- COMPOUNDS
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The invention relates to novel compounds for use as inhibitors of NLRP3 inflammasone production, wherein such compounds are as defined by compounds of formula (I) and wherein the integers R1, R2 and R3 are defined in the description, and where the compounds may be useful as medicaments, for instance for use in the treatment of a disease or disorder that is associated with NLRP3 inflammasome activity.
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Page/Page column 52; 87-88
(2021/12/08)
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- Electroselective and Controlled Reduction of Cyclic Imides to Hydroxylactams and Lactams
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An efficient and practical electrochemical method for selective reduction of cyclic imides has been developed using a simple undivided cell with carbon electrodes at room temperature. The reaction provides a useful strategy for the rapid synthesis of hydroxylactams and lactams in a controllable manner, which is tuned by electric current and reaction time, and exhibits broad substrate scope and high functional group tolerance even to reduction-sensitive moieties. Initial mechanistic studies suggest that the approach heavily relies on the utilization of amines (e.g., i-Pr2NH), which are able to generate α-aminoalkyl radicals. This protocol provides an efficient route for the cleavage of C-O bonds under mild conditions with high chemoselectivity.
- Bai, Ya,Shi, Lingling,Zheng, Lianyou,Ning, Shulin,Che, Xin,Zhang, Zhuoqi,Xiang, Jinbao
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supporting information
p. 2298 - 2302
(2021/04/05)
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- Organocatalyzed Synthesis of Highly Functionalized Phthalimides via Diels-Alder Reaction Employing Two Dienophiles
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An efficient and facile protocol for the synthesis of biologically and pharmaceutically important phthalimides is developed by l-proline-catalyzed reaction between two dienophiles of α,β-unsaturated aldehydes and maleimides. The reaction involves an efficient benzannulation that proceeds via a formal [4 + 2] cycloaddition of azadiene intermediates generated in situ from enals and N-substituted maleimides. This protocol provides a variety of functionalized phthalimide derivatives, including a potent COX-2 enzyme inhibitor.
- Akhtar, Muhammad Saeed,Lee, Yong Rok
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p. 15129 - 15138
(2020/12/02)
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- Synthesis of imides via palladium-catalyzed three-component coupling of aryl halides, isocyanides and carboxylic acids
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A palladium-catalyzed three-component synthesis of acyclic imides from feedstock aryl halides, carboxylic acids and isocyanides through the intermediacy of isoimides has been developed. The key to the success of this approach was controlled isocyanide slow addition and organic/aqueous biphasic conditions. This transition-metal-catalyzed approach features readily available starting materials, atom- and step-economy, good functional group compatibility and gram-scale synthetic capability. Utilization of this new method is illustrated in the late-stage functionalization of drugs Carprofen, Loxoprofen and Flurbiprofen. This strategy has also been successfully applied in the synthesis of cyclic imides including phthalimide, homophthalimide, and 2H-2-benzazepine-1,3-dione derivatives.
- Wang, Bo,He, Dan,Ren, Beige,Yao, Tuanli
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supporting information
p. 900 - 903
(2020/02/03)
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- Ru-Catalyzed Selective C-H Bond Hydroxylation of Cyclic Imides
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We report on cyclic imides as weak directing groups for selective monohydroxylation reactions using ruthenium catalysis. Whereas acyclic amides are known to promote the hydroxylation of the C(sp2)-H bond enabling five-membered ring ruthenacycle intermediates, the cyclic imides studied herein enabled the hydroxylation of the C(sp2)-H bond via larger six-membered ruthenacycle intermediates. Furthermore, monohydroxylated products were exclusively obtained (even in the presence of overstoichiometric amounts of reagents), which was rationalized by the difficulty to accommodate coplanar intermediates once the first hydroxyl group was introduced into the substrate. The same reactivity was observed in the presence of palladium catalysts.
- Yuan, Yu-Chao,Bruneau, Christian,Dorcet, Vincent,Roisnel, Thierry,Gramage-Doria, Rafael
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p. 1898 - 1907
(2019/02/05)
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- Unmasking Amides: Ruthenium-Catalyzed Protodecarbonylation of N-Substituted Phthalimide Derivatives
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The unprecedented transformation of a wide range of synthetically appealing phthalimides into amides in a single-step operation has been achieved in high yields and short reaction times using a ruthenium catalyst. Mechanistic studies revealed a unique, homogeneous pathway involving five-membered ring opening and CO2 release with water being the source of protons.
- Yuan, Yu-Chao,Kamaraj, Raghu,Bruneau, Christian,Labasque, Thierry,Roisnel, Thierry,Gramage-Doria, Rafael
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supporting information
p. 6404 - 6407
(2017/12/08)
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- Palladium-Catalyzed Synthesis of 1H-Indenes and Phthalimides via Isocyanide Insertion
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A new and versatile multicomponent domino strategy has been developed for the synthesis of a series of 1H-indene and phthalimide derivatives from simple and readily available starting materials. This process operating under mild conditions shows a broad substrate scope with moderate to excellent yields.
