- Preparation method of acemetacin
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The invention discloses a preparation method of acemetacin. The preparation method comprises the following steps: (1) introducing hydrogen chloride into glacial acetic acid to prepare an acetic acid solution of hydrogen chloride; (2) adding acetic anhydride into the acetic acid solution of hydrogen chloride prepared in the step (1); (3) adding acemetacin tert-butyl ester into the hydrogen chloride-acetic acid-acetic anhydride mixed acidolysis solution obtained in the step (2), and stirring at a constant temperature; (4) after the reaction is finished, cooling, carrying out standing crystallization, filtering, and carrying out top-washing to obtain a crude product acemetacin; and (5) refining the crude product acemetacin to obtain the finished product acemetacin. The invention provides a preparation method of acemetacin, wherein the influence of moisture in raw materials on an acidolysis reaction of acemetacin tert-butyl ester is eliminated on the premise of adopting the existing equipment, so that the product yield is increased, the production cost is lowered, and the economic benefit is improved.
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Paragraph 0002; 0011-0014
(2020/12/05)
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- Preparation method of acemetacin
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The invention discloses a synthesis method of acemetacin. The synthesis method includes the steps that A, acemetacin benzyl ester is prepared according to the patent US4600783; B, the acemetacin benzyl ester is dissolved in a solvent, wherein the solvent is one of acetonitrile, methylbenzene and dichloromethane, a benzyl kation scavenging agent is added, the scavenging agent is one of anisole, phenol and N,N-dimethylaniline, and a solution A is obtained; C, aluminum chloride is added into the solvent, the prepared solution A is added at zero temperature, and the materials are stirred at normaltemperature; D, after the reaction is completed, a reaction mixture is poured into ice water, the materials are stirred and then filtered, and crude acemetacin is obtained; E, the obtained crude acemetacin is recrystallized according to the volume ratio of acetone to water being 2:1, vacuum drying is carried out, and the pure acemetacin is obtained. The method is easy to carry out, easy and convenient to operate and suitable for large-scale preparation, the price of aluminum chloride is low, no dechlorinated byproducts are generated, the purity of the acemetacin can reach and be larger than 99.8% only through one step of simple recrystallization, and no heavy metal residues are generated.
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Paragraph 0023-0028; 0030-0035; 0037-0042; 0044-0049; 0051-0
(2018/09/12)
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- Chemoselective ester/ether C–O cleavage of methyl anisates by aluminum triiodide
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The aluminum triiodide mediated chemoselective ester/ether C–O cleavage of methyl anisates was investigated. o-Anisate undergoes ether cleavage at low temperatures in carbon disulfide, cyclohexane and acetonitrile. Further cleavage of the ester group occurs at elevated temperatures to afford salicylic acid. The cleavage of p-anisate is solvent-dependent. In cyclohexane, the ester and ether groups were cleaved non-selectively to give equimolar amounts of p-anisic acid and methyl p-hydroxybenzoate. The ester group was preferentially cleaved in acetonitrile, compared to ether group cleavage in carbon disulfide. The ester cleavage reaction was improved using pyridine as an acid scavenger additive. Reasons for the contrasting reactivity of anisates towards AlI3 were explored, and the methods were applied to cleavage of the tert-butyl ester of acemetacin which gave different products under these conditions.
- Sang, Dayong,Yi, Cuicui,He, Zhoujun,Wang, Jiahui,Tian, Juan,Yao, Ming,Shi, Hong
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supporting information
p. 1469 - 1472
(2018/03/13)
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- Preparation method for acemetacin
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The invention relates to a preparation method for an anti-inflammatory and anti-phlogistic analgesic medicament, in particular to a preparation method for acemetacin, and belongs to the technical field of chemical pharmacy. The method comprises the following steps: introducing hydrogen chloride into acetic acid to prepare acetic acid and hydrogen chloride acidolysis solution, adding acemetacin tert-butyl ester into the acidolysis solution, stirring at a constant temperature, performing an acid hydrolysis reaction, cooling after the reaction is ended, standing, crystallizing, filtering, performing top washing, and refining to obtain the finished product acemetacin.
