ethynylation of a variety of sulfonamides using the EBX-acetonitrile complex as a substrate under mild conditions is also described.
- Yudasaka, Masaharu,Shimbo, Daisuke,Maruyama, Toshifumi,Tada, Norihiro,Itoh, Akichika
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supporting information
p. 1098 - 1102
(2019/05/16)
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- Lewis Base Promoted, Direct 1,4-Conjugate Addition to Quinone Imine Ketals: Efficient Access to Unsymmetrical Diaryl Sulfones
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An alternative approach with eco-friendliness and high efficiency for the preparation of unsymmetrical diaryl sulfones has been developed. The strategy takes advantage of the reaction of sulfonyl hydrazides with quinone imine ketals catalyzed by DABCO (triethylenediamine) in ethanol. This transformation proceeds via a Lewis base promoted, direct 1,4-conjugate addition/sulfonylation/alcohol elimination reaction sequence. The protocol provides an efficient approach to access an array of diverse unsymmetrical diaryl and heterodiaryl sulfones, aryl alkyl sulfones and aryl vinyl sulfones in good to excellent yields.
- Liu, Teng,Liu, Jianjun,Shen, Xianfu,Xu, Jianbin,Nian, Beifang,He, Ni,Zeng, Shunqun,Cheng, Feixiang
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p. 1365 - 1376
(2019/03/08)
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- A palladium-catalyzed regiocontrollable hydroarylation reaction of allenamides with B2pin2/H2O
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A novel palladium-catalyzed regiocontrollable hydroarylation reaction of allenamides with B2pin2/H2O has been disclosed. H2O as an ideal hydrogen source was activated by B2pin2 to furnish allylamines or enamines with a broad functional group tolerance. The regioselectivity for both of the two products was up to 99:1 for most of the examples, which was achieved by adjusting the addition order of the catalyst and iodobenzene derivatives. The tentative investigation of the mechanism proved the reaction to be a non-radical process and the deuterium-labeled experiments indicated that the hydrogen was from H2O.
- Cui, Jie,Meng, Long,Chi, Xiaochen,Liu, Qing,Zhao, Pingping,Zhang, Dao-Peng,Chen, Lei,Li, Xinjin,Dong, Yunhui,Liu, Hui
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supporting information
p. 4355 - 4358
(2019/04/26)
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- Novel analogs of sulfasalazine as system xc ? antiporter inhibitors: Insights from the molecular modeling studies
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System xc ? (Sxc ?), a cystine-glutamate antiporter, is established as an interesting target for the treatment of several pathologies including epileptic seizures, glioma, neurodegenerative diseases, and multiple sclerosis. Erastin, sorafenib, and sulfasalazine (SSZ) are a few of the established inhibitors of Sxc ?. However, its pharmacological inhibition with novel and potent agents is still very much required due to potential issues, for example, potency, bioavailability, and blood–brain barrier (BBB) permeability, with the current lead molecules such as SSZ. Therefore, in this study, we report the synthesis and structure–activity relationships (SAR) of SSZ derivatives along with molecular docking and dynamics simulations using the developed homology model of xCT chain of Sxc ? antiporter. The generated homology model attempted to address the limitations of previously reported comparative protein models, thereby increasing the confidence in the computational modeling studies. The main objective of the present study was to derive a suitable lead structure from SSZ eliminating its potential issues for the treatment of glioblastoma multiforme (GBM), a deadly and malignant grade IV astrocytoma. The designed compounds with favorable Sxc ? inhibitory activity following in vitro Sxc ? inhibition studies, showed moderately potent cytotoxicity in patient-derived human glioblastoma cells, thereby generating potential interest in these compounds. The xCT-ligand model can be further optimized in search of potent lead molecules for novel drug discovery and development studies.
- Patel, Dhavalkumar,Kharkar, Prashant S.,Gandhi, Neha S.,Kaur, Ekjot,Dutt, Shilpee,Nandave, Mukesh
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p. 758 - 777
(2019/06/24)
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- Nitrene Insertion into Aromatic and Benzylic C?H Bonds Catalyzed by Copper Complexes of Fluorinated Bis- and Tris(pyrazolyl)borates
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Fluorinated bis- and tris(pyrazolyl)boratocopper complexes catalyze the nitrene insertion to C?H bonds of aromatic hydrocarbons efficiently producing amination products in good to excellent yields at room temperature. Imidoiodanes, PhI=NTs (Ts=p-toluenesulfonyl) and PhI=NNs (Ns=p-nitrophenylsulfonyl) serve as the nitrene source. The bis(pyrazolyl)borate catalyst [H2B(3,5-(CF3)2Pz)2]Cu(NCMe) with PhI=NNs produced the arene C?H functionalized product of mesitylene in 87 % yield with only trace amounts of benzylic C?H insertion. The use of [H2B(3,5-(CF3)2-4-(NO2)Pz)2]Cu(NCMe) that has an even weakly donating pyrazolate generated the arene C?H insertion product exclusively. The tris(pyrazolyl)borate complex [HB(3,5-(CF3)2Pz)3]Cu(NCMe), in contrast, generated the benzylic amination product from mesitylene and PhI=NNs in 82 % yield with only very minor amounts of arene C?H functionalization. DFT calculations suggest that Cu-nitrene moiety generated from [HB(3,5-(CF3)2Pz)3]Cu(NCMe) and PhI=NNs activates the benzylic C?H bond of mesitylene via a hydrogen atom abstraction (HAA) followed by a radical rebound (RR) pathway, whereas the functionalization of sp2 C?H bonds of mesitylene by [H2B(3,5-(CF3)2Pz)2]Cu(NNs) ensues possibly via a nitrene addition to the arene core.
