- Visible-Light- And PPh3-Mediated Direct C-N Coupling of Nitroarenes and Boronic Acids at Ambient Temperature
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We present here a metal-free, visible-light- and triphenylphosphine-mediated intermolecular, reductive amination between nitroarenes and boronic acids at ambient temperature without any photocatalyst. Mechanistically, a slow reduction of nitroarenes to a nitroso and, finally, a nitrene intermediate occurs that leads to the amination product with concomitant 1,2-aryl/-alkyl migration from a boronate complex. A wide range of nitroarenes underwent C-N coupling with aryl-/alkylboronic acids providing high yields.
- Manna, Kartic,Ganguly, Tanusree,Baitalik, Sujoy,Jana, Ranjan
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p. 8634 - 8639
(2021/11/01)
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- Melatonin derivatives combat with inflammation-related cancer by targeting the Main Culprit STAT3
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The combination between two well-studied bioactive compounds melatonin and salicylic acid with proper modifications unexpectedly creates a sharp pair of “scissors” cutting off the vicious connection between inflammation and cancer by targeting a key contributor Signal Transducers and Activators of Transcription 3 (STAT3) in the two pathological processes. A representative compound P-3 with IC50 values on each tested cell line ranging from 7.37 to 18.62 μM among the designed melatonin derivatives is equipped with the ability of curbing inflammation-promoting cancer by down-regulating the expression, activation and nuclear translocation of STAT3, breaking the feedforward loop of STAT3 activation by decreasing the expression of pro-tumorigenic cytokines, and inducing cell apoptosis through ROS triggered Cyto-c/Caspase-3 pathway. This study suggests that the melatonin derivative P-3 is likely to become a promising chemical structure for developing the novel anti-cancer agents taking effect through hindering the mutual-promoting processes between inflammation and cancer.
- Ma, Shumeng,Zhu, Longqing,Fan, Xiaohong,Luo, Tian,Liu, Dan,Liang, Ziyi,Hu, Xiaoling,Shi, Tao,Tan, Wen,Wang, Zhen
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- Method for accelerating synthesis time of methorphan acid
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The invention relates to a method for accelerating synthetic time of mefenamic acid. The method comprises the following steps: performing a reaction by taking o-chlorobenzoic acid, sodium carbonate and 2,3-dimethyl aniline as main raw materials, taking copper powder as a catalyst, and taking N,N-dimethyl formamide and toluene as solvents, performing heating, enabling mixed steam in a reaction kettle to enter a rectifying tower which uses a Dixon ring as a filler, finally performing acidification, performing cooling, and performing filtering to obtain the mefenamic acid crude product. Accordingto the invention, drainage time in the reaction process is accelerated through continuous reflux and evaporation of the rectifying tower, so that the overall synthetic time of the mefenamic acid is accelerated, and the method has the advantages of a high reaction yield, good product quality and high synthetic time, reduces the costs, solves the problem of relatively long synthetic time in a current preparation method, and has good application prospects.
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Paragraph 0021-0028
(2020/05/01)
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- Development of Carbon-Neutral Cellulose-Supported Heterogeneous Palladium Catalysts for Chemoselective Hydrogenation
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Palladium catalysts immobilized on cellulose particles (Pd/CLP) and on a cellulose-monolith (Pd/CLM) were developed. These composites were applied as hydrogenation catalysts and their catalyst activities were evaluated. Although both catalysts catalyzed the deprotection of benzyloxycarbonyl-protected aromatic amines (Ar-N-Cbz) and aromatic benzyl esters (Ar-CO2Bn), only Pd/CLM could accomplish the hydrogenolysis of aliphatic-N-Cbz and aliphatic-CO2Bn protective groups. The difference in the physical structure of the cellulose supports induced unique chemoselectivity. Aliphatic-N-Cbz and aliphatic-CO2Bn groups were tolerated under the Pd/CLP-catalyzed hydrogenation conditions, while Ar-N-Cbz, Ar-CO2Bn, alkene, alkyne, azido and nitro groups could be smoothly reduced.
