- Design and synthesis of purine connected piperazine derivatives as novel inhibitors of Mycobacterium tuberculosis
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A series of novel purine linked piperazine derivatives were synthesized to identify new, potent inhibitors of Mycobacterium tuberculosis. The compounds were designed to target MurB disrupting the biosynthesis of the peptidoglycan and exert antiproliferative effects. The first series of purine-2,6-dione linked piperazine derivatives were synthesized using an advanced intermediate 1-(3,4-difluorobenzyl)-7-(but-2-ynyl)-3-methyl-8-(piperazin-1-yl)-1H-purine-2,6(3H,7H)-dione hydrochloride (6) which was coupled with varied carboxylic acid chloride derivatives. Following this piperazine linked derivatives were also synthesized from 6 using diverse isocyanate partners. The anti-mycobacterial activity of the analogues was tested against Mycobacterium tuberculosis H37Rv which revealed a cluster of six analogues (11, 24, 27, 32, 33 and 34), possessed promising activity. In comparison, a set of these new compounds possessed greater potencies relative to current drugs used in the clinic such as Ethambutol. These results were also correlated with computational molecular docking analysis, providing models for strong interactions of the inhibitors with MurB providing a template for the future development of preclinical agents against Mycobacterium tuberculosis.
- Konduri, Srihari,Prashanth, Jyothi,Krishna, Vagolu Siva,Sriram, Dharmarajan,Behera,Siegel, Dionicio,Rao, Koya Prabhakara
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- Design, synthesis and biological evaluation of novel 1,2,3-triazole-based xanthine derivatives as DPP-4 inhibitors
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Abstract: Inhibitors of dipeptidyl peptidase-4 (DPP4) have been shown to be effective treatments for type 2 diabetes. A series of novel 1,2,3-triazole based xanthine derivatives were designed and evaluated for in vitro dipeptidyl peptidase-4 (DPP-4) activity. Among them, the representative compounds 7b, 7e, 7g and 6e showed excellent inhibitory activity of DPP-4 with IC50 values ranging from 87.41 to 16.34 nM, respectively. The SAR of these xanthine derivatives have been discussed, which would be useful for developing novel DPP-4 inhibitors as treating type 2 diabetes. Graphic Abstract: 1,2,3-triazole based xanthine derivatives were designed and evaluated for in vitro dipeptidyl peptidase-4 (DPP-4) activity. The SAR of these xanthine derivatives had been discussed, which would be useful for developing novel DPP-4 inhibitors as treating type 2 diabetes.[Figure not available: see fulltext.].
- Battula, Kumara Swamy,Nagavelli, Vasudeva Reddy,Narsimha, Sirassu,Ravinder, M.,Reddy, Y. N.
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Read Online
- Preparation method of hypoglycemic drug linagliptin intermediate
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The invention provides a preparation method of a hypoglycemic drug linagliptin intermediate, wherein the method comprises the steps: in the presence of a catalyst and an organic solvent, carrying out condensation reaction on o-aminoacetophenone (1) and 2-chloroacetamide (2) to obtain an intermediate II; carrying out condensation, bromination, substitution and other reactions on 4-(methylamino)-1H-imidazol-5-carboxamide (3) to generate an intermediate III; and finally, carrying out alkylation reaction on the intermediate II and the intermediate III to generate an intermediate I. According to the preparation method, generation of side reactions are avoided. Moreover, the reaction cost is saved, the operation conditions are mild, the yield is high, the post-treatment is simple, and the method is suitable for industrial large-scale production.
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- Novel preparation process of linagliptin
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The invention discloses a novel preparation process of linagliptin. 8-bromo-3-methyl xanthine (SM1) is used as an initial raw material, DMF is used as a solvent and reacts with 1-bromo-2-butyne (SM2)under the alkaline condition to obtain an intermediate I, then the intermediate I reacts with 2-chloromethyl-4-methyl quinazol (SM3) under the solvent system to obtain an intermediate II, the intermediate II and (R) 3-aminopiperidine dihydrochloride (SM4) are subjected to a substitution reaction, and finally anti-type 2 diabetes drug linagliptin (I) is prepared. By adopting a one-pot method, the method has the advantages that the raw material cost is low, the yield is high, the post-treatment operation of each step of chemical reaction in multi-step reaction is reduced, the production period is greatly shortened, few impurities are generated in the reaction, the product quality is high, the use amount of chemical reagents is relatively reduced, and the method is relatively green and environment-friendly, and is beneficial to industrial production.