- Ponduru, Tharun T.,Sun, Zhicheng,Cundari, Thomas R.,Rasika Dias
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p. 4966 - 4973
(2019/11/05)
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- Regioselective C-H Amidation of (Alkyl)arenes by Iron(II) Catalysis
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A nondirected amidation reaction of aromatic C-H bond was developed under iron(II) catalysis, using sulfonyl azides as the nitrogen source. The reaction displayed a broad substrate scope and good regioselectivities in the aspects of aromatic ring vs alkyl
- Ding, Yao,Zhang, Shen-Yuan,Chen, Yu-Chen,Fan, Shuai-Xin,Tian, Jie-Sheng,Loh, Teck-Peng
-
supporting information
p. 2736 - 2739
(2019/04/16)
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- Synthesis of 3-Amino-1-benzothiophene-1,1-diones by Alkyne Directed Hydroarylation and 1/N→3/C-Sulfonyl Migration
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A completely regioselective and highly stereoselective palladium-catalyzed intramolecular hydroarylation of arenesulfonyl ynamines to benzothiazoles was developed. The presence of an electron-withdrawing group on the triple bond of the sulfonyl ynamine was crucial for the success of the reaction and our mechanistic studies suggest an alkyne-directed 5-exo-dig cyclization pathway. The products easily underwent photoinduced rearrangement to 3-amino-1-benzothiophene-1,1-diones (up to 35 % yields after two steps).
- Bernar, Ivan,Blanco-Ania, Daniel,Stok, Sophie J.,Sotorríos, Lia,Gómez-Bengoa, Enrique,Rutjes, Floris P. J. T.
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supporting information
p. 5435 - 5444
(2018/10/20)
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- Rearrangement Reaction Based on the Structure of N-Fluoro- N-alkyl Benzenesulfonamide
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A novel rearrangement reaction based on the structure of N-fluoro-N-alkyl benzenesulfonamide was developed. The reaction proceeded readily at 50 °C in formic acid and generated a variety of benzenesulfonamides and aldehydes or ketones simultaneously. The reaction mechanism is believed to be a concerted mechanism that consist of 1,2-aryl migration with the departure of fluorine anion via an SN2 mechanism. This rearrangement reaction features an interesting reaction mechanism, mild reaction conditions, simple operations, and a broad substrate scope.
- Wang, Han-Ying,Pu, Xiao-Qiu,Yang, Xian-Jin
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p. 13103 - 13110
(2018/10/20)
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- Palladium-catalyzed desulfitative arylation of sulfonamides with sodium arylsulfinates
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A Pd(II)-catalyzed desulfitative arylation protocol between sulfonamides and sodium arylsulfinates was herein reported. The direct arylation reaction was successfully achieved by a Pd(II)/Ag(I)-mediated system without participation of any external ligands with a release of SO2. And different N-aryl sulfonamides were obtained readily in up to 86% yields, exhibiting good functional groups tolerance (25 examples).
- Zhao, Zijian,Lian, Yan,Zhao, Chang,Wang, Bing
-
supporting information
p. 1436 - 1442
(2018/06/01)
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- New method for synthesizing (S)-metolachlor and its analogue
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The invention relates to a new method for preparing (S)-metolachlor and its analogue. The (S)-metolachlor is taken as an example: the (S)-metolachlor is prepared from 2-methyl-6-ethylaniline and R-propylene glycol monomethyl ether through a four-step reaction. The method has the advantages of cheap and easily available raw materials, mild reaction conditions, high efficiency and very simple separation process.
- -
-
Paragraph 0037-0040; 0043; 0044
(2020/03/12)
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- Palladium-Catalyzed Regioselective Synthesis of 3-Arylindoles from N-Ts-Anilines and Styrenes
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A Pd-catalyzed intermolecular oxidative annulation between N-Ts-anilines and styrenes was developed. This method offers a straightforward and robust approach to a wide range of 3-arylindoles using readily available starting materials with good functional-group tolerance and high regioselectivity and efficiency. Further elaboration of the products obtained from this process provided access to highly functionalized and structurally diverse indoles, for example, 3-(indol-3-yl)carbazoles, 1,9-dihydropyrrolo-[2,3-b]carbazoles, and 3′-aryl-3,5′-biindoles.