- Yamada, Tsuyoshi,Teranishi, Wataru,Park, Kwihwan,Jiang, Jing,Tachikawa, Takumu,Furusato, Shinichi,Sajiki, Hironao
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p. 4052 - 4058
(2020/07/13)
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- Design, synthesis and biological evaluation of acridone analogues as novel STING receptor agonists
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STING (Stimulator of Interferon Genes) has become a focal point in immunology research and a target in drug discovery. The discovery of a potent human-STING agonist is expected to revolutionize current anti-virus or cancer immunotherapy. Inspired by the structure and function of murine STING-specific agonists (DMXAA and CMA), we rationally designed and synthesized four series of novel compounds for the enhancement of human sensitivity. In the cell-based assay, we identified six compounds from all the synthetic small molecules: 2g, 9g, and 12b are STING agonists that are efficacious across species, and all have the skeleton of acridone; 1b, 1c, and 12c just function in the murine STING pathway. Notably, 12b exhibits the best activity among the six agonists, and its inductions of both human and murine STING-dependent signalling are similar to that of 2′3′-cGAMP, which is a well-known STING inducer. While a protein assay indicated that 2 g, 9 g, and 12b could activate the pathway by directly binding human STING, 12b also displayed the strongest binding affinity. Additionally, our studies show that 12b can induce faster, more powerful, and more durable responses of assorted cytokines in a native system than 2′3′-cGAMP. Consequently, our team is the first to successfully modify murine STING agonists to obtain human sensitivity, and these results suggest that 12b is a potent direct-human-STING agonist. Additionally, the acridone analogues demonstrate tremendous potential in the treatment of tumours or viral infections.
- Chang, Jia-jia,Hou, Shi,Lan, Xiu-juan,Li, Song,Li, Wei,Sun, Wei,Xiao, Jun-hai,Yan, Xin-lin,Yang, Xiao-hong
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- Redox-neutral decarboxylative photocyclization of anthranilic acids
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A mild metal-, catalyst-, and oxidant-free photoredox neutral system has been found to efficiently enable intramolecular decarboxylative cyclization of anthranilic acids. This facile protocol provides an alternative method for the synthesis of carbazoles. Mechanistic studies reveal a key photoinduced 6π-electrocyclization process and formic acid was released as the sole byproduct.
- Huang, Huawen,Deng, Kun,Deng, Guo-Jun
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supporting information
p. 8243 - 8247
(2020/12/29)
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- Intermolecular Reductive C-N Cross Coupling of Nitroarenes and Boronic Acids by PIII/PV=O Catalysis
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A main group-catalyzed method for the synthesis of aryl- and heteroarylamines by intermolecular C-N coupling is reported. The method employs a small-ring organophosphorus-based catalyst (1,2,2,3,4,4-hexamethylphosphetane) and a terminal hydrosilane reductant (phenylsilane) to drive reductive intermolecular coupling of nitro(hetero)arenes with boronic acids. Applications to the construction of both Csp2-N (from arylboronic acids) and Csp3-N bonds (from alkylboronic acids) are demonstrated; the reaction is stereospecific with respect to Csp3-N bond formation. The method constitutes a new route from readily available building blocks to valuable nitrogen-containing products with complementarity in both scope and chemoselectivity to existing catalytic C-N coupling methods.
- Nykaza, Trevor V.,Cooper, Julian C.,Li, Gen,Mahieu, Nolwenn,Ramirez, Antonio,Luzung, Michael R.,Radosevich, Alexander T.
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p. 15200 - 15205
(2018/11/30)
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- Mefenamic acid and synthesis technology thereof
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The invention discloses a mefenamic acid. The mefenamic acid is prepared by the following steps: taking o-chlorobenzoic acid and 2,3-dimethylaniline as the reactants and weakly alkaline salt as the acid binding agent, and then carrying out C-N condensation reactions in the presence of a copper catalyst. The invention also provides a synthesis technology of mefenamic acid. The synthesis technology comprises the following steps: adding 2,3-dimethylaniline, strongly acidic cation exchange resin, o-chlorobenzoic acid, sodium bicarbonate, a copper catalyst, sodium acetate, and sodium ethyl benzene sulfonate into a condensation reaction tank to synthesize a first reaction liquid; then sequentially adding o-chlorobenzoic acid, sodium bicarbonate, and a copper catalyst into the first reaction liquid, dropwise adding liquid alkali to synthesize a second reaction liquid, adjusting the pH value of the second reaction liquid to obtain a condensation liquid, and finally subjecting the condensation liquid to filtering, decoloring, and purification to obtain mefenamic acid. The provided mefenamic acid synthesis technology has the advantages of few byproducts, high yield, safety, environment-friendliness, energy saving, improved efficiency, and simple operation.