- Wang, Xu,Xiong, Wenfang,Huang, Yubing,Zhu, Jiayi,Hu, Qiong,Wu, Wanqing,Jiang, Huanfeng
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p. 5818 - 5821
(2017/11/10)
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- Synthetic method for N-substituted imide
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The invention provides a synthetic method for N-substituted imide. According to the method, aromatic ketone and amine are used as substrates, air or oxygen is used as an oxygen source, and cyclic imide is produced under liquid phase conditions under the action of a catalyst. The method is mild in conditions, high in oxidation efficiency and high in product yield; and since the method uses air or oxygen as the oxygen source, the method is economic and environment-friendly and has good application prospect.
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Paragraph 0016; 0022; 0023; 0024; 0025
(2017/04/20)
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- Synthesis of cyclic imides (methylphtalimides, carboxylic acid phtalimides and itaconimides) and evaluation of their antifungal potential
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Background: This paper describes the synthesis of three different subfamilies of cyclic imides: methylphtalimides, carboxyl acid phtalimides and itaconimides. Methods: Fifteen compounds (five of each sub-family) were obtained by the reaction of appropriat
- Stiz, Dorimar,Corrêa, Rogério,D'Auria, Felicia D.,Simonetti, Giovanna,Cechinel-Filho, Valdir
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p. 647 - 654
(2016/10/18)
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- Visible-light induced isoindoles formation to trigger intermolecular diels-alder reactions in the presence of air
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Visible-light induced isoindole formation triggered an intermolecular Diels-Alder reaction with dienophiles such as acetylenedicarboxylate and maleimides in the presence of air. The reaction resulted in excellent diastereoselctivity and high yields under
- Lin, Chao,Zhen, Le,Cheng, Yong,Du, Hong-Jin,Zhao, Hui,Wen, Xiaoan,Kong, Ling-Yi,Xu, Qing-Long,Sun, Hongbin
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supporting information
p. 2684 - 2687
(2015/06/16)
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- Cuprous Oxide Catalyzed Oxidative C-C Bond Cleavage for C-N Bond Formation: Synthesis of Cyclic Imides from Ketones and Amines
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Selective oxidative cleavage of a C-C bond offers a straightforward method to functionalize organic skeletons. Reported herein is the oxidative C-C bond cleavage of ketone for C-N bond formation over a cuprous oxide catalyst with molecular oxygen as the oxidant. A wide range of ketones and amines are converted into cyclic imides with moderate to excellent yields. In-depth studies show that both α-C-H and β-C-H bonds adjacent to the carbonyl groups are indispensable for the C-C bond cleavage. DFT calculations indicate the reaction is initiated with the oxidation of the α-C-H bond. Amines lower the activation energy of the C-C bond cleavage, and thus promote the reaction. New insight into the C-C bond cleavage mechanism is presented.
- Wang, Min,Lu, Jianmin,Ma, Jiping,Zhang, Zhe,Wang, Feng
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supporting information
p. 14061 - 14065
(2016/01/25)
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- Ruthenium(II)-catalyzed N-substituted phthalimide synthesis via C-H activation/[3+2] annulation
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Ruthenium-catalyzed intermolecular [3 + 2] annulation pathway for aromatic acids with isocyanates to afford N-substituted phthalimide in one step is demonstrated, which provides an efficient process to direct preparation of phthalimide from commercially a
- Dong, Xue-Fen,Fan, Juan,Shi, Xian-Ying,Liu, Ke-Yan,Wang, Peng-Min,Wei, Jun-Fa
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- Ruthenium(II)-Catalyzed C-H Activation with Isocyanates: A Versatile Route to Phthalimides
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A cationic ruthenium(II)-complex was utilized in the efficient synthesis of phthalimide derivatives by C- H activation with synthetically useful amides. The reaction proceeded through a mechanistically unique insertion of a cycloruthenated species into a C- Het multiple bond of isocyanate. The novel method also proved applicable for the synthesis of heteroaromatic unsymmetric diamides as well as a potent COX-2 enzyme inhibitor. A convenient route to phthalimide: A convergent method for the ruthenium(II)-catalyzed imidation of easily accessible benzamides by C- H functionalization was developed (see scheme). The methodology was successfully applied to the preparation of synthetically challenging unsymmetrical heteroaromatic diamides and proved amenable to a step-economic synthesis of a potent COX-2 enzyme inhibitor.
- Desarkar, Suman,Ackermann, Lutz
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supporting information
p. 13932 - 13936
(2016/02/18)
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- A rhodium-catalyzed cascade cyclization: Direct synthesis of N-substituted phthalimides from isocyanates and benzoic acids
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A rhodium(III)-catalyzed amidation between benzoic acids and isocyanates via direct functionalization of an ortho C-H bond followed by intramolecular cyclization is described. This cascade cyclization affords N-substituted phthalimides in one step in 26-91% yields. The reaction is highly atom-economical, since no theoretical waste except for water is generated in the reaction.
