- Production method of cimetidine
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The invention relates to a production method of cimetidine, the production method comprises the following steps: (1) reacting 2-chloroethanol with thiocyanate to prepare an intermediate (I); (2) reacting the intermediate (I) with methylamine to prepare an intermediate (II); (3) oxidizing the intermediate (II) with oxyacetic acid to obtain an intermediate (III); (4) condensing the intermediate (III) and cyanamide to obtain an intermediate (IV); and (5) condensing the intermediate (IV) and imidazole mercaptan (V) to prepare cimetidine. The production method of cimetidine is provided, the production method can avoid the environmental pollution caused by the by-product methyl mercaptan generated in the existing cimetidine production, and is simple in production process, low in production cost and suitable for industrial production.
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Paragraph 0007; 0026; 0031-0032; 0037-0038; 0043
(2021/08/11)
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- Importance of the azole moiety of cimetidine derivatives for the inhibition of human multidrug and toxin extrusion transporter 1 (hmate1)
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Herein, we describe the design and synthesis of cimetidine analogs, as well as their inhibitory activity toward the human multidrug and toxin extrusion transporter 1 (hMATE1), which is related to nephrotoxicity of drugs. Cimetidine is the histamine H2-receptor antagonist, but also inhibits hMATE1, which is known to cause renal impairment. We designed and synthesized cimetidine analogs to evaluate hMATE1 inhibitory activity to reveal whether the analogs could reduce the inhibition of hMATE1. The results showed that all analogs with an unsubstituted guanidino group exhibited hMATE1 inhibitory activity. On the other hand, there was a clear difference in the hMATE1 inhibitory activity for the other compounds. That is, compounds with a methylimidazole ring exhibited hMATE1 inhibition, while compounds with a phenyl ring did not. The results suggest that the ability to form hydrogen bonds at the azole moiety is strongly involved in the hMATE1 inhibition.
- Shinya, Susumu,Kawai, Kentaro,Tarui, Atsushi,Karuo, Yukiko,Sato, Kazuyuki,Matsuda, Masaya,Kitatani, Kazuyuki,Kobayashi, Naoki,Nabe, Takeshi,Otsuka, Masato,Omote, Masaaki
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p. 905 - 912
(2021/09/06)
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- Preparation method of cimetidine
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The invention discloses a preparation method of cimetidine. The preparation method comprises the following steps of (1) condensing 2-(4-methylimidazole-4-yl) methyl thioethylamine hydrochloride and CS2 in the presence of alkali, and preparing an intermediate (I) under the action of a desulfurization reagent, (2) reacting the intermediate (I) with monomethylamine to prepare an intermediate (II), and (3) in the presence of a desulfurization reagent, carrying out amination on the intermediate (II) and cyanamide to prepare cimetidine.
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- Preparation method of cimetidine
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The invention provides a preparation method of cimetidine. The method comprises the steps of firstly, converting (5-methyl-1H-imidazole-4-yl) methanol into nitrate of (5-methyl-1H-imidazole-4-yl) methanol, and then reacting with N-cyano-N'-methyl-N''-mercaptoethylguanidine ether to prepare cimetidine. The reaction conditions are mild, the yield is high, by-products are few, the aftertreatment is simple, volatile methyl mercaptan is not generated, the environmental friendliness and safety are greatly improved, and the method is particularly suitable for industrial application to produce cimetidine.
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Paragraph 0010; 0033; 0035-0043
(2021/05/26)
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- Process for synthesizing cimetidine
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The invention provides a process for synthesizing cimetidine. According to the technology, cimetidine can be obtained through one-step condensation of 4-((2-aminoethyl)thiomethyl)-5-methylimidazole, the technological process is very simple, and particularly, compared with multi-step synthesis, the technological process is greatly simplified, and the cost is reduced; cyanamido dimethyl dithiocarbamate is not used, so that volatile methyl mercaptan is not generated, the problem of stink is avoided, and the environmental protection property and the safety are greatly improved.