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Paragraph 0043-0045; 0050-0055
(2021/01/24)
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- Novel preparation process of linagliptin
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The invention discloses a novel preparation process of linagliptin. 8-bromine-3-methyl xanthine (SM1) is used as an initial raw material, DMF is used as a solvent to react with 1-bromine-2-butyne (SM2) under an alkaline condition to obtain an intermediate I, then the intermediate I reacts with 2-chloromethyl-4-methyl quinazol (SM3) under the solvent system to obtain an intermediate II, and the solvent system reacts with (R)-3-Boc-aminopiperidine (SM4) under the alkaline condition to obtain an intermediate III; and the protecting group is dissociated by using acid to obtain the linagliptin (I) for resisting type 2 diabetes mellitus. By adopting a one-pot method, the method has the advantages that the raw material cost is low, the yield is high, the post-treatment operation of each step of chemical reaction in multi-step reaction is reduced, the production period is greatly shortened, few impurities are generated in the reaction, the product quality is high, the use amount of chemical reagents is relatively reduced, and the method is relatively green and environment-friendly, and is beneficial to industrial production.
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Paragraph 0041-0043
(2021/05/01)
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- Linagliptin intermediate compound V
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The invention belongs to the field of pharmaceutical chemicals, and provides a linagliptin intermediate compound V and an important intermediate for synthesizing linagliptin by using the intermediateV. The method solves the problems of self-coupling of linagliptin intermediates and generation of large impurities in the prior art, and the synthesized novel intermediate compound V has the advantages of high yield, simple operation, significantly reduced production cost, and suitableness for industrial production.
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- Linagliptin intermediate compound IV
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The invention belongs to the field of pharmaceutical chemicals, and discloses a linagliptin intermediate IV and a novel route for synthesizing an important linagliptin intermediate from the linagliptin intermediate IV. The linagliptin intermediate IV synthesized in the invention has the advantages of high yield, simple operation, substantial reduction of production cost, suitableness for industrial production; and the synthesis route solves the problems of self-coupling of linagliptin intermediates and generation of large impurities in the prior art.
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- Preparation method of linagliptin intermediate
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The invention provides a preparation method of a linagliptin intermediate. The preparation method comprises the following steps: (1) reacting 2-bromo-4-methylimidazole, N-methylurea and an oxidizing agent to obtain a compound II; (2) reacting the compound II with a bromine source in the presence of an alkali to obtain a compound III; and (3) reacting the compound III with 1-bromo-2-butyne in the presence of alkali to obtain a compound IV that is the key linagliptin intermediate. The method has the advantages of cheap and easily available initial raw materials, simplified steps, high atom utilization rate, mild reaction conditions, high yield, suitability for industrial production and the like.
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Paragraph 0052-0058
(2019/12/25)
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- Rapid generation of novel benzoic acid–based xanthine derivatives as highly potent, selective and long acting DPP-4 inhibitors: Scaffold-hopping and prodrug study
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A series of novel xanthine derivatives 2a-l incorporating benzoic acid moieties were rapidly generated by using strategy of scaffold-hopping from our previously reported scaffold uracil to xanthine, a scaffold of approved drug linagliptin. After systematic structure-activity relationship (SAR) study around benzoic acid moieties, 5 novel DPP-4 inhibitors with low picomolar potency range (IC50 50 value of 0.1 nM for DPP-4, showed 22-fold improvement in inhibitory activity compared to lead compound uracil 1, its activity was 45-fold more potent than alogliptin. 2e, 2f, 2i and 2k were selected for pharmacokinetic evaluation, and 2f and 2i showed the better pharmacokinetic profiles after iv administration, but poor oral bioavailability. To improve the oral pharmacokinetic profile, prodrug design approach was performed around 2f and 2i. Esters of 2f and 2i were synthesized and evaluated for stability, toxicity and pharmacokinetics. Compound 3e, the methyl ester of compound 2f, was identified to demonstrate good stability, low toxicity and improved oral bioavailability, with 3-fold higher blood concentration compared to 2f in rats. The following in vivo evaluations revealed 3e provided a sustained pharmacodynamics effect for 48h, and robustly improved glucose tolerance in normal ICR and db/db mice in dose-dependent manner. Chronic treatments investigations demonstrated that 3e achieved more beneficial effects on fasting blood glucose levels and glucose tolerance than alogliptin in type 2 diabetic db/db mice. The overall results have shown that compound 3e has the potential to efficacious, safety and long-acting treatment for T2DM.