- Youn, So Won,Ko, Tae Yun,Jang, Young Ho
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supporting information
p. 6636 - 6640
(2017/05/29)
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- Optimized Synthetic Route for Enantioselective Preparation of (S)-Metolachlor from Commercially Available (R)-Propylene Oxide
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An enantioselective preparation of (S)-metolachlor has been accomplished. The synthetic route featured the asymmetric preparation of chiral intermediates and the final (S)-metolachlor from commercially available (R)-propylene oxide and a key Fukuyama's process. The key steps, control points, separation purifications, and the whole process are optimized, and the target compound has been successfully prepared in five steps in 51-55% overall yield with excellent enantioselectivity (99% ee) up to a 30 g scale. By judicious choice of synthetic route and selection of starting materials and intermediates, no column chromatographic methods are needed for the separation and purification of the intermediates and the final products. The same strategy was extended as a general method for a series of pesticides and herbicide analogs of Metalaxyl-M and Dimethenamid-P.
- Yang, Peng,Wang, Xiao,Peng, Lin,Chen, Feng,Tian, Fang,Tang, Chao-Zhe,Wang, Li-Xin
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p. 1682 - 1688
(2017/10/25)
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- Design, synthesis and biological evaluation of GPR55 agonists
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GPR55, a G protein-coupled receptor, is an attractive target to alleviate inflammatory and neuropathic pain and treat osteoporosis and cancer. Identifying a potent and selective ligand will aid to further establish the specific physiological roles and pharmacology of the receptor. Towards this goal, a targeted library of 22 compounds was synthesized in a modular fashion to obtain structure-activity relationship information. The general route consisted of coupling a variety of p-aminophenyl sulfonamides to isothiocyanates to form acylthioureas. For the synthesis of a known naphthyl ethyl alcohol motif, route modification led to a shorter and more efficient process. The 22 analogues were analyzed for their ability to serve as agonists at GPR55 and valuable information for both ends of the molecule was ascertained.
- Fakhouri, Lara,Cook, Christopher D.,Al-Huniti, Mohammed H.,Console-Bram, Linda M.,Hurst, Dow P.,Spano, Michael B.S.,Nasrallah, Daniel J.,Caron, Marc G.,Barak, Larry S.,Reggio, Patricia H.,Abood, Mary E.,Croatt, Mitchell P.
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p. 4355 - 4367
(2017/07/22)
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- Potent and selective N-(4-sulfamoylphenyl)thiourea-based GPR55 agonists
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To date, many known G protein-coupled receptor 55 (GPR55) ligands are those identified among the cannabinoids. In order to further study the function of GPR55, new potent and selective ligands are needed. In this study, we utilized the screening results from PubChem bioassay AID 1961 which reports the results of Image-based HTS for Selective Agonists of GPR55. Three compounds, CID1792579, CID1252842 and CID1011163, were further evaluated and used as a starting point to create a series of nanomolar potency GPR55 agonists with N-(4-sulfamoylphenyl)thiourea scaffold. The GPR55 activity of the compounds were screened by using a commercial β-arrestin PathHunter assay and the potential compounds were further evaluated by using a recombinant HEK cell line exhibiting GPR55-mediated effects on calcium signalling. The designed compounds were not active when tested against various endocannabinoid targets (CB1R, CB2R, FAAH, MGL, ABHD6 and ABHD12), indicating compounds' selectivity for the GPR55. Finally, structure-activity relationships of these compounds were explored.
- Yrj?l?, Sari,Parkkari, Teija,Navia-Paldanius, Dina,Laitinen, Tuomo,Kaczor, Agnieszka A.,Kokkola, Tarja,Adusei-Mensah, Frank,Savinainen, Juha R.,Laitinen, Jarmo T.,Poso, Antti,Alexander, Amy,Penman, June,Stott, Lisa,Anskat, Marie,Irving, Andrew J.,Nevalainen, Tapio J.
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p. 119 - 132
(2015/11/24)
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- Triflic acid–catalyzed rearrangement of unalkylated benzene sulfonanilides
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ABSTRACT: Previous work has demonstrated that alkylated benzene sulfonanilides undergo sulfuric acid (98%)–catalyzed rearrangement to alkylamino diaryl sulfones. Similar treatment of their unalkylated analogs typically leads only to hydrolysis. Surprisingly, when the unalkylated benzene sulfonanilides react with triflic acid, rearrangement to sulfones does occur.
- Newcomer, Rebecca,McKee, James,Zanger, Murray
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supporting information
p. 949 - 955
(2016/07/12)
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- Metal Free Bi(hetero)aryl Synthesis: A Benzyne Truce-Smiles Rearrangement
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A new benzyne transformation is described that affords versatile biaryl structures without recourse to transition-metal catalysis or stoichiometric amounts of organometallic building blocks. Aryl sulfonamides add to benzyne upon fluoride activation, and then undergo an aryl Truce-Smiles rearrangement to afford biaryls with sulfur dioxide extrusion. The reaction proceeds under simple reaction conditions and has excellent scope for the synthesis of sterically hindered atropisomeric biaryl amines. All smiles: Metal-free biaryl synthesis is achieved by adding benzyne to arylsulfonamides. A Smiles rearrangement enables C-C bond formation, thus accessing a variety of functionalized biaryls under mild reaction conditions.
