- Synthesis and biological evaluation of: N 6derivatives of 8-azapurine as novel antiplatelet agents
-
Two series of novel N6 derivatives of 8-azapurine I and II were designed as antiplatelet agents. Series I and II were N6 amino derivatives and N6 hydrazone derivatives of 8-azapurine, respectively. The compounds were synthesized in acceptable yields via conventional procedures, including nucleophilic substitution, diazotization, and amination or hydrazonation with amino alcohol and 4,6-dichloropyrimidine as starting materials. To assess the ability of the synthesized compounds as antiplatelet agents, the ADP-induced platelet aggregation assay of Born was performed both in vitro and in vivo using ticagrelor as a reference control substance. The analysis of the structure-activity relationship and molecular docking were also discussed in detail. The results demonstrated that series I and II compounds exhibited antiplatelet activity in vitro and IIh was the most active compound (IC50 = 0.20 μM) among the target compounds, being almost 4-fold better than ticagrelor (IC50 = 0.74 μM). For a preliminary assessment of the safety profile, a bleeding test (mouse tail) and a single-dose toxicity test were conducted. The use of compound IIh resulted in a shorter bleeding time, less blood loss and lower acute toxicity compared to ticagrelor. In addition, a molecular docking study was performed to investigate the binding capacity and binding mode between IIh and P2Y12. This journal is
- Tian, Nana,Wang, Juan,Wang, Yeming,Yan, Hong,Zhao, Zhichang
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p. 1414 - 1427
(2021/11/09)
-
- NEW USE OF TRIAZOLO[4,5-D]PYRIMIDINE DERIVATIVES
-
Triazolo[4,5-d]pyrimidine derivatives of formula (I) for use in prognosis and/or diagnosis of bacterial infection in a host mammal and method of imaging thereof. Formula (I) wherein R1 is C3-5 alkyl optionally substituted by one or m
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Page/Page column 13; 15
(2021/01/29)
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- Preparation process of ticagrelor intermediate
-
The invention discloses a preparation process of a ticagrelor intermediate. The process comprises the following steps of dissolving 4,6-dichloro-2-(propylthio)-5-aminopyrimidine and sodium bicarbonatein water at a temperature of 15-25 DEG C; performing heating, adding an aqueous solution of 2-[[(3aR, 4S, 6R, 6aS)-6-amino-2, 2-dimethyltetrahydro-3aH- cyclopentadiene [d] [1,3]-dioxol-4-yl] oxy]-1-ethanol (III) or a salt thereof, and performing stirring at a constant temperature until a reaction is finished; stopping heating, cooling a reaction mixture, adding ethyl acetate, separating liquid, and washing an organic phase with water; stirring the organic phase, slowly dropwise adding n-hexane at a certain temperature, and separating out a solid to obtain the intermediate. According to the process, the use of excessive organic base such as triethylamine is avoided, the cheap and easily available sodium bicarbonate is used, the production cost is low, the reaction time is short, three wastes are few, and the obtained ticagrelor intermediate is the solid with the high purity, is high in yield and is more suitable for industrial production.
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Paragraph 0014; 0026-0028
(2020/12/09)
-
- Production process of ticagrelor fine product
-
The present invention discloses a production process of a ticagrelor fine product. The process comprises the steps of adopting 4,6-dichloro-5-amino-2-propylthiopyrimidine (IIa) and a compound (IIb) asstarting raw materials, and carrying out five processes including a substitution process I, a cyclization process, a substitution process II, a hydrolysis process and a refining process to finally obtain the ticagrelor fine product. The method provides a ticagrelor production process, uses cheap and easily available raw materials, has the advantages of low production cost, simple reaction conditions, convenient post-treatment, high yield and high product purity, and is more suitable for industrial production.