- Li, Qing,Meng, Liuwei,Zhou, Siru,Deng, Xiaoyan,Wang, Na,Ji, Yi,Peng, Yichun,Xing, Junhao,Yao, Gongmei
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p. 509 - 523
(2019/07/25)
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- Substituted xanthine compound and its preparation and use (by machine translation)
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The invention discloses substituted xanthine compounds, a preparation method and applications thereof, and specifically relates to compounds represented by the formula (I), stereo isomers and pharmaceutically acceptable salts thereof, wherein the R1 and R2 are defined in the description. The invention also relates to a pharmaceutical composition containing the compounds, an application of the pharmaceutical composition in preparation of drugs for treating diseases or symptoms caused by high activity of DPP-IV or overexpression of DPP-IV, and a method using the pharmaceutical composition to treat related diseases. The provided compounds can effectively inhibit the activity of DPP-IV.
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- Xanthine compound and pharmaceutical composition and application thereof
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The invention discloses a xanthine derivative as shown in the formula (I) and a pharmaceutical composition and application thereof. The xanthine derivative is prepared from a compound as shown in theformula (I) or a stereoisomer, a geometrical isomer, a hydrate or a solvate thereof, or a pharmaceutically acceptable salt or prodrug as shown in the description. The invention also relates to application of the compound as shown in the formula (I) and the pharmaceutical composition thereof as a DPP-4 inhibitor, and especially application in preparation of medicines for treating and/or preventingmetabolic disorder diseases such as diabetes.
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- XANTHINE DERIVATIVE
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The present invention relates to a Xanthine derivative as shown in formula (I), wherein, R is selected from: R1 is selected from cyano or methoxycarbonyl; R2 is selected from hydrogen and halogen atoms, a linear or branched C1-6 alkyl group which is substituted or unsubstituted by 1 to 5 halogen atoms, a linear or branched C1-6 alkoxy group which is substituted or unsubstituted by 1 to 5 halogen atoms; X and Y are each independently selected from C or N; and n is 0, 1, 2, 3 or 4.
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Page/Page column 0025; 0026; 0027
(2018/04/19)
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- Xanthine derivatives
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The invention discloses xanthine derivatives and isomers. Through normal mice sugar tolerance influence tests and beagle dog in-vivo DPP-IV activity inhibition tests, the compounds show excellent DPP-IV inhibition activity, and are applicable to prepare medicines for treating diseases correlated to dipeptidyl peptidase IV.
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Paragraph 0052-0054
(2017/04/12)
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- A method for preparing advantage Geleg sandbank (by machine translation)
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The invention discloses a method for preparing advantage Geleg sandbank, comprising the following steps: the tert-butoxy-carbonyl-Leigh geleg sandbank (g) is added to the methanol aqueous solution, the stirring is then started, in an inert atmosphere and heating to reflux of the reaction is carried out under the state, get advantage Geleg sandbank, wherein the reaction temperature is 25-50°C, the reaction time is 3-12h, tert-butoxy-carbonyl-Leigh geleg sandbank (g) with the weight proportion of the methanol water solution 100 : (400-550). Method for preparing advantage Geleg sandbank of this invention, is under the protection of inert gas and methanol aqueous solution Boc protecting group on the method, no longer need expensive trifluoro acetate-DCM Boc protecting group on the reaction, only use the cheap methanol-water systems can be, and after treatment is simple, and three suitable the reaction of acid-DCM system, generating a plurality of impurities, the after-treatment and purification process is extremely tedious. Furthermore, it is also possible to avoid the use of the strong acid intermediate (g) and row Gurley sandbank impurity such as in the breaking of amide linkage. (by machine translation)
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Paragraph 0097;0098
(2016/10/31)
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- Polymorphs of a xanthine compound and its preparation method, use
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The invention relates to the field of pharmaceutical chemistry synthesis, and concretely relates to multiple crystal forms of 1-[(5-fluoro-1,3-benzothiazol-2-yl)]-3-methyl-7-(2-but-1-ynyl)-8-[(R)-3-aminopiperidin-1-yl]-xanthine compound, a preparation method thereof, and application thereof as a treatment medicine, especially as a dipeptidyl peptidase IV (DPP-IV) inhibitor.
