- Synthesis process of alogliptin benzoate
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The invention discloses a synthesis process of alogliptin benzoate. The synthesis process comprises the following steps: 1, preparing an initial raw material 6-chlorouracil; 2, preparing 2-((6-chlorine-2, 4-dioxo-3, 4-dihydro-2H-pyrimidine-1-radical)methyl)cyanophenyl; 3, preparing 2-[(6-chlorine-3, 4-dihydro-3-methyl-2, 4-dioxo-1(2H)-pyrimidinyl)methyl]benzonitrile; 4, preparing alogliptin; 5, preparing alogliptin benzoate. According to the invention, the alogliptin benzoate is synthesized by taking cheap and easily available 6-chlorouracil, alpha bromo-o-methylbenzonitrile and (R)-3-aminopiperidine as raw materials through reactions such as alkylation, methylation, affinity substitution, salification and the like; according to the synthetic route, raw materials are cheap and easy to obtain, the synthetic cost is reduced, all steps are classic reactions, and synthesis improvement is easy; the improved process is low in raw material cost, simple to operate, mild in reaction condition,simple in post-treatment and suitable for industrial production.
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Paragraph 0007; 0090; 0097-0119
(2021/02/10)
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- Identification and structure–activity relationship exploration of uracil-based benzoic acid and ester derivatives as novel dipeptidyl Peptidase-4 inhibitors for the treatment of type 2 diabetes mellitus
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Our previously reported carboxyl-containing DPP-4 inhibitors were highly potent but were poorly bioavailable. Esters of the carboxyl analogs exhibited a significant DPP-4 potency loss albeit with enhanced oral absorption. Herein, we described identificati
- Deng, Xiaoyan,Jiang, Neng,Jiang, Weizhe,Li, Qing,Meng, Liuwei,Xing, Junhao,Xu, Yanjun
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- A preparation method of the midbody [...] (by machine translation)
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The invention discloses a method of preparing intermediates of [...], including: will be 10.0 g raw material compound 1 is added to the 100 ml volume ratio of 1:1 of in the mixed solvent of DMSO/DMF, stirred at room temperature, after dissolving, adding 2
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Paragraph 0027-0032
(2018/12/02)
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- PROCESS FOR PREPARATION OF ALOGLIPTIN
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Provided is a novel process for the preparation of alogliptin.
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Paragraph 0129
(2016/12/12)
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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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- NOVEL SALTS OF ALOGLIPTIN
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The present invention provides a novel process for the preparation of amorphous alogliptin benzoate. The present invention also provides amorphous alogliptin benzoate co-precipitated on copovidone, process for its preparation and pharmaceutical compositions comprising it. The present invention further provides novel salts of alogliptin, processes for their preparation and pharmaceutical compositions comprising them. The present invention further provides crystalline hydrochloride salt of alogliptin, process for its preparation and pharmaceutical compositions comprising it. The present invention further provides crystalline tartrate salt of alogliptin, process for its preparation and pharmaceutical compositions comprising it.
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Page/Page column 19
(2013/04/13)
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- Design and synthesis of pyrimidinone and pyrimidinedione inhibitors of dipeptidyl peptidase IV
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The discovery of two classes of heterocyclic dipeptidyl peptidase IV (DPP-4) inhibitors, pyrimidinones and pyrimidinediones, is described. After a single oral dose, these potent, selective, and noncovalent inhibitors provide sustained reduction of plasma DPP-4 activity and lowering of blood glucose in animal models of diabetes. Compounds 13a, 27b, and 27j were selected for development.
- Zhang, Zhiyuan,Wallace, Michael B.,Feng, Jun,Stafford, Jeffrey A.,Skene, Robert J.,Shi, Lihong,Lee, Bumsup,Aertgeerts, Kathleen,Jennings, Andy,Xu, Rongda,Kassel, Daniel B.,Kaldor, Stephen W.,Navre, Marc,Webb, David R.,Gwaltney, Stephen L.
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experimental part
p. 510 - 524
(2011/03/20)
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- Synthesis of a novel analogue of DPP-4 inhibitor Alogliptin: Introduction of a spirocyclic moiety on the piperidine ring
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We report the synthesis of a novel analogue of Alogliptin via condensation of two key intermediates one of which is an aminopiperidine derivative bearing a spirocyclic ring on the piperidine moiety. Preparation of the aminopiperidine intermediate was carried out by constructing the cyclopropyl ring prior to assembling the piperidine ring.
- Kodimuthali, Arumugam,Pal, Manojit,Prasunamba, Padala Lakshmi
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supporting information; experimental part
(2010/11/21)
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- DIPEPTIDYL PEPTIDASE INHIBITORS
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Methods of making compounds of the formula (I) wherein the variables are as defined herein. Also, methods of making compounds that may be used to inhibit dipeptidyl peptidase.
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Page/Page column 22
(2009/12/02)
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- POLYMORPHS OF BENZOATE SALT OF 2-[[6-[(3R)-3-AMINO-1-PIPERIDINYL]-3,4-DIHYDRO-3-METHYL-2,4-DIOXO-1(2H)-PYRIMIDINYL]METHYL]-BENZONITRILE AND METHODS OF USE THEREFOR
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Compositions comprising Compound I, wherein the Compound I is present in one or more polymorphic forms. Also provided are kits and articles of manufacture with compositions comprising one or more polymorphs of Compound I, and methods of using the compositions to treat various diseases.
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Page/Page column 13; 14
(2008/06/13)
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- Discovery of alogliptin: A potent, selective, bioavailable, and efficacious inhibitor of dipeptidyl peptidase IV
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Alogliptin is a potent, selective inhibitor of the serine protease dipeptidyl peptidase IV (DPP-4). Herein, we describe the structure-based design and optimization of alogliptin and related quinazolinone-based DPP-4 inhibitors. Following an oral dose, these noncovalent inhibitors provide sustained reduction of plasma DPP-4 activity and a lowering of blood glucose in animal models of diabetes. Alogliptin is currently undergoing phase 111 trials in patients with type 2 diabetes.
- Feng, Jun,Zhang, Zhiyuan,Wallace, Michael B.,Stafford, Jeffrey A.,Kaldor, Stephen W.,Kassel, Daniel B.,Navre, Marc,Shi, Lihong,Skene, Robert J.,Asakawa, Tomoko,Takeuchi, Koji,Xu, Rongda,Webb, David R.,Gwaltney II, Stephen L.
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p. 2297 - 2300
(2008/02/05)
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- Dipeptidyl peptidase inhibitors
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Compounds, pharmaceuticals, kits and methods are provided for use with DPP-IV and other S9 proteases that comprise a compound comprising Formula I: wherein M is N or CR4; Q1 and Q2 are each independently selected from the group consisting of CO, SO, SO2, and C=NR9; and each R1, R2, R3, R4 and R9 are as defined herein.
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Page/Page column 43
(2008/06/13)
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