- Shi, Xian-Ying,Renzetti, Andrea,Kundu, Soumen,Li, Chao-Jun
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supporting information
p. 723 - 728
(2014/04/03)
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- Synthesis, anti-inflammatory activity and COX-1/COX-2 inhibition of novel substituted cyclic imides. Part 1: Molecular docking study
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A group of cyclic imides (1-13) was designed for evaluation as selective COX-2 inhibitors and investigated in vivo for their anti-inflammatory activities using carrageenan-induced rat paw edema model. Compounds 5b, 6b, 11b, 11c, 12b and 12c were proved to be potent COX-2 inhibitors with IC50 range of 0.1-1.0 μM. In vitro COX-1/COX-2 inhibition structure-activity studies identified compound 5b as a highly potent (IC50 = 0.1 μM), and an extremely selective [COX-2 (SI) = 400] comparable to celecoxib [COX-2 (SI) > 333.3], COX-2 inhibitor that showed superior anti-inflammatory activity (ED 50 = 104 mg/kg) relative to diclofenac (ED50 = 114 mg/kg). A Virtual screening was carried out through docking the designed compounds into the COX-2 binding site to predict if these compounds have analogous binding mode to the COX-2 inhibitors. Molecular modeling (docking) study showed that the CH3O substituents of 5b inserted deep inside the 2°-pocket of the COX-2 active site, where the O-atoms of such group underwent a H-bonding interaction with His90 (2.43, 2.83 ), Arg513 (2.89 ) and Tyr355 (3.34 ). Docking study of the synthesized compound 5b into the active site of COX-2 revealed a similar binding mode to SC-558, a selective COX-2 inhibitor.
- Abdel-Aziz, Alaa A.-M.,Eltahir, Kamal E.H.,Asiri, Yousif A.
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scheme or table
p. 1648 - 1655
(2011/05/06)
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- Intermolecular oxidative C-N bond formation under metal-free conditions: Control of chemoselectivity between aryl sp2 and benzylic sp 3 C-H bond imidation
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A new synthetic approach toward intermolecular oxidative C-N bond formation of arenes has been developed under transition-metal-free conditions. Complete control of chemoselectivity between aryl sp2 and benzylic sp 3 C-H bond imidation was achieved by the choice of nitrogen sources, representatively being phthalimide and dibenzenesulfonimide, respectively.
- Kim, Hyun Jin,Kim, Jiyu,Cho, Seung Hwan,Chang, Sukbok
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supporting information; experimental part
p. 16382 - 16385
(2011/12/13)
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- Microwave-assisted parallel synthesis of a 2-aryl-1H-isoindole-1,3-dione library
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An efficient parallel synthesis of a representative 28-member library of phthalimides is described. Parallel chromatography afforded the library members in suitable purity and with high yields.
- Barchín, Bernardo M.,Cuadro, Ana M.,Alvarez-Builla, Julio
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p. 343 - 345
(2007/10/03)
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- Synthesis and cycloaddition reactions of 1-(arylthio)-1,3-dienes. A combined experimental and theoretical study of bicyclic adducts structures
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A method giving simple access to various 1-(phenylthio)-4-substituted-1,3-dienes (5-10) is described. The influence of the different functionalizations introduced on the dienic systems has been tested in a set of classical [4 + 2] cycloaddition reactions. Both the endo/exo and regio selectivities have been investigated. While the endo compound is, as expected, the only or major isomer in all cases, the regio competition between sulfur and oxygen is in favor of the oxygen substituent in the case studied here, in contrast to related works. For one type of adduct, X-ray crystallographic analysis and NMR spectroscopy have been used in conjunction with ab initio and semiempirical AM1 calculations to determine the structure and conformations of products as well as the energetic pathway from the primary concave endo cycloadduct (28) to a rearranged bicyclic structure (39). The theoretical results fully support the occurrence of a photochemical [1,3] sigmatropic shift of the thiophenyl group.
- Maddaluno, Jacques,Gaonac'h, Odile,Marcual, Albert,Toupet, Loic,Giessner-Prettre, Claude
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p. 5290 - 5306
(2007/10/03)
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- Preparation of N-Substituted Phthalimides by Palladium-Catalyzed Carbonylation and Coupling of o-Dihalo Aromatics and Primary Amines
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A novel method for the formation of N-substituted phthalimides is described which is based on the palladium-catalyzed carbonylation and coupling of o-dihalo aromatics and primary amines.Optimal conditions established for the reaction using o-diiodobenzene and aniline were DMAc (0.2 M), 115 deg C, 90 psi of CO, 3 percent PdCl2L2, and 2.4 equiv of DBU.This process is tolerant of a wide variety of functional groups and gives good yields of the desired products.Variables such as temperature, catalyst type and loading, CO pressure, solvent, and base were examined to optimize this reaction.The reaction of aniline with 1,2-dibromocyclopentene under similar conditions gave a variety of products.
- Perry, Robert J.,Turner, S. Richard
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p. 6573 - 6579
(2007/10/02)
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