- Holden, Catherine M.,Sohel, Shariar M. A.,Greaney, Michael F.
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supporting information
p. 2450 - 2453
(2016/02/18)
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- Highly ortho-Selective Chlorination of Anilines Using a Secondary Ammonium Salt Organocatalyst
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An organocatalytic, highly facile, efficient, and regioselective ortho-chlorination of anilines is described. A secondary ammonium chloride salt has been employed as the catalyst and the reaction can be conducted at room temperature without protection from air and moisture. In addition, the reaction is readily scalable and the catalyst can be recycled and reused. This catalytic protocol has been applied to the efficient synthesis of a highly potent c-Met kinase inhibitor. Mechanistic studies revealed that unique structural features of the secondary ammonium chloride salt are important for both the catalysis and regioselectivity of the electrophilic ortho-chlorination.
- Xiong, Xiaodong,Yeung, Ying-Yeung
-
supporting information
p. 16101 - 16105
(2016/12/26)
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- NH4I-Catalyzed Synthesis of Sulfonamides from Arylsufonylhydrazides and Amines
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A novel and efficient approach to sulfonamides has been developed. Using TBHP as the oxidant and NH4I (20 mol%) as the catalyst, arylsulfonyl hydrazides reacted with amines to provide sulfonamides in moderate to good yields. Possible reaction pathway for the formation of the products was also discussed in this paper. Sulfonimides were synthesized through the oxidation coupling of arylsufonylhydrazides and amines by TBHP/NH4I system in moderate to good yields.
- Yu, Hui,Zhang, Yonghao
-
supporting information
p. 359 - 362
(2016/04/26)
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- A highly efficient heterogeneous copper-catalyzed Chan-Lam coupling reaction of sulfonyl azides with arylboronic acids leading to: N -arylsulfonamides
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A heterogeneous Chan-Lam coupling reaction between sulfonyl azides and arylboronic acids was achieved in MeOH at room temperature in the presence of 10 mol% of an l-proline-functionalized MCM-41-immobilized copper(i) complex [MCM-41-l-proline-CuCl] under air, yielding a variety of N-arylsulfonamides in excellent yields. The new heterogeneous copper complex can be prepared from commercially readily available and inexpensive reagents, and recovered by simple filtration of the reaction solution and recycled at least 8 times without any decreases in activity.
- You, Chongren,Yao, Fang,Yan, Tao,Cai, Mingzhong
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p. 43605 - 43612
(2016/05/24)
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- Palladium-Catalyzed Enantioselective 1,1-Fluoroarylation of Aminoalkenes
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The development of an enantioselective palladium-catalyzed 1,1-fluoroarylation of unactivated aminoalkenes is described. The reaction uses arylboronic acids as the arene source and Selectfluor as the fluorine source to generate benzylic fluorides in good yields with excellent enantioselectivities. This transformation, likely proceeding through an oxidative Heck mechanism, affords 1,1-difunctionalized alkene products.
- He, Ying,Yang, Zhenyu,Thornbury, Richard T.,Toste, F. Dean
-
supporting information
p. 12207 - 12210
(2015/10/12)
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- Sulfonamide formation from sodium sulfinates and amines or ammonia under metal-free conditions at ambient temperature
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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
- Yang, Kai,Ke, Miaolin,Lin, Yuanguang,Song, Qiuling
-
supporting information
p. 1395 - 1399
(2015/03/18)
-
- Flow synthesis and biological activity of aryl sulfonamides as selective carbonic anhydrase IX and XII inhibitors
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A series of secondary and tertiary aryl sulfonamides were synthesized under flow conditions and evaluated for their ability to selectively inhibit tumor-associated carbonic anhydrase isoforms IX and XII. The tested compounds revealed to be highly potent CA IX inhibitors in nanomolar range, and to inhibit CA XII activity with different ranks of potencies. Remarkably, 4-methyl-N-phenyl-benzenesulfonamide was a selective nanomolar CA IX inhibitor with an IC50 of 90 nM.
- Rosatelli, Emiliano,Carotti, Andrea,Ceruso, Mariangela,Supuran, Claudiu T.,Gioiello, Antimo
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supporting information
p. 3422 - 3425
(2014/07/22)
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- Palladium-catalyzed intramolecular oxidative coupling involving double C(sp2)-H bonds for the synthesis of annulated biaryl sultams
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The palladium-catalyzed intramolecular oxidative coupling described herein involves a double C(sp2)-H bond functionalization in sulfonanilides, providing a workable access to biaryl sultams annulated into a six-membered ring that are otherwise difficult to obtain by literature methods. The other synthetic applications of this protocol including the synthesis of biaryl sultams containing a seven-membered ring and analogous sultones are also presented.