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Paragraph 0020-0022; 0027-0029; 0034-0036
(2020/12/09)
-
- Improved preparation method of ticagrelor intermediate (by machine translation)
-
Step, Step: Reaction 1: Reaction of Compound 1 and Compound 2 with ethylene glycol, triethylamine under nitrogen protection, to obtain ticagrelor intermediate product, wherein the mixed solvent is an alcohol solvent, weak alkaline agent, in which the purity of intermediate product, is not less than, and the content of impurities, is not more than, in step (II) of inert gas protection descent temperature; to obtain ticagrelor intermediate. 2: The mixed solvent is obtained by filtering, organic layers under reduced pressure . The product obtained in Step 1, is obtained by adding an inert solvent (II), (II) and purifying/water, to, obtain a (II) ticagrelor intermediate product, obtained 99.2%, by stirring and dissolving, 3 into 0.05%; an active carbon decolorizing, filtrate .] 99.2%, filtering method of an 3 intermediate product thereof, 0.05%. is carried out in an inert gas protection falling temperature. (by machine translation)
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Paragraph 0037-0048
(2020/03/17)
-
- Synthesis of ticagrelor analogues belonging to 1,2,3-triazolo[4,5-d]pyrimidines and study of their antiplatelet and antibacterial activity
-
Based on the recent observation that the antiplatelet agent ticagrelor and one of its metabolite exert bactericidal activity against gram-positive bacteria, a series of 1,2,3-triazolo[4,5-d]pyrimidines structurally related to ticagrelor were synthesized and examined as putative antiplatelet and antibacterial agents. The aim was to assess the possibility of dissociating the two biological properties and to find novel 1,2,3-triazolo[4,5-d]pyrimidines expressing antiplatelet activity and devoid of in vitro antibacterial activity. The new compounds synthesized were known metabolites of ticagrelor as well as structurally simplified analogues. Some of them were found to express antiplatelet activity and to lose the antibacterial activity, supporting the view that the two activities were not necessarily linked.
- Goffin, Eric,Jacques, Nicolas,Lancellotti, Patrizio,Musumeci, Lucia,Nchimi, Alain,Pirotte, Bernard,Oury, Cécile
-
-
- Preparation method of ticagrelor
-
The invention provides a preparation method of ticagrelor. According to the preparation method, a compound shown in a formula (i) is used as a raw material, and the ticagrelor is prepared by means ofcondensation, ring formation, condensation and deprotection; the preparation method is simple and convenient in technological process and easy to operate, thus being suitable for large-scale production; furthermore, the preparation method provided by the invention is mild in synthesis conditions, high in product yield and good in product purity, can effectively control the preparation cost, and reduces the medication burden of patients.
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Paragraph 0056-0060; 0065; 0066-0070
(2019/04/30)
-
- Preparation method of ticagrelor
-
The invention relates to synthesis of a pharmaceutical compound and in particular relates to a preparation method of ticagrelor. The method disclosed by the invention comprises the steps as follows: step 1, synthesizing an intermediate Im-1; step 2, synthesizing an intermediate Im-2; step 3, synthesizing an intermediate Im-3; step 4, synthesizing a crude product Im-4; and step 5, carrying out refining, namely recrystallizing the crude product of ticagrelor by using 10-15 times of mixed solution of dichloromethane and tertiary butanol, and carrying out washing, filtering and drying to obtain arefined product of ticagrelor, wherein the volume ratio of dichloromethane to tertiary butanol in the mixed solution of dichloromethane and tertiary butanol is 1:(2-3).
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Paragraph 0124-0140
(2018/08/28)
-
- Synthesizing method of ticagrelor
-
The invention relates to synthesis of a medicine compound, in particular to a synthesizing method of ticagrelor. The synthesizing method comprises the following steps of S1, synthesizing an intermediate Im-1; S2, synthesizing an intermediate Im-2; S3, synthesizing an intermediate Im-3; S4, synthesizing a crude product Im-4; S5, refining: recrystallizing a crude product of the ticagrelor by a mixedsolution of dichloromethane and tertiary butanol, washing, filtering, and drying, so as to obtain a refined product of the ticagrelor.
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Paragraph 0124; 0131; 0132; 0133; 0134; 0135; 0136-0140
(2018/07/30)
-
- Preparation method of high-purity ticagrelor
-
The invention discloses a preparation method of high-purity ticagrelor. The preparation method comprises the following steps: preparing intermediates TG-1, TG-2, TG-3 and TG-4; and refining the ticagrelor. According to the preparation method, matching of reactants is adjusted, the reaction time and temperature are optimized, and a post-processing manner is adopted; a specific catalyst and a specific devitrification solvent are selected, so that the reaction efficiency of the intermediates is improved, the reaction time is shortened and the purity of the intermediates is improved; after a crudeproduct of the ticagrelor is obtained, different devitrification solvents and a staged crystallization process are adopted to obtain the ticagrelor with high purity, so that the production cost is reduced, the advantages of being high efficiency and clean in production are achieved, and the operability is strong; and the purity of the obtained ticagrelor product is not lower than 99.8%, and no single impurity exceeds 0.06%.