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Paragraph 0057-0058; 0089-0092
(2017/02/09)
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- Xanthine derivatives (by machine translation)
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The invention discloses a type of xanthine derivatives and isomers. Through tests about influences on normal mice sugar tolerance and in-vitro DPP-IV activity inhibiting tests, the compounds provided by the invention show excellent DPP-IV inhibiting activity, and can be used for preparation of medicines treating diseases related to dipeptidyl peptidase IV.
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Paragraph 0059; 0061; 0062; 0063
(2016/11/24)
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- Xanthine derivatives
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The invention discloses xanthine derivatives and isomers. Through normal mice sugar tolerance influence tests and beagle dog in-vivo DPP-IV activity inhibition tests, the compounds show excellent DPP-IV inhibition activity, and are applicable to prepare medicines for treating diseases correlated to dipeptidyl peptidase IV.
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Paragraph 0052; 0053; 0054
(2017/02/28)
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- Xanthine derivatives, their preparation and use
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The present invention relates to a xanthine derivative, a pharmaceutically acceptable salt thereof, a solvate of the derivative, a solvate of the pharmaceutically acceptable salt, a chemically protected form or prodrug thereof and a preparation method and a use thereof; and also relates to an intermediate compound used for preparing the xanthine derivative and a preparation method of the intermediate compound. The xanthine derivative and a pharmaceutical composition thereof effectively inhibit the activity of DPP-IV, and can be used for preparing a drug for diseases associated with dipeptidyl peptidase (DPP-IV).
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Paragraph 0146-0148
(2017/02/28)
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- A method for synthesizing advantage Geleg sandbank (by machine translation)
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The invention discloses a method for synthesizing advantage Geleg sandbank, comprising the following steps : (1) the 8- [...] the 3 [...] methyl xanthine (a) and the 1 [...] -2 the butyne [...] (b) reaction, from the 3 [...] methyl -7 the [...] (2 the [...] butyne-l-yl) - 8 the [...] bromo-xanthine (c) ; (2) the 3 [...] methyl -7 the [...] (2 the [...] butyne-l-yl) - 8 the [...] bromo-xanthine (c) and 2 the [...] methyl -4 the methyl [...] quinazoline (d) reaction, to obtain the 1 [...] [(4 the [...] methyl quinazoline -2 the [...] ) methyl] - 3 the [...] methyl -7 the [...] (2 the [...] butyne -1 the [...] yl) - 8 the xanthine [...] (e) ; (3) to the 1 [...] [(4 the [...] methyl quinazoline -2 the [...] ) methyl] - 3 the [...] methyl -7 the [...] (2 the [...] butyne -1 the [...] yl) - 8 the xanthine [...] (e), (R) - 3 the ??Boc-amino piperidine (f), the potassium carbonate and acetonitrile added into the reactor, and they are uniformly mixed, under the state of the heating under reflux for reaction, the tert-butoxy-carbonyl-Leigh geleg sandbank (g) ; (4) the tert-butoxy-carbonyl-Leigh geleg sandbank (g) removing the protecting group Boc in aqueous solution of methanol, to obtain advantage Geleg sandbank. The synthetic method of this invention has no environmental pollution, high yield, no impurities. (by machine translation)
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Paragraph 0116; 0117
(2017/01/17)
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- A as dipeptidyl peptidase -4 inhibitor for the preparation of compounds of the
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The invention relates to a preparation method of a biguanide derivative as a dipeptidyl peptidase-4 inhibitor (DPP-IV). The biguanide derivative can be used for treating all symptoms or diseases benefited by inhibiting the activity of DPP-IV, for example type 1 and 2 diabetes, diabetic complication and other related diseases.
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Paragraph 0052-0054
(2016/10/08)
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- Intermediate for preparing compound as dipeptidyl peptidase-4 inhibitor
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The present invention relates to an intermediate for preparing a compound as a dipeptidyl peptidase-4 inhibitor. The biguanide derivative can be used for the treatment of all conditions or disorders benefiting from inhibition of DPP-IV activity, such as type I and type II diabetes, diabetic complications and other related diseases.