- Laha, Joydev K.,Jethava, Krupal P.,Dayal, Neetu
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p. 8010 - 8019
(2015/03/18)
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- Synthesis and structure-activity relationship studies of 4-((2-hydroxy-3-methoxybenzyl)amino)benzenesulfonamide derivatives as potent and selective inhibitors of 12-lipoxygenase
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Human lipoxygenases (LOXs) are a family of iron-containing enzymes which catalyze the oxidation of polyunsaturated fatty acids to provide the corresponding bioactive hydroxyeicosatetraenoic acid (HETE) metabolites. These eicosanoid signaling molecules are involved in a number of physiologic responses such as platelet aggregation, inflammation, and cell proliferation. Our group has taken a particular interest in platelet-type 12-(S)-LOX (12-LOX) because of its demonstrated role in skin diseases, diabetes, platelet hemostasis, thrombosis, and cancer. Herein, we report the identification and medicinal chemistry optimization of a 4-((2-hydroxy-3-methoxybenzyl)amino) benzenesulfonamide-based scaffold. Top compounds, exemplified by 35 and 36, display nM potency against 12-LOX, excellent selectivity over related lipoxygenases and cyclooxygenases, and possess favorable ADME properties. In addition, both compounds inhibit PAR-4 induced aggregation and calcium mobilization in human platelets and reduce 12-HETE in β-cells.
- Luci, Diane K.,Jameson, J. Brian,Yasgar, Adam,Diaz, Giovanni,Joshi, Netra,Kantz, Auric,Markham, Kate,Perry, Steve,Kuhn, Norine,Yeung, Jennifer,Kerns, Edward H.,Schultz, Lena,Holinstat, Michael,Nadler, Jerry L.,Taylor-Fishwick, David A.,Jadhav, Ajit,Simeonov, Anton,Holman, Theodore R.,Maloney, David J.
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p. 495 - 506
(2014/02/14)
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- Copper-catalyzed Chan-Lam Coupling between Sulfonyl Azides and Boronic acids at room temperature
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A mild and efficient method for the synthesis of N-arylsulfonamides in the presence of 10 mol % of CuCl is demonstrated. The reaction proceeds readily at room temperature in an open flask using a variety of sulfonyl azides and boronic acids without any base, ligand, or additive.
- Moon, Soo-Yeon,Nam, Jungsoo,Rathwell, Kris,Kim, Won-Suk
-
supporting information
p. 338 - 341
(2014/04/03)
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- Copper-catalyzed oxidative amination and allylic amination of alkenes
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Enamines and enamides are useful synthetic intermediates and common components of bioactive compounds. A new protocol for their direct synthesis by a net alkene C-H amination and allylic amination by using catalytic Cu II in the presence of MnO2 is reported. Reactions between N-aryl sulfonamides and vinyl arenes furnish enamides, allylic amines, indoles, benzothiazine dioxides, and dibenzazepines directly and efficiently. Control experiments further showed that MnO2 alone can promote the reaction in the absence of a copper salt, albeit with lower efficiency. Mechanistic probes support the involvement of nitrogen-radical intermediates. This method is ideal for the synthesis of enamides from 1,1-disubstituted vinyl arenes, which are uncommon substrates in existing oxidative amination protocols. A new protocol for the direct synthesis of enamides and allylic amines by oxidative N-H/C-H coupling of N-sulfonylanilines with vinylarenes is presented. The reaction works in both inter- and intramolecular modes and is catalyzed by copper salts by using MnO2 as the stoichiometric oxidant (see scheme). Nitrogen heterocycles including indoles, benzothiazine dioxides, and dibenzazepines can be formed. Copyright
- Liwosz, Timothy W.,Chemler, Sherry R.
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supporting information
p. 12771 - 12777
(2013/10/01)
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- Chemoselective nitration of aromatic sulfonamides with tert-butyl nitrite
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A methodology for the efficient conversion of aromatic sulfonamides into their mono-nitro derivatives using tert-butyl nitrite is reported. The reaction exhibits a high degree of chemoselectivity for sulfonamide functionalized aryl systems, even in the presence of other sensitive or potentially reactive functionalities.
- Kilpatrick, Brenden,Heller, Markus,Arns, Steve
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supporting information
p. 514 - 516
(2013/02/25)
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- Gas-phase fragmentations of anions derived from N-phenyl benzenesulfonamides
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In addition to the well-known SO2 loss, there are several additional fragmentation pathways that gas-phase anions derived from N-phenyl benzenesulfonamides and its derivatives undergo upon collisional activation. For example, N-phenyl benzenesulfonamide fragments to form an anilide anion (m/z 92) by a mechanism in which a hydrogen atom from the ortho position of the benzenesulfonamide moiety is specifically transferred to the charge center. Moreover, after the initial SO2 elimination, the product ion formed undergoes primarily, an inter-annular H2 loss to form a carbazolide anion (m/z 166) because the competing intra-annular H2 loss is significantly less energetically favorable. Results from tandem mass spectrometric experiments conducted with deuterium-labeled compounds confirmed that the inter-ring mechanism is the preferred pathway. Furthermore, N-phenyl benzenesulfonamide and its derivatives also undergo a phenyl radical loss to form a radical ion with a mass-to-charge ratio of 155, which is in violation of the so-called "even-electron rule." [Figure not available: see fulltext.]