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Page/Page column 8-17
(2019/01/06)
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- A cyclopentyl pyrimidine compounds of the solvent-free preparation method
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The invention relates to a solvent-free preparation method of a cyclopentyl pyrimidine compound and belongs to the field of a chemical preparation method. According to the solvent-free preparation method of the cyclopentyl pyrimidine compound (SM-C), SM-A is reacted with SM-B without a solvent under an alkaline condition to generate the SM-C. According to the method provided by the invention, an organic solvent is not used so that the production cost is reduced, the environmental pollution is reduced, the post-treatment is simplified and removal of organic solvent is not needed; a solvent-free reaction is carried out so that the reaction volume is greatly reduced and the production capability of equipment is improved; the solvent-free reaction is carried out so that the reaction concentration is improved, the conversion rate of raw materials of the reaction is improved, the reaction speed is improved and the reaction time is greatly shortened; meanwhile, the reaction can produce under a normal-pressure condition and a high-pressure reaction kettle is not needed so that the production is facilitated.
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Paragraph 0022-0031
(2018/11/22)
-
- Conformational analysis of ticagrelor: effect of noncovalent interaction on conformational population
-
In order to track the source of duplicated peaks in the 1H-NMR spectrum of Ticagrelor, variable-temperature NMR (VT-NMR) experiment was carried out with temperature increasing from 300 to 343?K. The result showed that the phenomenon was brought forth by coexistence of conformational isomers. Subsequently, conformational search was carried out by molecular mechanics (MM) stimulations associating with quantum mechanics (QM) calculations. The results revealed that the isomers resulting in duplicated proton peaks were introduced by the rotation of 2,4-diflurophenyl group on C3’position of cyclopropyl. Finally, noncovalent interaction (NCI) topological analysis of the conformers exhibited that CH-π interactions and H-bonds play important roles in controlling the population of conformers of ticagrelor.
- Fan, Qiangwen,Tan, Hongbo,Wang, Yeming,Song, Xiuqing,Yan, Hong
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p. 1663 - 1670
(2018/07/03)
-
- An NMR and DFT investigation on the interconversion of 9-substituented-N 6-hydrazone-8-azaadenine derivatives: proton migration or conformational isomerization?
-
A newly synthesized N6-arylhydrazone-8-azaadenine derivatives (1) showed significant differences in NMR spectra with previously synthesized analogues, specifically, the hydrogens of N1’H and C3’H in all the titled compounds showed two groups of signals in their 1H-NMR spectra. In order to investigate whether the duplication of proton signals were related to a mixture of conformational isomers which rotated around C-N1’ bond or configurational isomers which resulted from proton migration, variable temperature NMR and 2D-NOESY experiments were carried out in conjunction with density function theory (DFT) calculations at the B3LYP/6-311G (d,p)//B3LYP/6-31G (d,p) level. The results indicated that it was the conformational isomerism rather than hydrogen transfer that induced the reproduction of proton signals, which was attributed to lower barrier energy and larger rate constant of the former process.
- Fan, Qiangwen,Wang, Yeming,Yan, Hong
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p. 871 - 879
(2018/02/16)
-
- Preparation process for ticagrelor
-
The invention discloses a preparation process for ticagrelor. By adding organic weak base to neutralize acetic acid and acetic acid generated from degrading of ethyl acetate in the process of preparing the ticagrelor, oxide impurities generated in ticagrelor final products are avoided; a test proves that oxide impurity sulphone and sulfoxide in original final products are removed effectively; and according to the preparation process, the product quality is improved greatly, and the process is simple, feasible and suitable for industrialized production.