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Paragraph 0054; 0055; 0056; 0057; 0058; 0059; 0060
(2016/10/08)
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- A as dipeptidyl peptidase -4 inhibitor compounds
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The invention relates to a compound as a dipeptidyl peptidase-4 (DPP-IV) inhibitor, which can be used for treating all symptoms or diseases that get benefits by inhibiting DPP-IV activity, such as type I and II diabetes, diabetes complications and other related diseases.
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Paragraph 0061; 0062; 0063; 0064; 0065; 0066
(2016/10/08)
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- A preparation as dipeptidyl peptidase -4 inhibitors of the intermediate compounds
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The invention relates to an intermediate for preparing a compound as a dipeptidyl peptidase-4 inhibitor. Biguanide derivatives can be used for treating all symptoms or disorders benefiting due to inhibition of DPP-IV activity, such as type 1 diabetes and type 2 diabetes, diabetes complication and other related diseases.
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Paragraph 0055; 0056; 0057; 0058; 0059
(2016/10/09)
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- Linagliptin impurity, and preparation method and application thereof
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The invention discloses a linagliptin impurity as shown in a formula (I) which is described in the specification, a preparation method for the linagliptin impurity and application of the linagliptin impurity as an impurity reference substance for inspection of substance related to linagliptin. As the linagliptin impurity is applied as a standard reference substance, linagliptin quality can be effectively controlled, and security risks of a drug can be reduced, so security and validity of the linagliptin preparation in clinical application can be guaranteed.
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Paragraph 0026; 0027; 0028
(2016/10/10)
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- Simple preparation method of high-purity linagliptin
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The invention relates to a simple preparation method of high-purity linagliptin. The method includes the steps of making 8-bromine-3-methyl xanthine and 1-bromo-2-butyne react, directly adding 2-chloromethyl-4-methylquinazoline without processing after reaction is completed, preparing a key intermediate 8-bromine-7-(2-butyne-1-yl)-3,7-dihydro-3-methyl-1-[(4-methyl-2-quinazolinyl)methyl]-1H-purine-2,6-diketone of linagliptin through a one-pot method, making the intermediate react with (R)-3-piperidinamine dihydrochloride after being filtered and separated to obtain a linagliptin solution, and obtaining a linagliptin pure product after processing the linagliptin solution. The key intermediate is prepared through the one-pot method, operation is convenient, and yield is increased; the key intermediate reacts with (R)-3-piperidinamine dihydrochloride after being separated, and therefore high-purity linagliptin is obtained, and the requirements for production and declaration of pharmaceutical enterprises are met to the maximum extent.
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Paragraph 0029
(2016/11/17)
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- METHOD FOR PREPARING AN IMPORTANT INTERMEDIATE OF LINAGLIPTIN
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The present invention discloses an improved process for preparing an important intermediate of linagliptin. In particular, disclosed are a process for preparing a compound V which is an important intermediate of linagliptin and has the structure V, and an industrial process of preparing linagliptin having excellent chemical and optical purities, which is an inhibitor of dipeptidyl peptidase-4 (DPP-IV), from the compound V. The process employs a phase-transfer catalyst, is high in yield, easy and simple to handle, environmentally friendly, suitable for industrial mass production, and can be implemented by a “one-pot process”.
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Paragraph 0056-0060
(2015/12/20)
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- XANTHINE DERIVATIVE
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The present invention discloses a xanthine derivative having the structure of the following general formula (I) or a pharmaceutically acceptable salt thereof; further discloses a preparation method for the xanthine derivative or a pharmaceutically acceptable salt thereof; and further discloses the use of the xanthine derivative or a pharmaceutically acceptable salt thereof. Through experiments of DPP-IV activity inhibition experiments in vitro, impact on glucose tolerance in normal mice and impact on blood glucose in spontaneous diabetic mice, it proves that the compounds and pharmaceutically acceptable salts thereof show good DPP-IV inhibition activity, can be applied to prepare medicines for treating dipeptidyl peptidase IV-related diseases, and more particularly, can be applied to the use of medicines for treating type II diabetes or diseases of abnormal glucose tolerance.