- Hibbs, John A.,Jariwala, Freneil B.,Weisbecker, Carl S.,Attygalle, Athula B.
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p. 1280 - 1287
(2013/08/23)
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- Sulfonamide synthesis via oxyma-O-sulfonates - Compatibility to acid sensitive groups and solid-phase peptide synthesis
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A milder and more efficient procedure for the synthesis of sulfonamides by activating sulfonic acid groups as the corresponding sulfonate esters of ethyl 2-cyano-2-(hydroxyimino)acetate (Oxyma) is reported. This method is greener than all other existing protocols for the purpose. Other important advantages lie in (a) its applicability to less nucleophilic anilines under ambient and milder conditions and (b) its compatibility with solid phase peptide synthesis and acid-labile groups such as trityl (Trt) and tBu, which empowers the solid phase synthesis of sulfonamides of various peptides. To illustrate this, the syntheses of three sulfonamide derivatives of the peptide GAILG-NH2, which is relevant in the context of drug design against type 2 diabetes, are demonstrated by using Fmoc-based solid-phase peptide synthesis (SPPS). The activation of sulfonic acids as their corresponding O-sulfonate esters facilitates sulfonamide synthesis, which can be applied to those substrates that possess acid-labile functional groups and is compatible with solid phase synthesis. Copyright
- Palakurthy, Nani Babu,Dev, Dharm,Rana, Shubhasmin,Nadimpally, Krishna Chaitanya,Mandal, Bhubaneswar
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p. 2627 - 2633
(2013/06/04)
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- 4-Amino-5-(arylaminomethyl)-2-(methylthio)furo[2,3-d]pyrimidines via Mitsunobu reaction of 4-amino-5-(hydroxymethyl)-2-(methylthio)furo[2,3-d] pyrimidine with N-mesyl- and N-nosylarylamines
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An efficient method for the synthesis of 4-amino-5-(arylaminomethyl)-2- (methylthio)furo[2,3-d]pyrimidines via the Mitsunobu reaction of 4-amino-5-(hydroxymethyl)-2-(methylthio)furo[2,3-d]pyrimidine with N-mesyl- and N-nosylarylamines, and subsequent removal of the mesyl and nosyl groups, has been developed. The influence of substituents in the arylamine moiety on the Mitsunobu reaction was investigated. An unexpected nucleophilic substitution of a nitro group in the reaction of N-({4-amino-2-(methylsulfonyl)furo[2,3-d] pyrimidin-5-yl}methyl)-4-nitro-N-phenylbenzenesulfonamide with sodium methoxide was observed. Georg Thieme Verlag Stuttgart · New York.
- Masevicius, Viktoras,Petraityte, Grazina,Tumkevicius, Sigitas
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experimental part
p. 1329 - 1338
(2012/07/01)
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- ZnO and ZnO-nanoparticles: Efficient and reusable heterogeneous catalysts for one-pot synthesis of N-acylsulfonamides and sulfonate esters
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Commercially available and preparative ZnO nanoparticles are reported as efficient and reusable catalysts for the chemoselective synthesis of N-acylsulfonamides and sulfonate esters. A one-pot sequential sulfonylation and acylation of amines took place to afford the N-acylsulfonamides in excellent yields under solvent-free conditions. The ZnO catalyst can be reused for without significant loss of catalytic activity.
- Tamaddon, Fatemeh,Sabeti, Mohammad Reza,Jafari, Abbas Ali,Tirgir, Farhang,Keshavarz, Elham
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experimental part
p. 41 - 45
(2012/01/12)
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- A green, catalyst-free method for the synthesis of sulfonamides and sulfonylazides
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A novel, green method for the efficient synthesis of sulfonamide and sulfonylazide derivatives by the reaction of sulfonyl chlorides with amines or sodium azide under catalyst-free conditions has been developed. The reactions proceed with high yields and excellent selectivities in short reaction times. Copyright Taylor & Francis Group, LLC.
- Jafarpour, Maasoumeh,Rezaeifard, Abdolreza,Golshani, Tayebeh
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experimental part
p. 140 - 148
(2011/04/22)
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- Synthesis and biological evaluation of naphthoquinone analogs as a novel class of proteasome inhibitors
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Screening of the NCI Diversity Set-1 identified PI-083 (NSC-45382) a proteasome inhibitor selective for cancer over normal cells. Focused libraries of novel compounds based on PI-083 chloronaphthoquinone and sulfonamide moieties were synthesized to gain a better understanding of the structure-activity relationship responsible for chymotrypsin-like proteasome inhibitory activity. This led to the demonstration that the chloronaphthoquinone and the sulfonamide moieties are critical for inhibitory activity. The pyridyl group in PI-083 can be replaced with other heterocyclic groups without significant loss of activity. Molecular modeling studies were also performed to explore the detailed interactions of PI-083 and its derivatives with the β5 and β6 subunits of the 20S proteasome. The refined model showed an H-bond interaction between the Asp-114 and the sulfonamide moiety of the PI-083 in the β6 subunit.