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-
Paragraph 0047; 0048; 0058; 0059; 0069; 0070
(2017/08/28)
-
- Synthesis method of ticagrelor
-
The invention discloses a synthesis method of ticagrelor. The method comprises the steps of 1, adding thiourea and alkali to a solution where bi-aminomalonic acid diethyl ester is dissolved, wherein the mole ratio of bi-aminomalonic acid diethyl ester, thiourea and alkali is 1:(1.0-1.5):(2-2.3), and performing a reaction under the protection of nitrogen at 25-100 DEG C for 5-72 h to obtain a compound 2; 2, adding bromopropane to a solution where the compound 2 is dissolved at -2 DEG C-2 DEG C, and conducting stirring at 25-50 DEG C for 2-72 h to obtain a compound 3; 3, adding organic alkali and a chloride agent to the compound 3, raising the temperature to 20-75 DEG C, and performing a reaction for 3-8 h to obtain a compound 4; 4, synthesizing ticagrelor, wherein the compound ticagrelor is obtained by conducting substitution, loop closing, substitution and a hydrolysis reaction on the compound 4 (4,6-dichloro-2-propylthiopyrimidine-5-amine), the operation steps are greatly simplified, and the yield is drastically increased. The synthesis method of ticagrelor is simple in operation and high in reaction yield.
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-
-
- A [...] crystallization and containing the pharmaceutical compositions
-
The invention provides a ticagrelor crystal and a medicinal composition comprising the same. The purity of the ticagrelor crystal is greater than 99 percent, and an impurity N is less than 0.1 percent. The crystal is prepared by adopting a one-pot method and is obtained by adopting a further crystal refining method. By adopting the methods, the ticagrelor with the purity being obviously improved can be obtained, and the raw material and medicinal composition with excellent quality are further acquired.
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Paragraph 0048-0051; 0062
(2017/10/06)
-
- Process suitable for ticagrelor industrial production
-
The invention discloses a process suitable for ticagrelor industrial production, which comprises the following steps of step 1, using tartrate of a compound III as a starting material, using sulfolane and diisopropylethylamine as a solvent, and reacting for 3 hours at 105-108DEG C; step 2, using mild tetrahydrofuran and oxalic acid dihydrate as a solvent, and using diisopropylethylamine to replace triethylamine in an original study patent, thereby reducing reaction time, and reducing a potential genotoxicity risk of the triethylamine; and step 3, an optimized reaction temperature in the invention is -5-0DEG C; using methyl tertiary butyl ether to replace ethyl acetate as an extraction agent; using an ethyl acetate and cyclohexane mixing solvent to replace a methyl tertiary butyl ether and cyclohexane mixing solvent to purify a finished product; wherein polarity of the ethyl acetate is greater than that of the methyl tertiary butyl ether; using the methyl tertiary butyl ether during extraction and using the ethyl acetate during purification may remove impurities and improve purity to the greatest extend.
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-
Paragraph 0033; 0034; 0035; 0036
(2017/07/20)
-
- Improved method for preparing ticagrelor
-
The invention discloses an improved method for preparing ticagrelor. The method comprises the following steps of conducting an acid binding agent reaction kettle heating reaction on ethylene glycol, FTG-SM1, FTG-SM2 and triethylamine; then conducting extracting, concentrating and methyl alcohol/water salify crystallization to obtain TFG-3; conducting diazotization, loop closing, an FTG-SM3 substitution reaction and acidification protecting group separation continuous reaction on FTG-3 in methylbenzene to obtain a coarse product of ticagrelor; conducting recrystallization on the coarse product to obtain a finished product. According to the improved method for preparing ticagrelor, cheap reagents and raw materials are utilized, and the technology cost is lowered; regarding refining of a middle body FTG-1, a methyl alcohol/water system is adopted, and the content of related substances is effectively controlled; by conducting three-step reaction continuous compounding, solvents are saved, the operation is simplified, and the technology cycle is shortened; the dose of the solvent is less, the pollution is lowered, and the method is environmentally friendly. The improved method for preparing ticagrelor is simple and safe in operation condition and simple in after-treatment, the product is easy to obtain, high in yield and high in purity. The technology cost is low, and the improved method is suitable for industrial large-scale production.