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Paragraph 0021-0028
(2021/06/22)
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- Cimetidine synthesis process
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The invention relates to the technical field of biomedicine, in particular to a cimetidine synthesis process. The cimetidine synthesis process has high efficiency, damage to the human body and the environment can be reduced, and meanwhile the synthesis cost can be reduced. The synthesis process comprises the following steps: (1) mixing a first intermediate with a photocatalyst, and dissolving theobtained mixture in a reaction solvent; (2) adding a second intermediate to the reaction solution obtained in the step (1), and performing uniform mixing so as to obtain a clear solution; (3) using alight source to irradiate the clear solution obtained in the step (2), and performing coordinated stirring until it is shown through HPLC that the first intermediate reacts completely; and (4) performing concentration treatment so as to remove the solvent after completion of the reaction, and performing recrystallization by using water and isopropanol or ethanol so as to obtain cimetidine white powder.
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Paragraph 0048-0059
(2019/11/12)
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- Floating pharmaceutical composition comprising an active phase and a non-active phase
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The invention concerns a floating pharmaceutical composition consisting of at least a first phase comprising at least a high dose active principle combined with one or several carriers and at least a second phase comprising at least a gas-generating system. The invention also concerns tablets comprising such a pharmaceutical composition and a method for preparing such tablets.
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- Cimetidine granules coated with a partially hydrogenated vegetable oil
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A non-aqueous, chewable composition for oral delivery of unpalatable drugs is provided. The composition contains the drug intimately dispersed or dissolved in a pharmaceutically acceptable lipid that is solid at room temperatures. The composition also has a matrix that contains a granulating agent for the total composition and a rapid dispersal agent and optionally additives such as buffering agents, flavoring agents, surfactants and the like.
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- Granular product or tablet containing an effervescent system and an active pharmaceutical substance, as well as a method for its preparation
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In accordance with this invention there is provided a granular product with an effervescent system which comprises acid-sensitive pharmaceutically active substances, such as, for example, beta-carotene, cimetidine, ranitidine or cisapride, which is specially useful to prevent antacid action, having an acid-binding capacity below about 5meq, at a weight of about 1.6 to about 2.3 grams. The effervescent grains are made from carrier crystals of at least one solid, edible organic acid, preferably citric acid, and are present as a granular product, separate from the pharmaceutically active substance, and are coated with at least one layer of a water-soluble neutral substance which is able to bring about a melting point depression of the acid grains at their surface, such as, for example, a water-soluble polymer, a higher alcohol, a carbohydrate and/or a hydrocolloid. A second coating contains at least a part of the alkali and/or alkaline earth carbonate or bicarbonate provided for the total dosage.
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- Solid pharmaceutical compositions for oral administration with prolonged gastric residence
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Solid pharmaceutical compositions for oral administration, with prolonged residence in the stomach, consisting of one or more high density inorganic substances, one or more bioadhesive substances, an active ingredient - either as it is or mixed in a carrier system - as well as excipients, binders, lubricants and other materials commonly used in pharmaceutical formulations.
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- Dispersible cimetidine tablets
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There are described novel dispersible cimetidine tablets containing 30 to 90% by weight of one of the polymorphous modifications of cimetidine A, B or C, 5 to 55% by weight of one or more disintegrationg agents, 0.05 to 5.0% by weight of a surfactant, such as sodium lauryl sulphate together with other common adjuvants. The process for the manufacture of dispersible cimetidine tablets is effected on the basis of known methods by granulating the ingredients and by compressing the granulate to tablets. Dispersible tablets disintegrate when brought in contact with water at room temperature within less than 1 minute to yield a fine dispersion, which facilitates the oral application. Therefore such tablets are particularly suitable for certain groups of patients, especially for the aged and children. Dispersible tablets containing cimetidine excell by their improved rate of dissolution and good bioavailability.
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- Alpha-acyloxyketone derivatives
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Disclosed are alpha-acyloxyketone derivatives which are useful as intermediates for production of N-cyano-N'-methyl-N"-[2-{(5-methyl-1H-imidazol-4-yl)methylthio}ethyl]guanidine (common name: Cimetidine; Cimetidine applies hereinafter) and Cimetidine-related compounds which have an action of controlling secretion of gastric acid and are useful as a drug for treating gastric ulcer.