- Lawrence, Harshani R.,Kazi, Aslamuzzaman,Luo, Yunting,Kendig, Robert,Ge, Yiyu,Jain, Sanjula,Daniel, Kenyon,Santiago, Daniel,Guida, Wayne C.,Sebti, Said M.
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experimental part
p. 5576 - 5592
(2010/09/15)
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- Synthesis and SAR of novel, 4-(phenylsulfamoyl)phenylacetamide mGlu 4 positive allosteric modulators (PAMs) identified by functional high-throughput screening (HTS)
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Herein we disclose the synthesis and SAR of a series of 4-(phenylsulfamoyl)phenylacetamide compounds as mGlu4 positive allosteric modulators (PAMs) that were identified via a functional HTS. An iterative parallel approach to these compounds culminated in the discovery of VU0364439 (11) which represents the most potent (19.8 nM) mGlu4 PAM reported to date.
- Engers, Darren W.,Gentry, Patrick R.,Williams, Richard,Bolinger, Julie D.,Weaver, C. David,Menon, Usha N.,Conn, P. Jeffrey,Lindsley, Craig W.,Niswender, Colleen M.,Hopkins, Corey R.
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scheme or table
p. 5175 - 5178
(2010/10/02)
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- Analgesic agents without gastric damage: Design and synthesis of structurally simple benzenesulfonanilide-type cyclooxygenase-1-selective inhibitors
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In order to create novel analgesic agents without gastric disturbance, structurally simple cyclooxygenase-1 (COX-1) inhibitors with a benzenesulfonanilide skeleton were designed and synthesized. As a result, compounds 11f and 15a, which possess a p-amino group on the benzenesulfonyl moiety and p-chloro group on the anilino moiety, showed COX-1-selective inhibition. Moreover compound 11f, which is the most potent compound in this study showed more potent analgesic activity than that of aspirin at 30 mg/kg by po. The anti-inflammatory activity and gastric damage, however, were very weak or not detectably different from aspirin. Since the structure of our COX-1 inhibitors are very simple, they may be useful as lead compounds for superior COX-1 inhibitors as analgesic agents without gastric disturbance.
- Zheng, Xiaoxia,Oda, Hiroyuki,Takamatsu, Kayo,Sugimoto, Yukio,Tai, Akihiro,Akaho, Eiichi,Ali, Hamed Ismail,Oshiki, Toshiyuki,Kakuta, Hiroki,Sasaki, Kenji
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p. 1014 - 1021
(2007/10/03)
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- Highly specific N-monomethylation of primary aromatic amines
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A synthetic methodology for the specific conversion of primary aromatic amines into their N-monomethyl derivatives under very mild conditions is presented. Anilines are treated with 4-nitrobenzenesulfonyl (nosyl) chloride to generate the corresponding sulfonamides 2 in high yields. The subsequent N-methylation reaction of the sulfonamides 2 with a solution of diazomethane is rapid and quantitative. Removal of the nosyl protecting group is readily carried out using the reagent system mercaptoacetic acid/1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) affording the N-monomethylated aromatic amines 4. The procedure is convenient, efficient, and gives rise to the N-monomethyl-anilines exclusively.
- Le Pera, Adolfo,Leggio, Antonella,Liguori, Angelo
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p. 6100 - 6106
(2007/10/03)
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- Spontaneous resolution of aromatic sulfonamides: Effective screening method and discrimination of absolute structure
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(Chemical Equation Presented) An effective screening method combining parallel synthesis and solid-state CD measurements was established to identify achiral aromatic sulfonamides that show spontaneous resolution with rapidity. We found that 4 of the 12 achiral sulfonamides crystallized as chiral crystals through this method. The chirality of each sulfonamide was discriminated by solid-state CD spectra and Flack parameter in an X-ray analysis. Correspondence between the observed Cotton effect and the absolute configuration could be confirmed by time-dependent DFT calculations.
- Kato, Takako,Okamoto, Iwao,Tanatani, Aya,Hatano, Terutaka,Uchiyama, Masanobu,Kagechika, Hiroyuki,Masu, Hyuma,Katagiri, Kosuke,Tominaga, Masahide,Yamaguchi, Kentaro,Azumaya, Isao
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p. 5017 - 5020
(2007/10/03)
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- Novel lead structures for antimalarial farnesyltransferase inhibitors
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Through the combination of nitrophenylfurylacryloyl moiety which has been designed to occupy an aryl binding site of farnesyltransferase with several AA(X)-peptidomimetic substructures some novel farnesyltransferase inhibitors were obtained. Evaluation of their antimalarial activity and some initial modifications yielded a 4-benzophenone- and a sulfonamid-based novel lead for antimalarial farnesyltransferase inhibitors.