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Paragraph 0032; 0043; 0044-0055; 0095-0107
(2017/12/06)
-
- A for the card Grey crystal form and its preparation method
-
The invention relates to a crystal form of an anti-thrombotic medicament ticagrelor, a preparation method for the crystal form, a medicinal composition containing the crystal form and an application of the crystal form to the preparation of the anti-thrombotic medicines. The crystal form of ticagrelor is a crystal form A with a structure as shown below. A Cu-Kalpha radiation mode is adopted. An X-ray powder diffraction pattern of the crystal form A, represented by an angle 2Theta has characteristic diffraction peaks at the following positions: 6.2+/-0.2 degrees, 11.5+/-0.2 degrees, 15.0+/-0.2 degrees and 20.6+/-0.2 degrees. The crystal form A of ticagrelor has the advantages of convenience of the preparation method, high stability and preparation adaptability and the like, so that the crystal form A is industrially practical.
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Paragraph 0084-0086
(2017/08/25)
-
- 6-hydrazone radical-8-aza-purine compound and preparing method and application thereof
-
The invention relates to a 6-hydrazone radical-8-aza-purine compound and a preparing method and an application thereof and belongs to the fields of preparation of novel compounds and medicine application. The general molecular formula of the compound is shown in the description, wherein R1 is hydroxide radical, methylol group and hydroxyethoxy, R2 is hydrogen, hydroxide radical, and fluorine, R3 is methyl, ethyl, propyl and 3,3-trifluoropropyl group, and R4 is aryl group, substitutional aryl group, ceteroary, and substitutional ceteroary. A midbody is used as reaction substrate, wherein the formula of the midbody is shown in the description, the midbody and a hydrazine and aldehydes compound are subjected to a condensation reaction, and the 6-hydrazone radical-8-aza-purine compound is obtained. According to the novel 6-hydrazone radical-8-aza-purine compound, the antiplatelet aggregation activity is high, the bleeding side effect is low, and the compound can be used for preparing the antiplatelet aggregation medicine and preventing and treating the related thrombotic disease.
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Paragraph 0070-0074
(2017/09/02)
-
- A process for the preparation of intermediates for card Grey
-
The invention provides a preparation method for ticagrelor intermediate. The preparation method comprises the following steps: using tertiary amine as an acid-binding agent, performing N-aromatic alkylated reaction on a compound (II) or salt of the compound (II) and a compound (III) in an appropriate solvent at the temperature of 90 to 130 DEG C, and generating a compound (I). The preparation method provided by the invention has the following advantages: side reaction of impurity generated in the reaction of the solvent and raw materials can be effectively avoided, the preparation method has obvious superiority on product quality, the raw material conversion rate and productive rate of the product compound (I) are improved, the productive rate is 85.8% to 89.5%, the HPLC purity of the product is 98.8% to 99.5%, the preparation method has obvious superiority on raw material conversion rate, sealed reaction is not needed, equipment is simple, a pressure-resistant reaction kettle is not needed to be used, and compared with the prior art, the preparation method has obvious superiority on equipment use.
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Paragraph 0065; 0066; 0067
(2016/10/07)
-
- SOLID FORM OF INTERMEDIATE OF TICAGRELOR
-
A process for the preparation of a solid form of a compound of formula (VII) (Formula (VII)) comprises coupling(1R,2S)-2-(3,4-difluorophenyl)cyclopropanamine (R)-Mandelic acid of Formula (VI) with (2-[[(3a R,4S,6R,6aS)-6-[7-chloro-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-2,2- dimethyltetrahydro-3aH-cyclopenta[d[[1,3]dioxol-4-yl]oxy]-1-ethanol) of formula (V) in the presence of a suitable base and a first a suitable solvent at a suitable temperature to form 2- [[(3aR,4S,6R,6aS)-6-[7-[[(1R,2S)-2-(3,4-difluorophenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3- triazolo[4,5-d]pyrimidin-3-yl]-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]oxy]-1- ethanol of formula (VI)I; and isolating the compound of formula (VII) using a second suitable solvent so as to produce the compound of formula (VII) in solid form. A process for preparing Ticagrelor of formula (I) or a salt thereof (Formula (I)) comprises the conversion of a compound of formula (VII) in a solid form either as free base or as an acid addition salts thereof, into a compound of formula (I).
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Page/Page column 13; 14
(2016/03/22)
-
- AN IMPROVED PROCESS FOR PREPARATION OF TICAGRELOR AND INTERMEDIATES THEREOF
-
An improved, industrially viable, environment friendly and economically significant process for preparation of Ticagrelor is disclosed alongwith novel intermediates for the Ticagrelor synthesis.