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Paragraph 0035
(2015/05/06)
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- XANTHINE DERIVATIVE
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The present invention discloses a xanthine derivative having the structure of the following general formula (I) or a pharmaceutically acceptable salt thereof; further discloses a preparation method for the xanthine derivative or a pharmaceutically acceptable salt thereof; and further discloses the use of the xanthine derivative or a pharmaceutically acceptable salt thereof. Through experiments of DPP-IV activity inhibition experiments in vitro, impact on glucose tolerance in normal mice and impact on blood glucose in spontaneous diabetic mice, it proves that the compounds and pharmaceutically acceptable salts thereof show good DPP-IV inhibition activity, can be applied to prepare medicines for treating dipeptidyl peptidase IV-related diseases, and more particularly, can be applied to the use of medicines for treating type II diabetes or diseases of abnormal glucose tolerance.
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Paragraph 0047-0048
(2015/07/15)
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- AN IMPROVED PROCESS FOR THE PREPARATION OF LINAGLIPTIN
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The present invention relates to a process for preparing Linagliptin by purifying the intermediate compounds converting the purified intermediates into Linagliptin. The present invention also relates to the preparation of an amorphous Linagliptin.
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- Discovery of highly potent DPP-4 inhibitors by hybrid compound design based on linagliptin and alogliptin
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Highly potent DPP-4 inhibitors have been identified by hybrid compound design based on linagliptin and alogliptin. The most promising compound 2h (IC50 = 0.31 nM) exhibited 8.5-fold and 2.5-fold more potent activity than that of alogliptin (IC50 = 2.63 nM) and linagliptin (IC 50 = 0.77 nM), respectively. Compound 2h had a good inhibition selectivity for DPP-4 over DPP-8/9 and thus was selected for further biological evaluation, including oral glucose tolerance, plasma DPP-4 inhibitory activity, pharmacokinetic profile, acute toxicity and hERG inhibition. The assay results showed that 2h displayed significant in vivo glucose-lowering effect and low risk of toxicity. Further studies are expected to confirm 2h as a potential drug candidate for the treatment of type 2 diabetes.
- Lai, Zeng-Wei,Li, Chunhong,Liu, Jun,Kong, Lingyi,Wen, Xiaoan,Sun, Hongbin
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p. 547 - 560
(2014/07/21)
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- Selective inhibitors of fibroblast activation protein (FAP) with a xanthine scaffold
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Fibroblast activation protein (FAP) is a serine protease that is selectively expressed in many diseases involving activated stroma, including cancer, arthritis and hepatic and pulmonary fibrosis. FAP is closely related to dipeptidyl peptidase IV (DPPIV), of which many inhibitors are known and several are marketed as drugs. One of these is the xanthine derivative linagliptin. In a broad literature screen amongst reported DPPIV inhibitors, linagliptin was the only druglike compound identified that possessed significant FAP potency. Hence, this compound served as a starting point for a SAR study that aimed to identify structural determinants that selectively increase FAP-potency of linagliptin analogues. By investigating the influence of the substitution pattern on N1, N7 and C8 of the xanthine scaffold, we managed to decouple DPPIV and FAP potency and identified the first selective xanthine-based FAP inhibitors with low micromolar potency. Furthermore, these compounds are the only known FAP-inhibitors that do not rely on a warhead functionality to obtain potencies in this range.
- Jansen, Koen,De Winter, Hans,Heirbaut, Leen,Cheng, Jonathan D.,Joossens, Jurgen,Lambeir, Anne-Marie,De Meester, Ingrid,Augustyns, Koen,Van Der Veken, Pieter
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p. 1700 - 1707
(2014/12/12)
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- IMPROVED PROCESS FOR PREPARATION OF PURE LINAGLIPTIN
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The present application provides a process for preparation of Linagliptin reacting (R)-piperidine-3-amine of Formula II or an acid addition salt thereof with 1-[(4-methyl- quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-bromoxanthine of Formula III in the presence of a suitable base in an inert organic solvent.
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Page/Page column 11
(2013/07/19)
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- SOLID STATE FORMS OF LINAGLIPTIN
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The present invention provides solid state forms of Linagliptin, processes for preparing the solid state forms, and pharmaceutical compositions thereof.
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Paragraph 0181
(2013/05/22)
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- 8-(3-(R)-aminopiperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin- 2-ylmethyl)-3,7-dihydropurine-2,6-dione (BI 1356), a highly potent, selective, long-acting, and orally bioavailable DPP-4 inhibitor for the treatment of type 2 diabetes
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A new chemical class of potent DPP-4 inhibitors structurally derived from the xanthine scaffold for the treatment of type 2 diabetes has been discovered and evaluated. Systematic structural variations have led to 1 (BI 1356), a highly potent, selective, long-acting, and orally active DPP-4 inhibitor that shows considerable blood glucose lowering in different animal species. 1 is currently undergoing clinical phase IIb trials and holds the potential for once-daily treatment of type 2 diabetics.