- Kettler,Sakowski,Wiesner,Ortmann,Jomaa,Schlitzer, Martin
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p. 323 - 327
(2007/10/03)
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- Novel arylsulfoanilide-oxindole hybrid as an anticancer agent that inhibits translation initiation
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Structure-activity relationship studies of substituted arylsulfoanilides as antiproliferatives, which are mediated by the partial depletion of intracellular Ca2+ stores, resulted in the identification of compounds with micromolar activity against lung cancer cells in a growth inhibition assay. Incorporating the substitution pattern of the best arylsulfoanilides onto the 3-phenyloxindole scaffold resulted in a potent arylsulfoanilide-oxindole hybrid, 27. Compound 27 inhibits cancer cell growth by partial depletion of intracellular Ca2+ stores and phosphorylation of eIF2α.
- Natarajan, Amarnath,Guo, Yuhong,Harbinski, Frederick,Fan, Yun-Hua,Chen, Han,Luus, Lia,Diercks, Jana,Aktas, Huseyin,Chorev, Michael,Halperin, Jose A.
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p. 4979 - 4982
(2007/10/03)
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- Effect of para substitution on dissociation of N-phenylbenzenesulfonamides
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The reaction of substituted anilines and benzenesulfonyl chlorides has been used to prepare 49 substituted N-phenylbenzenesulfonamides of general formula 4-X-C6H4SO2NHC6H4-Y- 4′. Their purity was checked by elemental analysis. The substituents X and Y include H, CH3, CH3O, Cl, Br, CN, and NO2. The dissociation constants of all compounds were determined by potentiometric titration in methanol, acetonitrile, N,N-dimethylformamide, and pyridine. The obtained dissociation constants, pKHA, were correlated with various sets of substituent constants. It was found that the effects of substituents X and Y on the dissociation are best described by using the Hammett equation with σp constants and the Yukawa-Tsuno equation with σp- and σp constants, respectively. This result confirms the direct conjugation of Y substituent with the reaction centre. The explained variability using the additive model was above 96% in all the solvents used. The data also provided information about the transmission effect of the SO2 group. The average dissociation constants were further processed by the latent variables methods, principal components and conjugated deviations analyses.
- Mansfeld, Martin,Parik, Patrik,Ludwig, Miroslav
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p. 1479 - 1490
(2007/10/03)
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- Antifungal activities of N-arylbenzenesulfonamides against phytopathogens and control efficacy on wheat leaf rust and cabbage club root diseases.
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A set of N-arylbenzenesulfonamides with various substituents at the arylamine and benzenesulfonyl positions were prepared, and their antifungal properties were measured in vitro against such plant pathogenic fungi as Pythium ultimum, Phytophthora capsici, Rhizoctonia solani, and Botrytis cinerea. Compounds 3, 4, 8, 9, 10, 14, 16, 18, 20, 21, 24 and 27 had antifungal activity over a broad spectrum of the phytopathogenic fungi tested, where 50% of inhibition (ED50) was in the range of 3-15 microg/ml. Based on the in vitro activity, six derivatives (3, 4, 10, 18, 21 and 27) were selected and tested further for their fungicidal efficacy in vivo. The fungicidal efficacy of 10, 21 and 27 had a disease control value of over 85% at 50 microg/ml against wheat leaf rust, while that of 4 was selective against cabbage club root disease.
- Kang, Jae Gon,Hur, Jong Hyun,Choi, Sung Jun,Choi, Gyung Ja,Cho, Kwang Yun,Ten, Leonid N,Park, Ki Hun,Kang, Kyu Young
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p. 2677 - 2682
(2007/10/03)
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- Bimolecular nucleophilic displacement at tertiary carbon centers: Aminolyses of 2-cyano-2-propyl and 1-cyanocyclooctyl arenesulfonates
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Kinetic studies were carried out on the reactions of anilines with 2-cyano-2-propyl and 1-cyanocyclooctyl arenesulfonates in acetonitrile at 50·0°C. The second-order rate constants for the former are in general greater than those for the latter but the rates of the two become comparable for a strong nucleofuge. The cross-interaction constants, ρXZ (and βXZ), are considerably smaller (ca -0·04) than those for the primary (ca 0·33) and secondary (ca 0·12) compounds. The negative sign and small magnitude are consistent with a dissociative SN2 mechanism with a loose transition state structure. The ab initio MO theoretical results for Cl- + RCl?ClR + Cl- at the MP2 level (MP2/6-31 + G*//MP2/6-31 + G*) confirm the looseness of the transition state for the tertiary (R) alkyl compounds. The average r*(Cl...Cl) value is 4·88 ± 0·03 A, which is larger than those for the reactions at primary (4·68± 0·02 A) and secondary (4·80 ± 0·02 A) carbon centers. Thus a looser transition state with a smaller magnitude of ρXZ for the tertiary carbon centers has a larger theoretical r*(Cl-Cl) value.
- Oh, Hyuck Keun,Kwon, Young Bong,Chung, Dong Soo,Lee, Ikchoon
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p. 683 - 688
(2007/10/03)
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