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Page/Page column 13; 14
(2016/09/22)
-
- New ticagrelor preparation process
-
The present invention relates to a new ticagrelor preparation process, which comprises that 2-propylthio-4,6-dichloro-5-aminopyridine [intermediate I] and (1S,2R,3S,4R)-1-hydroxyethyl-2,3-O-isopropylidene-4-amino cyclopentane-1,2,3-triol tartrate [intermediate II] are subjected to condensation to obtain an intermediate 2-(((3R,4S,6R,6S)-6-((5-amino-6-chloro-2-(propylthio)pyrimidin-4-yl)amino)-2,2-dimethyl tetrahydro-4H-cyclopent[d][1,3]dioxo-4-yl)oxy)-1-ethanol [intermediate III], the intermediate III and trans-(1R,2S)-2-(3,4-difluorophenyl)cyclopropylamine [intermediate IV] are subjected to condensation to obtain 2-(((3aR,4S,6R,6aS)-6-((5-amino-6-(((1R,2S)-2-(3,4-difluorophenyl)cyclopropyl)amino)2-(propylthio)pyrimidin-4-yl)amino)-2,2-dimethyl tetrahydro-4H-cyclopentyl[d][1,3]dioxa-4-yl)oxy)-1-ethanol [intermediate V], the intermediate V is subjected to cyclization to obtain 2-(((3aR,4S,6R,6aS)-6-(7-(((1R,2S)-2-(3,4-difluorophenyl)cyclopropane)amino)-5-(propylthio)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-2,2-dimethyl tetrahydro-4H-cyclopentane[d][1,3]dioxa-4-yl)oxy)-1-ethanol [intermediate VI], and the intermediate VI is subjected to acetonylidene protection group removal to obtain the ticagrelor.
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Paragraph 0015
(2016/11/07)
-
- Synthesis method for ticagrelor
-
The invention discloses a synthesis method for ticagrelor.The synthesis method includes the following steps that 1, a compound I and a compound II are subjected to a coupling reaction under alkali existence, and then a compound III is obtained through extraction and recrystallization; 2, the compound III is subjected to a diazo reaction, extraction and washing, and a compound IV is obtained; 3, the compound IV is coupled with a compound V under the alkaline condition, and a compound VI is obtained through extraction, washing and concentration; 4, the compound VI is subjected to a deprotection reaction under the acid condition, and a compound VII, namely, ticagrelor is obtained through extraction and recrystallization.A solvent selected in the preparation method is free of toxins and environmentally friendly, the impurity removal process is simple, cost is low, and the yield and purity of the obtained product are both high.
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Paragraph 0028
(2016/10/17)
-
- PREPARATION OF TICAGRELOR
-
Provided are processes for preparing Ticagrelor and its intermediates that are useful in the processes. Also provided are salts of Ticagrelor, their processes and solid dispersion of Ticagrelor having Ticagrelor in amorphous form.
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Paragraph 0198
(2015/03/16)
-
- A PRODUCTION METHOD AND A NEW CRYSTALLINE FORM OF AN INTERMEDIATE OF SYNTHESIS OF TICAGRELOR
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The invention relates to preparation of ticagrelor of formula I and comprises a reaction of a compound of formula IV with a deprotection agent in a solvent to a compound of formula V, which is advantageously isolated by crystallization and subsequently used for the preparation of ticagrelor. The substituent R in formulae IV and V is CH2CH2OH, CH2COOH, or CH2COOR1; R1 is a branched or unbranched R1-C4 alkyl; and X is NH2, NO2f or NHCHO.
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Page/Page column 9; 10; 11
(2015/05/26)
-
- A PROCESS FOR PREPARATION OF TICAGRELOR AND INTERMEDIATES THEREOF
-
An improved process for the preparation of ticagrelor and its intermediates thereof; wherein the said process substantially eliminates the potential impurities.