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Paragraph 0054; 0055; 0056
(2017/03/08)
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- Synthesis method of mefenamic acid
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The invention discloses a synthesis method of mefenamic acid. The method comprises the following steps: by using o-chloro-benzoic acid as a raw material, salifying by using a non-proton polar solvent in the presence of an acid-binding agent to obtain o-chloro-benzoate; and under the action of a dehydrating agent, carrying out condensation reaction on the o-chloro-benzoate and 2,3-dimethylaniline by using metal manganese powder or manganese salt as a catalyst, and acidifying to obtain the mefenamic acid. The synthesis method disclosed by the invention has the advantages of high reaction yield, high product quality and low production cost, and solves the problems of lower product yield and deep product color in the existing preparation method.
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Page/Page column 0029; 0030; 0032; 0034
(2018/02/04)
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- Copper(II)-Mediated Intermolecular C(sp2)-H Amination of Benzamides with Electron-Rich Anilines
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Despite significant progress, copper-catalyzed/mediated C-H amination reactions with electron-rich anilines remain an unsolved problem due to catalyst deactivation and deleterious side reactions. Herein, we report a copper(II)-mediated C(sp2)-H amination of benzamides with electronically neutral or electron-rich anilines. A dramatic influence of silver(I) and tetrabutylammonium bromide was observed on the reaction outcome. The present protocol also demonstrates the synthesis of a number of nonsteroidal anti-inflammatory drugs.
- Singh, Bijaya Kumar,Polley, Arghya,Jana, Ranjan
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p. 4295 - 4303
(2016/06/09)
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- Aminocyanation by the addition of N-CN bonds to arynes: Chemoselective synthesis of 1,2-bifunctional aminobenzonitriles
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An efficient aminocyanation by the direct addition of aryl cyanamides to arynes is described, enabling incorporation of highly useful amino and cyano groups synchronously via cleavage of inert N-CN bonds, affording synthetically useful 1,2-bifunctional aminobenzonitriles. The postsynthetic functionalization of the aminocyanation products allows diverse formation of synthetically important derivatives such as drug molecule Ponstan and fused heterocycles.
- Rao, Bin,Zeng, Xiaoming
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p. 314 - 317
(2014/01/23)
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- Design and synthesis of some new N-phenylanthranilic acids from highly sterically hindered anilines
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Some new N-phenylanthranilic acids were designed and synthesized from highly sterically hindered anilines in an efficient and convenient method using CuI as catalyst with microwave irradiation and conventional heating.
- Li, Zhenghua,Chen, Gang,Qiao, Shu,Liang, Ronghui,Lan, Cong,Xia, Zhining
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p. 1270 - 1279
(2013/04/10)
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- Synthesis, kinetics and pharmacological evaluation of mefenamic acid mutual prodrug
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A novel mutual prodrug (MA-P) consisting of mefenamic acid (MA) and paracetamol (P) has been synthesized as a gastrosparing NSAID, devoid of ulcerogenic side effects. The structure of synthesized drug was confirmed by elemental analysis, infrared spectroscopy, 1H NMR spectroscopy and mass spectrometry. The kinetics of ester hydrolysis was studied by HPLC at pH 2, pH 7.4 as well as in human plasma. The pharmacological activities (anti-inflammatory, analgesic and ulcerogenic) were evaluated for the synthesized drug. The ulcerogenic reduction in terms of gastric wall mucosa, hexosamine and total proteins were also measured in glandular stomach of rats. The results indicated that MA-P ester has better ulcer index than the parent drug.
- Shah, Kamal,Shrivastava, Sushant K.,Mishra, Pradeep
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p. 905 - 911
(2013/10/01)
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- Continuous polymerization device, method of transferring a polymer granules, and olefin polymerization method
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PROBLEM TO BE SOLVED: To provide a continuous polymerization apparatus for olefins in which a reactive gas accompanying polymer granules pulled out from an upstream vapor phase polymerization tank can readily be substituted in an arbitrary ratio with other gas and transferred to a downstream vapor phase polymerization tank and continuous vapor phase polymerization of olefin is advantageously practiced thereby, in continuous polymerization for olefins using the apparatus in which a plurality of vapor phase polymerization tanks are serially arranged. ?SOLUTION: The continuous polymerization apparatus for olefins uses a plurality of vapor phase polymerization tanks having a specific structure (see the figure) serially arranged. The figure exhibits one example of the relationship between a gas substitution tank and the vapor phase polymerization tank arranged in the upstream of the gas substitution tank. A fluidized bed is arranged in the interior of the upstream polymerization tank 1 and the gas substitution tank 2 is connected through a first transfer pipe 4 composed of a pulling-up nozzle 4a and connecting piping 4b to the lower part. ?COPYRIGHT: (C)2006,JPOandNCIPI ?