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Paragraph 0008; 0009; 0010; 0011; 0012; 0013; 0014-0016
(2017/06/21)
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- Glucose promoiety enables glucose transporter mediated brain uptake of ketoprofen and indomethacin prodrugs in rats
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The brain uptake of solutes is efficiently governed by the blood-brain barrier (BBB). The BBB expresses a number of carrier-mediated transport mechanisms, and new knowledge of these BBB transporters can be used in the rational targeted delivery of drug molecules for active transport. One attractive approach is to conjugate an endogenous transporter substrate to the active drug molecule to utilize the prodrug approach. In the present study, ketoprofen and indomethacin were conjugated with glucose and the brain uptake mechanism of the prodrugs was determined with the in situ rat brain perfusion technique. Two of the prodrugs were able to significantly inhibit the uptake of glucose transporter (GluT1)-mediated uptake of glucose, thereby demonstrating affinity to the transporter. Furthermore, the prodrugs were able to cross the BBB in a temperature-dependent manner, suggesting that the brain uptake of the prodrugs is carrier-mediated.
- Gynther, Mikko,Ropponen, Jarmo,Laine, Krista,Lepp?nen, Jukka,Haapakoski, Paula,Peura, Lauri,J?rvinen, Tomi,Rautio, Jarkko
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supporting information; experimental part
p. 3348 - 3353
(2010/03/05)
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- Nitrosated nonsteroidal antiinflammatory compounds, compositions and methods of use related applications
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The invention describes novel nitrosated nonsteroidal antiinflammatory drugs (NSAIDs) and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated NSAID, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel compositions comprising at least one nitrosated NSAID, and at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one nitrosated NSAID, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent. The invention also provides methods for treating inflammation, pain and fever; for treating gastrointestinal disorders; for facilitating wound healing; for treating and/or preventing gastrointestinal, renal and/or respiratory toxicities resulting from the use of nonsteroidal antiinflammatory compounds; for treating inflammatory disease states and/or disorders; and for treating and/or preventing ophthalmic diseases and/or disorders.
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Page/Page column 52
(2010/11/30)
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- Process for the preparation of alkenyl esters of acemetacin
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The new indole derivatives of the formula STR1 in which R1 and R2 are identical or different and denote hydrogen or lower alkyl, R3 denotes hydrogen, lower alkyl or halogen and R4 and R5 are identical or different and denote hydrogen, lower alkyl or optionally substituted aryl, and R4 and R5 can also represent lower alkenyl, and wherein R2 and R5 can be linked by an alkylene bridge of the formula in which n represents the number 0 or 1, can be prepared by reacting an ammonium or phosphonium salt of the corresponding indolecarboxylic acid with a haloacetic acid allyl ester. The new compounds can be used to prepare acemetacin. The new indole derivatives possess a pharmacological action.
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- Preparation process of acemetacin
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A process for preparing acemetacin which process comprises removing a protecting group, which is other than tetrahydropyranyl group and is removable under acidic conditions, from an acemetacin ester represented by the formula STR1 wherein R means the protecting group, under the acidic conditions.
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- Process for preparing acemetacin
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Acemetacin is prepared by reaction of an indometacin with tert.-butyl halogenoacetate and subsequent cleavage with sulphuric acid and/or sulphonic acid.
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- Isobutylene polymer active compound release systems
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In a therapeutic system such as a plaster for administration of an active compound through the skin and comprising a covering layer which is essentially impermeable to the active compound an active compound reservoir layer and a protective layer which can be pulled off and which is essentially impermeable to the active compound, the improvement wherein the reservoir layer contains about 1-30% of active compound in an elastomer mixture comprising at least one of polyisobutylene, polybutadiene oil and paraffin oil, and a tackifying resin. Thereby the active compound can be released in regulated relatively large quantity over a prolonged period of time.
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- Indole derivatives, processes for their preparation, and their use as medicaments
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The invention relates to indole derivatives identified herein by Formula (I) and a method for their preparation. Also included in the invention are compositions containing said indoles and methods for their use as antiphlogistic agents.
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- Chemical structure and anti-inflammatory activity in the group of substituted indole-3-acetic acids
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The chemical structure of the indometacin molecule was systematically modified with the aim of producing a substance with increased anti-inflammatory activity and improved tolerance. In addition to the variations of the methylene group of the indole-3-acetic acid and substituents on the indole nucleus of indometacin, particular attention was paid to the modification of the carboxyl group of the acetic acid side chain. Among the indometacin esters, one derivative, the [1-(4-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetoxy] acetic acid (54), showed an activity approximately twice that of indometacin in the kaolin edema test in the rat paw. Chemical modification of the new compound 54 did not further improve the activity. These studies suggest that specific substitutions on the indole nucleus, in combination with the acetic acid side chain as in 1, and especially the acetoxy acetic acid side chain in 54 are responsible for the high anti-inflammatory activity of this class of substances. Several methods for the synthesis of acemetacin are described.
- Boltze,Brendler,Jacobi,Opitz,Raddatz,Seidel,Vollbrecht
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p. 1314 - 1325
(2007/10/02)
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