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Page/Page column 80-81
(2014/07/21)
-
- Synthesis and biological evaluation of ticagrelor derivatives as novel antiplatelet agents
-
Ticagrelor (1) is the first reversible P2Y12 receptor antagonist blocking adenine diphosphate (ADP)-induced platelet aggregation with rapid onset and offset of effects. In this study, synthesis of ticagrelor and its derivatives has been accomplished in a convergent way. The compound design was based on modifications of ticagrelor and its major metabolite (33) in order to ameliorate their pharmacokinetic properties and dosing profile. The final compounds (1a-g, 35a-g) were evaluated for their inhibitory effect on ADP-induced platelet aggregation in rats. The assay results showed that some compounds (e.g., 1b, 1d, 33, 35b, 35f) exhibited comparable potency with that of ticagrelor.
- Zhang, Hao,Liu, Jun,Zhang, Luyong,Kong, Lingyi,Yao, Hequan,Sun, Hongbin
-
p. 3598 - 3602
(2012/07/14)
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- OPTICALLY ACTIVE SALTS OF (3AR,4S,6R,6AS)-6-AMINO-2,2-DIMETHYLTETRAHYDRO-3AH- CYCLOPENTA-[D] [1,3]DIOXOL-4-OL AND A METHOD OF THEIR PREPARATION
-
Diastereomeric salts of the compound of formula I with D-(-)-mandelic and R-(-)-3- chloromandelic acid, a method of for the preparation thereof and their use in the synthesis of the drug ticagrelor.
- -
-
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- CYCLOPROPYL MODULATORS OF P2Y12 RECEPTOR
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The present invention relates to new cyclopropyl modulators of P2Y12 receptor activity, pharmaceutical compositions thereof, and methods of use thereof.
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Page/Page column 41-42
(2011/02/24)
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- A PROCESS FOR PREPARING [1S- [1-ALPHA, 2-ALPHA, 3-BETA (1S*, 2R*) 5-BETA] ] -3- [7- [2- (3, 4-DIF LUOROPHENYL) -CYCLOPROPYLAMINO] - 5- (PROPYLTHIO) -3H-1, 2, 3-TRIAZOLO [4, 5-D] PYRIMIDIN-3-YL] -5- (2- HYDROXYETHOXY) CYCLOPENTANE-1, 2-DIOL AND TO ITS INTERMEDIATES
-
The present invention is directed to a process for preparing [1S-[1α,2α,3β(1S*,2R*),5β]]- 3-[7-[2-(3,4-difluorophenyl)-cyclopropylamino]-5-(propylthio)-3H-1,2,3-triazolo[4,5- d]pyrimidin-3-yl]-5-(2-hydroxyethoxy)cyclopentane-l,2-diol and to intermediates useful in the process.
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Page/Page column 7-8
(2010/04/06)
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- From ATP to AZD6140: The discovery of an orally active reversible P2Y12 receptor antagonist for the prevention of thrombosis
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Starting from adenosine triphosphate (ATP), the identification of a novel series of P2Y12 receptor antagonists and exploitation of their SAR is described. Modifications of the acidic side chain and the purine core and investigation of hydrophobic substituents led to a series of neutral molecules. The leading compound, 17 (AZD6140), is currently in a large phase III clinical trial for the treatment of acute coronary syndromes and prevention of thromboembolic clinical sequelae.
- Springthorpe, Brian,Bailey, Andrew,Barton, Patrick,Birkinshaw, Timothy N.,Bonnert, Roger V.,Brown, Roger C.,Chapman, David,Dixon, John,Guile, Simon D.,Humphries, Robert G.,Hunt, Simon F.,Ince, Francis,Ingall, Anthony H.,Kirk, Ian P.,Leeson, Paul D.,Leff, Paul,Lewis, Richard J.,Martin, Barrie P.,McGinnity, Dermot F.,Mortimore, Michael P.,Paine, Stuart W.,Pairaudeau, Garry,Patel, Anil,Rigby, Aaron J.,Riley, Robert J.,Teobald, Barry J.,Tomlinson, Wendy,Webborn, Peter J.H.,Willis, Paul A.
-
p. 6013 - 6018
(2008/04/02)
-
- Novel triazolo pyrimidine compounds
-
The present invention relates to a pyrimidine compound (I) useful as a pharmaceutical intermediate, to a process for preparing said pyrimidine compound, to intermediates used in said process, and to the use of said pyrimidine compound in the preparation of pharmaceuticals.
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