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- The triphenyltin(VI) complexes of NSAIDs and derivatives. Synthesis, crystal structure and antiproliferative activity. Potent anticancer agents
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The novel triphenyltin(IV) esters of flufenamic acid (1), Hflu, [Ph 3Sn(flu)] (2), and of [2-(2,3-dichlorophenylamino)benzoic acid] (3), Hdcpa, [Ph3Sn(dcpa)] (4) have been structurally characterized by means of vibrational and 1H, 13C NMR spectroscopic studies. The crystal and molecular structures of [SnPh3(dcpa)(DMSO)] 4a are described. The molecular structure of 4a reveals that the Sn atom has a distorted trigonal bipyramidal coordination geometry with equatorial phenyl groups and the carboxylate and dimethylsulfoxide oxygen atoms occupying axial positions. The crystal structure of 4a is self-assembled by C-H - -π and π-π stacking interactions. The in vitro cytotoxic activity of 1-4 and of the related non-steroidal anti-inflammatory drugs, NSAIDs, [2-(2,6- dimethylphenylamino)benzoic acid], Hdmpa (5), [Ph3Sn(dmpa)] (6), [2-(2,3-dimethylphenylamino)benzoic acid], mefenamic acid, Hmef (7) and [Ph 3Sn(mef)] (8) has been evaluated against the cancer cell lines MCF-7, T-24, A-549 and L-929. The ligands exhibited very poor cytotoxic activity against the four cancer cell lines. Complex 6 exhibits the highest activity and selectivity against A-549 and MCF-7 cancer cell lines and complex 8 the highest activity and selectivity against T-24 cancer cell line. The cytotoxic results indicate that coupling of Hdmpa and Hmef with R3Sn(IV) metal center results in complexes with important biological properties and remarkable cytotoxic activity, since they display IC50 values in a μΜ range better to that of the antitumor drug cis-platin. Complexes 6 and 8 are considered as excellent antitumor compounds and the results of this study represent the discovery of triphenyltin(IV)esters as a potential novel class of anticancer agents.
- Dokorou, Vaso,Primikiri, Alexandra,Kovala-Demertzi, Dimitra
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scheme or table
p. 195 - 201
(2012/01/13)
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- A highly efficient precatalyst for amination of aryl chlorides: Synthesis, structure and application of a robust acenaphthoimidazolylidene palladium complex
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A robust palladium NHC complex was synthesized and exhibits exceptional activity and selectivity as a precatalyst in the amination of aryl chlorides and tolerates a wide range of substrates at low catalyst loadings.
- Tu, Tao,Fang, Weiwei,Jiang, Jian
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supporting information; experimental part
p. 12358 - 12360
(2011/12/15)
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- A simple and environmentally friendly method for the synthesis of N-phenylanthranilic acid derivatives
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A simple, efficient and environmentally friendly method for the synthesis of N-phenylanthranilic acid derivatives by the copper acetate catalysed reaction of o-halobenzoic acid with anilines using sodium acetate as base and water as media is described.
- Girisha, Hanakere R.,Srinivasa, Gejjalagere R.,Gowda, D. Channe
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p. 342 - 344
(2007/10/03)
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- Discovery of a potent, selective protein tyrosine phosphatase 1B inhibitor using a linked-fragment strategy
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Protein tyrosine phosphatase 1B (PTP1B) is an enzyme that downregulates the insulin receptor. Inhibition of PTP1B is expected to improve insulin action, and the design of small molecule PTP1B inhibitors to treat type II diabetes has received considerable attention. In this work, NMR-based screening identified a nonselective competitive inhibitor of PTP1B. A second site ligand was also identified by NMR-based screening and then linked to the catalytic site ligand by rational design. X-ray data confirmed that the inhibitor bound with the catalytic site in the native, "open" conformation. The final compound displayed excellent potency and good selectivity over many other phosphatases. The modular approach to drug design described in this work should be applicable for the design of potent and selective inhibitors of other therapeutically relevant protein tyrosine phosphatases.