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- Process for producing a guanidine derivative
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The guanidine derivative represented by the formula [III], STR1 (commonly known under the name "Cimetidine") is produced by reaction of the compound represented by the formula [I], STR2 with a compound represented by the formula [II], STR3 wherein R1, R2, R3, R4, R5 and R6, is each hydrogen atom, a lower alkyl group, phenyl group, or a radical of --OR7 or --COOR7, in which R7 is hydrogen atom, a lower alkyl group or an alkali metal, followed by reaction with methylamine.
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- Process for preparation of guanidine derivative
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N-cyano-N'-methyl-N"-(2-(5-methyl-4-imidazolylmethylthio)ethyl)guanidine (Cimetidine), which is valuable as an agent for controlling secretion of gastric acid, is prepared in a high yield by reacting N-cyano-N'-methyl-N"-(2-(butane-2,3-dionyl)thioethyl)-guanidine as the starting compound with an ammonium salt of a carboxylic acid and formaldehyde.
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- Process for preparing H2 receptor antagonist ascorbate compounds
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H2 -receptor antagonist ascorbate compounds, derived from the lactone form of 3-ketohexuronic acid of Formula STR1 where (X) may be 1, 2 or 3 and (Y) may be 1 or 2, R1 and R2 are both hydrogen or R1 may be hydroxyl, R2 hydrogen or the O-alkylidene, 5,6-diacyl, 6-acyl derivatives thereof having two to sixteen carbon atoms, or a 6-phosphate, R3 being an organic base or a salt thereof having one or more basic functional groups, having H2 -receptor antagonist properties and capable of reacting with nitrous acid, and a process for the preparation of said compounds.
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- Cyanoguanidine derivative and process for preparation thereof
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Cyanoguanidine derivatives of formula (I) wherein R is lower alkyl and R′ is hydrogen or a lower alkyl are precursors for the synthesis of N-cyano-N′--methyl-N″-[2-{(5-methyl-1H-imidazol-4-yl)methylthio]ethyl]--guanidine (cimetidine) or homologues thereof. These cyanoguanidine derivatives are prepared by reacting a haloketone derivative with an ammonium salt and a lower alkanoic acid salt or by reacting another cyanoguanidine derivative with an ammonium salt.
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- CIMETIDINE Z, A NEW CRYSTAL MODIFICATION OF CIMETIDINE
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The invention relates to a new crystal modification of N-methyl-N'-{2-(5-methylimidazol-4-yl)-methylthio!-ethyl}-N"-cyanoguanidine (cimetidine), a histamine H-2 receptor antagonist having the Formula (I) STR1 as well as to a process for preparing same. In the description, this new modification is named N-methyl-N'-{2-(5-methylimidazol-4-yl)-methylthio!-ethyl}-N"-cyanoguanidine Z (cimetidine Z). "
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- Process for preparing the H2 -receptor antagonist cimetidine
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Cimetidine, namely N-cyano-N'-methyl-N"-[2-((4-methyl-5-imidazolyl) methylthio) ethyl] guanidine which is useful as an antagonist of H2 -receptor is prepared by reacting 4-methyl-5-[(2-aminoethyl) thiomethyl] imidazole, which is obtained by the reaction of 4-methyl-5-hydroxymethylimidazole on 2-aminoethanethiolsulfuric acid, with O-alkyl-S-alkyl-cyanothioimidocarbonate to give N-cyano-N'-[2-((4-methyl-5-imidazolyl) methylthio) ethyl]-O-alkylisourea, which is reacted with monomethylamine. According to the present process, cimetidine can be prepared in good yield and desired purity with very reduced amount of methyl mercaptan released from the reaction.
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- Disulfide intermediate for cimetidine
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A process for preparing cimetidine by sulfur extrusion from N-cyano-N'-methyl-N"-[2-(5-methyl-4-imidazolylmethyldithio)ethyl]guanidine.
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- Process for preparing an imidazole derivative
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This invention relates to new processes for preparing an imidazole derivative, i.e. cimetidine, by (1) reacting an imidazolylmethylthioethylamine with an amidine or (2) reacting a N-cyano-N'-imidazolylmethylthioethyl formamidine with methylamine or (3) reacting a N-methyl-N'-imidazolylmethylthioethyl formamidine with cyanamide.