- Eckhardt, Matthias,Langkopf, Elke,Mark, Michael,Tadayyon, Moh,Thomas, Leo,Nar, Herbert,Pfrengle, Waldemar,Guth, Brian,Lotz, Ralf,Sieger, Peter,Fuchs, Holger,Himmelsbach, Frank
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p. 6450 - 6453
(2008/04/12)
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- NOVEL 8-(PIPERAZINE-1-YL)- AND 8-([1,4]DIAZEPAN-1-YL)-XANTHINE, THE PRODUCTION AND USE THEREOF IN THE FROM OF A DRUG
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The invention relates to a substituted XANTHINE of formula (I), wherein R1 to R3 and n are such as defined in claims from 1 to 8 and tautomers, enantiomers, diastereomers, mixtures, prodrugs and the salts thereof, said substances exhibiting valuable pharmacological properties, in particular an inhibition on the activity of dipeptidylpeptidasa-IV enzyme (DPP-IV).
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Page/Page column 19
(2008/06/13)
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- 8-[3-AMINO-PIPERIDIN-1-YL]-XANTHINE, THE PRODUCTION THEREOF AND THE USE IN THE FORM OF A DPP INHIBITOR
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The invention relates to substituted xanthines of general formula (I), wherein R is such as defined in claim 1, and to the tautomers, stereoisomers, mixtures and the salts thereof, said products exhibiting precious pharmacological properties, in particular an inhibiting effect on a dipeptidylpeptidasa-IV (DPP-IV) enzyme activity.
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Page/Page column 32
(2008/06/13)
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- 8-[3-amino-piperidin-1-yl]-xanthines, their preparation and their use as pharmaceutical compositions
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The present invention relates to substituted xanthines of general formula wherein R is defined as in claim 1, the tautomers, the stereoisomers, the mixtures thereof and the salts thereof, which have valuable pharmacological properties, particularly an inhibiting effect on the activity of the enzyme dipeptidylpeptidase-IV (DPP-IV).
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Page/Page column 9
(2008/06/13)
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- Bicyclic imidazole derivatives, the preparation thereof and their use as pharmaceutical compositions
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The present invention relates to bicyclic imidazole compounds of general formula wherein R1 to R3 and A are defined as in claims 1 to 8, the tautomers, the enantiomers, the stereoisomers, the mixtures thereof and the salts thereof, which have valuable pharmacological properties, particularly an inhibiting effect on the activity of the enzyme dipeptidylpeptidase-IV (DPP-IV).
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Page/Page column 7
(2010/02/12)
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- NOVEL XANTHINE DERIVATIVES, THE PRODUCTION AND THE USE THEREOF IN THE FORM OF DRUGS
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The invention relates to xanthines presented by a general formula (I), wherein R1 to R4 are equal to these defined in the claim n° 1, and to tautomers, stereoisomers, mixtures, pro-drugs and the salts thereof. Said compounds exhibit advantages pharmacological properties, in particular an inhibiting action on the activity of enzyme dipeptidylpeptidasa-IV (DPP-IV).
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Page/Page column 49
(2008/06/13)
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- XANTHINE DERIVATIVES, PRODUCTION THEREOF AND USE THEREOF AS MEDICINES
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The invention concerns substituted xanthines of general formula (I), wherein: R1 to R4 are such as defined in Claim 1, and tautomers, stereoisomers, mixtures, prodrugs and salts thereof. Said compounds have advantageous pharmacological properties, in particular an inhibiting effect on the activity of the dipeptidyl peptidase IV (DPP-IV) enzyme.
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Page/Page column 34
(2008/06/13)
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- NOVEL XANTHIN DERIVATIVES, PRODUCTION AND USE THEREOF AS MEDICAMENTS
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The invention relates to substituted xanthins of general formula (I) wherein R1 - R4 are defined as in Claim 1, the tautomers thereof, the stereoisomers thereof, the mixtures thereof, the prodrugs and salts thereof which exhibit valuable pharmacological properties, especially an inhibitive effect on the activity of the enzyme Dipeptidylpeptidase-IV (DPP-IV).
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Page/Page column 40
(2008/06/13)
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