- Szczepankiewicz, Bruce G.,Liu, Gang,Hajduk, Philip J.,Abad-Zapatero, Cele,Pei, Zhonghua,Xin, Zhili,Lubben, Thomas H.,Trevillyan, James M.,Stashko, Michael A.,Ballaron, Stephen J.,Liang, Heng,Huang, Flora,Hutchins, Charles W.,Fesik, Stephen W.,Jirousek, Michael R.
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p. 4087 - 4096
(2007/10/03)
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- Discovery and structure-activity relationship of oxalylarylaminobenzoic acids as inhibitors of protein tyrosine phosphatase 1B
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Protein Tyrosine phosphatase 1B (PTP1B) has been implicated as a key negative regulator of both insulin and leptin signaling pathways. Using an NMR-based screening approach with 15N- and 13C-labeled PTP1B, we have identified 2,3-dimethylphenyloxalylaminobenzoic acid (1) as a general, reversible, and competitive PTPase inhibitor. Structure-based approach guided by X-ray crystallography facilitated the development of 1 into a novel series of potent and selective PTP1B inhibitors occupying both the catalytic site and a portion of the noncatalytic, second phosphotyrosine binding site. Interestingly, oral biovailability has been observed in rats for some compounds. Furthermore, we demonstrated in vivo plasma glucose lowering effects with compound 12d in ob/ob mice.
- Liu, Gang,Szczepankiewicz, Bruce G.,Pei, Zhonghua,Janowick, David A.,Xin, Zhili,Hajduk, Philip J.,Abad-Zapatero, Cele,Liang, Heng,Hutchins, Charles W.,Fesik, Stephen W.,Ballaron, Steve J.,Stashko, Mike A.,Lubben, Tom,Mika, Amanda K.,Zinker, Bradley A.,Trevillyan, James M.,Jirousek, Michael R.
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p. 2093 - 2103
(2007/10/03)
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- Prodrugs of non-steroidal anti-inflammatory and carboxylic acid containing compounds
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Compounds of the formula: RC(O)O-spacer-OC(O)R′, wherein (i) RC(O)— is the acyl residue of an NSAID or other pharmaceutically active agent bearing a carboxylic acid function, (ii) spacer is Cn alkyl, (iii) n is from 1 to 6, and (iv) R′ is substituted or unsubstituted heteroaryl or heterocycle, and pharmaceutical compositions thereof.
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- Methods for use of GABAa receptor GABAergic compounds
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A method is disclosed for potentiating mammalian GABA A receptor responses to GABA. The receptor responses are potentiated according to the invention by contacting GABA A receptors with GABA and an effective amount of non-steroidal anti-inflammatory agents, in particular, fenamates and structurally related compounds.
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- Use of N,N-dimethylformamide as solvent in the synthesis of N-phenylanthranilic acids
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It is known that N-phenylanthranilic acids can be synthesized by Ullmann-Goldberg condensation in different conditions. This paper reports some parameters which influence the condensation and reports a general procedure for this reaction using N,N-Dimethylformamide as solvent.
- Pellon, Rolando F.,Carrasco, Ramon,Marquez, Tania,Mamposo, Taimirys
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p. 5107 - 5110
(2007/10/03)
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- Mucosal adhesive device for long-acting delivery of pharmaceutical combinations in oral cavity
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Mucosal adhesive devices are provided for use in the oral cavity for therapy against infections. The devices are dosage units which comprise a combination of antimicrobial agents such as antifungal agents and anti-inflammatory agents, optionally also a local anesthetic. The dosage units yield a gradual and relatively constant release of the pharmaceuticals over at least a 12-hour period.
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- Gastric preparation with sustained release
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A gastric preparation developed in order to solve the technical problems of conventional preparations, which is prepared by the bilayer packing technique and comprises 5 to 60%, desirably 10 to 40% of a rapid release portion which can establish the therapeutic level of a drug shortly after the administration and 95 to 40%, desirably 90 to 60% of a sustained release portion which has a specific gravity or 1 or less and can maintain a satisfactory release rate.