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- Synthesis of cimetidine
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A simple and economical synthesis of cimetidine is described. It is based on the reaction of 4-halomethyl-5-methylimidazole with N-cyano-N'-methyl-N''-(2 mercaptoethyl)guanidine in water-ethanol at pH 9.0 ± 0.3. Pure crystalline cimetidine is obtained in about 75% yield.
- Kairisalo,Honkanen
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p. 688 - 690
(2007/10/02)
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- Process for preparing 5-methyl-4-imidazolecarboxylic acid esters
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A process for the preparation of 5-methyl-4-imidazolecarboxylic acid esters from acetoacetic acid esters. The products of this process are useful as intermediates for preparing cimetidine.
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- NEW SYNTHESES OF 2-CYANO-1-METHYL-3-THIO>ETHYL>GUANIDINE (CIMETIDINE)
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A new synthesis of 2-cyano-1-methyl-3-thio>ethyl>guanidine, 6 (cimetidine) utilizing the aziridine derivative 5 as a two-carbon one-nitrogen synthon, is reported.Attempts to prepare the key intermediate 5 via azirid
- Toso, Roberto,Mihalic, Mladen,Sega, Alessandro,Sunjic, Vitomir
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p. 345 - 350
(2007/10/02)
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- Process for preparing N-cyano-N'methyl-N"-{2-[(4-methyl-5-imidazolyl)-methylthio]-ethyl} guanidine
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A process of preparing STR1 by reacting 4-thiomethyl-5-methyl imidazole with N-cyano-N'-methyl-N"-(2-chloroethyl) guanidine in a two-phase system under the conditions of phase transfer catalysis.
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- Imidazolemethylphosphonium salts
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New imidazolemethylphosphonium salts having a degradable group at the 2-position which are useful intermediates for preparing histamine H2 antagonists.
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- Process for preparing 4-substituted imidazole compounds
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A process for preparing 4-(oxy, thio or amino)methylimidazole compounds via displacement of the trisubstituted phosphonium group from 4-(trisubstituted phosphonium)methylimidazole compounds is disclosed.
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- PROCESS FOR PREPARING HETEROCYCLICALKYLTHIOALKYL-N-CYANOGUANIDINES
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Process for preparing heterocyclicalkylthioalkyl-N-cyanoguanidines and thioureas by treating a heterocyclicalkyl derivative with a mercaptoalkyl-N-cyanoguanidine or thiourea. Two specific products are N-cyano-N'-methyl-N"-2-((5-methyl-4-imidazolyl)methylt
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- PROCESS FOR PREPARING N-CYANOGUANIDINES
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Process for preparing N-cyanoguanidines by treating N-(loweralkyl)-N'-cyano-isothioureas with an amine and a heavy metal salt. A specific product is N-cyano-N'-methyl-N"-2-((5-methyl-4-imidazolyl) methylthio) ethyl!guanidine, useful as a histamine H 2-antagonist. "
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- Process for preparing 4-(hydroxymethyl)imidazole compounds
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An improved process for the preparation of 4-(hydroxymethyl)imidazoles by reducing 4-imidazolecarboxylic acid esters using an alkali metal or calcium in liquid ammonia with an additional proton source provided during the reaction or upon workup.
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- PHARMACOLOGICALLY ACTIVE GUANIDINE COMPOUNDS
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The compounds are substituted thioalkyl-, aminoalkyl-and oxyalkyl-guanidines which are inhibitors of histamine activity.
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- PHARMACOLOGICALLY ACTIVE GUANIDINE COMPOUNDS
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The compounds are substituted thioalkyl-, aminoalkyl-and oxyalkyl-guanidines which are inhibitors of histamine activity.
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- Process of reduction
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An electrochemical process for preparing 4-(hydroxymethyl)-imidazoles, which are useful as chemical intermediates.
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- PHARMACEUTICAL COMPOSITIONS AND METHODS OF INHIBITING H-1 AND H-2 HISTAMINE RECEPTORS
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Pharmaceutical compositions and methods of inhibiting H-1 and H-2 histamine receptors by administering an antihistamine and an H-2 histamine receptor inhibitor. Exemplary of the antihistamine in the compositions and methods of this invention is mepyramine and exemplary of the H-2 histamine receptor inhibitor is N-cyano-N'-methyl-N"-2-((4-methyl-5-imidazolyl)-methylthio)ethyl!guanidine. "
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