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- Combined anti-inflammatory agent
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A pharmaceutical composition for treating inflammatory diseases, comprising (A) an effective amount of hyaluronic acid or its salt, and (B) an effective amount of an anti-inflammatory agent. The composition exhibits a synergistic therapeutic effect on inflammations and is useful for treating inflammatory diseases, particularly diseases of joint with inflammation.
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- Ethoxycarbonyloxy ethyl esters of non-steroidal anti-inflammatory carboxylic acids and pharmaceutical compositions thereof
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Novel esters of the general formula STR1 in which STR2 is the acyl residue of a non-steroidal anti-inflammatory compound containing a carboxylic acid function. The novel esters are prepared by reacting an acide R--COOH when R is as above, with 1-haloethyl ethyl carbonate. There are also provided pharmaceutical compositions containing any of the said novel esters.
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- High molecular weight prodrug derivatives of antiinflammatory drugs
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Compounds of the formula 1, PS - O - A - (CH2)n- B - D (1), wherein PS-O represents an alkoxide residue of any of the free hydroxy groups of a polysaccharide (PS-OH) compound with molecular weight (Mw) of from 40,000 to 5,000,000 selected from dextran, carboxymethyl dextran, diethylaminoethyl dextran, starch, hydroxyet-hyl starch, alginates, glycogen, pullullan, agarose, cellulose, chitosan, chitin and carrageenan,A is a carbonyl group or absent,n is zero or a positive integer from 1 to 14,B is oxygen, a carbonyl group, NR wherein R is hydrogen or lower alkyl, or B is absent, and, D is (i) a group of the formula:, R1 - CO - (11), wherein R1-CO- represents the acyl residue of a carboxylic acid drug (R1-COOH) used in the treatment of inflammatory disorders; or (ii) a group of the formula:, R2 - O - (12), wherein R2-O- refers to the C-21 alkoxide residue of a known antiinflammatory steroid (R2-OH) or an alkoxide residue of any other drug or medicament containing a hydroxy functional group used in the treatment of inflammatory disorders; with the proviso that when A is absent, n is 0, and B is absent, then R1-CO- is different from the acyl residue of acetylsalicylic acid;, and non-toxic pharmaceutically acceptable acid addition salts thereof;, and non-toxic pharmaceutically acceptable cation salts thereof. Such compounds are biolabile prodrugs providing controlled release and prolonged duration of action of the parent active antiinflamma-tory agents locally at the administration site after intra-articular, intra-muscular, subcutaneous or extra-dural application while at the same time being highly stable in aqueous solution in the pH range 3--5. After oral administration of such prodrugs the parent drug is liberated selectively in the terminal ileum and the colon over an extended period of time.
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- THE USE OF ULTRASOUND IN THE SYNTHESIS OF N-ARYLANTHRANILIC ACIDS BY THE ULLMAN GOLDBERG REACTION
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Ultrasonic irradiation greatly improves the synthesis of N-arylanthranilic acids (shorter reaction times, higher purity of the final products) through the Ullman Goldberg reaction.
- Carrasco, Ramon,Pellon, Rolando F.,Elguero, Jose,Goya, Pilar,Paez, Juan Antonio
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p. 2077 - 2080
(2007/10/02)
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- Method for preventing renal papillary necrosis with prostaglandins
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The present invention provides a method for the prevention of renal papillary necrosis induced by non-steroidal anti-inflammatory compounds (NOSAC) comprising the administration of certain prostaglandins.
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- Structure-activity relationships in a series of anti-inflammatory N-arylanthranilic acids
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A large series of N-arylanthranilic acids has been prepared. Many of these compounds show high anti-inflammatory activity as measured by the anti-UV-erythema test. From this series have come the clinically useful nonsteroidal anti-inflammatory agents, flufenamic acid (Arlef), mefenamic acid (Ponstel), and the latest and most potent agent, N-(2,6-dichloro-m-tolyl)anthranilic acid (meclofenamic acid, Meclomen = the sodium salt). The structure-activity relationships of this series is discussed and a graphical representation is presented which allows the prediction of activity of new agents.
- Kaltenbronn,Scherrer,Short,Jones,Beatty,Saka,Winder,Wax,Williamson
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p. 621 - 627
(2007/10/02)
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- Esters and amides containing the 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indole-3-acetyl moiety
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Compounds of the formula STR1 wherein each X, which may be identical or different from the other X, is oxygen or imino; R1 is hydrogen, fluorine, chlorine or bromine; R2 and R3, which may be identical or different from each other, are each hydrogen; unsubstituted or mono-substituted alkyl of 1 to 6 carbon atoms, where the substituent is phenyl or dialkylamino with 1 to 3 carbon atoms in each alkyl moiety; pyridyl; or cycloalkyl of 5 to 7 carbon atoms; R2 and R3, together with each other and the nitrogen atoms to which they are attached, are pyrrolidino, piperidino, hexamethyleneimino, morpholino, N-aryl-piperazino or N-(alkyl of 1 to 3 carbon atoms)-piperazino; A is cycloalkylene of 5 to 7 carbon atoms; unsubstituted or substituted alkylene of 2 to 10 carbon atoms, where the substituents are one to two alkyls of 1 to 3 carbon atoms each, one to two carbalkoxys of 2 to 4 carbon atoms each, one to two phenyls, one to four hydroxyls, one halomethyl, one hydroxymethyl, one alkanoyloxy of 1 to 18 carbon atoms, one alkanoyloxymethyl of 1 to 18 carbon atoms in the alkanoyl moiety or one STR2 where R1, R2 and R3 have the meanings previously defined; or alkylene of 2 to 10 carbon atoms interrupted by oxygen, sulfur, sulfoxide, sulfonyl, phenyl, cyclohexyl, pyridyl, piperazino or unsubstituted or substituted imino, where the substituent on the imino group is alkyl of 1 to 6 carbon atoms, phenyl or phenylalkyl of 1 to 3 carbon atoms in the alkyl moiety; B is the acyl residue of an antiphlogistic carboxylic acid; and their non-toxic, pharmacologically acceptable acid addition salts. The compounds as well as their salts are useful as anti-inflammatories.
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- COMPOSES SULFURES HETEROCYCLIQUES. XCVI. REACTION DE L'HYDRAZINE SUR LES DIHYDRO-1,2 BENZOTHIAZINE-3,1 THIONES-4
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1-Alkyl-1,2-dihydro-3,1-benzothiazine-4-thiones 1, when reacting with hydrazine, give with a good yield a 1-alkyl-3-amino-2,3-dihydro-1H-quinazoline-4-thione-2, often together with a derivative of 1,3,4-thiadiazole-3. With 1-aryl-1,2-dihydro-3,1-benzothiazine-4-thiones, the main product of the reaction with hydrazine appears to be a 1-aryl-4-hydrazono-1,4-dihydro-2H-3,1-benzothiazine 4, sometimes with some amount of 3.On the contrary, when reacting with hydrazine, 1-alkyl (or 1-aryl)-1,2-dihydro-3,1-benzothiazin-4-ones lead to a 2-alkylamino (or arylamino)-benzohydrazide 5. By thermolysis 4 isomerizes into 2 which is accompanied by derivatives (3 and 7) of 1,3,4-thiadiazole.The structures of compounds 2, 4 and 7 have been studied by NMR and UV spectrometry.
- Legrand, Louis,Lozac'H, Noel
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p. 139 - 143
(2007/10/02)
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- Preparation of Ortho-Substituted Benzoic Acids by the Copper(II)-Catalyzed Reaction of Diphenyliodonium-2-carboxylate with Anilines and Other Nucleophiles
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Diphenyliodonium-2-carboxylate (DPIC) reacts readily in copper ion catalyzed condensations with a variety of nucleophiles to give ortho-substituted benzoic acids.These reactions occur at temperatures (80-100 deg C) below those at which benzyne formation and other side reactions become important.The nature of the Cu(II) catalysis appears to be different from the more common Cu(I) catalysis of diaryliodonium reactions in that high specificity in the displacement reaction is retained.Products obtained directly from DPIC condensations include N-anthranilic acid (5b), N-methyl-N-phenylanthranilic acid (5c), N-mesyl-N-(2,3-dimethylphenyl)anthranilic acid (5d), N-(3-chloro-2-methylphenyl)-N-tosylanthranilic acid (5e), and o-(2,3-dimethylphenoxy)benzoic acid (5f).Compound 5d has been cyclized to N-(2,3-dimethylphenyl)-1H-2,1-benzothiazin-4(3H)-one 2,2-dioxide (6).
- Scherrer, Robert A.,Beatty, Helga R.
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p. 2127 - 2131
(2007/10/02)
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