- Preparation method of pazopanib intermediate
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The invention provides a preparation method of a pazopanib key intermediate 2,3-dimethyl-N-(2-chloropyrimidin-4-yl)-N-methyl-2H-indazole-6-amine. The method comprises the following steps: by taking 6-halogenated-2,3-dimethyl-2H-indazole as a raw material, conducting reacting to obtain N,2,3-trimethyl-2H-indazole-6-amine; and further carrying out a reaction to obtain the 2,3-dimethyl-N-(2-chloropyrimidin-4-yl)-N-methyl-2H-indazole-6-amine. The method has the advantages of short synthesis route, accessible raw materials, low cost, mild reaction conditions, high safety and high yield, and is suitable for industrial mass production.
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- High Turnover Pd/C Catalyst for Nitro Group Reductions in Water. One-Pot Sequences and Syntheses of Pharmaceutical Intermediates
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Commercially available Pd/C can be used as a catalyst for nitro group reductions with only 0.4 mol % Pd loading. The reaction can be performed using either silane as a transfer hydrogenating agent or simply a hydrogen balloon (μ1 atm pressure). With this technology, a series of nitro compounds was reduced to the desired amines in high chemical yields. Both the catalyst and surfactant were recycled several times without loss of reactivity.
- Gallou, Fabrice,Li, Xiaohan,Lipshutz, Bruce H.,Takale, Balaram S.,Thakore, Ruchita R.
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supporting information
p. 8114 - 8118
(2021/10/25)
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- Design, synthesis and bioevaluation of novel 6-substituted aminoindazole derivatives as anticancer agents
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In the present study, a series of 6-substituted aminoindazole derivatives were designed, synthesized, and evaluated for bio-activities. The compounds were initially designed as indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors based on the structural feature of five IDO1 inhibitors, which are currently on clinical trials, and the important anticancer activity of the indazole scaffold. One of them, compound N-(4-fluorobenzyl)-1,3-dimethyl-1H-indazol-6-amine (36), exhibited a potent anti-proliferative activity with an IC50 value of 0.4 ± 0.3 μM in human colorectal cancer cells (HCT116). This compound also remarkably suppressed the IDO1 protein expression. In the cell-cycle studies, the suppressive activity of compound 36 in HCT116 cells was related to the G2/M cell cycle arrest. Altogether, the current findings demonstrate that compound 36 would be promising for further development as a potential anticancer agent.
- Anh, Le Viet,Hai, Dinh Thi Thanh,Han, Byung Woo,Hien, Tran Thi Thu,Hoang, Ngo Xuan,Hoang, Van-Hai,Long, Nguyen Huu,Luu, Hung N.,Luu, Thi-Thu-Trang,Ngo, Son Tung,Ngo, Thien,Nguyen, Thanh Xuan,Nguyen, Yen Thi Kim,Tran, Phuong-Thao,Van Hieu, Duong
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p. 45199 - 45206
(2020/12/30)
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- Method for synthesizing 2,3-dimethyl-6-amino-2H-indazole by microchannel hydrogenation
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The invention discloses a method for synthesizing 2,3-dimethyl-6-amino-2H-indazole by microchannel hydrogenation, and belongs to the technical field of synthesis of pharmaceutical intermediates. The method comprises steps as follows: firstly, raw material 2,3-dimethyl-6-nitro-2H-indazole and a catalyst Pd/C are added to a solvent, a gel solution is prepared, the gel solution and hydrogen are fed into a microchannel reactor under the condition of certain pressure and temperature, and 2,3-dimethyl-6-amino-2H-indazole is synthesized by hydrogenation in a short time of tens of seconds to a few minutes. The method integrates the characteristics that a microchannel has efficient mass and heat transfer capabilities and is easy to amplify directly, the degree of hydrogenation can reach 99.5%, andproduct yield is higher than 98%. The method has higher operational safety and selectivity, can realize continuous production of reaction and has the advantages of low energy consumption, short reaction time, high safety, simple technological process, low production cost, no side reaction and the like.
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Paragraph 0025; 0026; 0027; 0028; 0029; 0030; 0031; 0032
(2019/03/10)
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- Hydrochloric acid [...] of the method for the preparation of intermediates
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The invention discloses a preparation method of an intermediate (2,3-dimethyl-N-(2-chloropyrimidine-4-base)-N-methyl-2H-indazole-6-amine) of pazopanib hydrochloride as shown in a formula I. The preparation method comprises the step of performing nucleophilic substitution reaction on a compound III and 2,4-dichloropyrimidine in an organic solvent under the action of alkali, wherein the reaction temperature is 0-160 DEG C. According to the preparation method disclosed by the invention, raw materials are low in price and easy to obtain, and the preparation method is convenient to operate, high in product yield and suitable for industrial large-scale production.
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- 2,3-dimethyl-6-urea -2H-indazoles and its preparation method and application
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The invention discloses a 2, 3-dimethyl-6-urea-2H-indazole compound shown by the following general formula (I), medicinal salt or a solvent compound thereof, wherein Ar is substituted or unsubstituted phenyl or aromatic matrix. The invention also discloses a preparation method and application of the compound. The compound can regulate signal transduction of tyrosine kinase, inhibit bad cellular proliferation, and particularly has obvious curative effect for tumors.
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- PROCESS FOR THE PREPARATION OF PAZOPANIB OR SALTS THEREOF
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The present invention provides a process for the preparation of pazopanib of Formula Ia or salts, and intermediates thereof.
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Paragraph 0035; 0036; 0037
(2016/01/08)
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- Discovery and synthesis of N2,N4-substitued- cycloalkyl[d]pyrimidine-2,4-diamine analogs: The first examples of small-molecular FGFR-1 activator
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A series of novel, cycloalkyl-modified pazopanib analogs 2 and 3 were designed and synthesized. Their kinase modulatory effects on FGFR-1, VEGFR-2, PDGFR-β, and c-KIT were evaluated by the caliper mobility shift assay. Introduction of cycloalkyl into the pyrimidine linker of pazopanib almost abolished the four kinases inhibitory potency of compounds 2 and 3, but surprisingly, resulted in good activation effects on FGFR-1. Compounds 3d and 3g showed double-digit, nanomolar, selective activation effects on FGFR-1, and could be classified as first-generation small molecular activators of FGFR-1 kinase.
- Li, Bao-Li,Xiao, Fang,Lu, Wen-Chao,Sun, Yu-Yun,Zhu, Jin,Li, Jian
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p. 989 - 994
(2014/08/18)
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- Synthesis and biological evaluation of novel pazopanib derivatives as antitumor agents
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A series of novel pazopanib derivatives, 7a-m, were designed and synthesized by modification of terminal benzene and indazole rings in pazopanib. The structures of all the synthesized compounds were confirmed by 1H NMR and MS. Their inhibitory
- Qi, Haofei,Chen, Ligong,Liu, Bingni,Wang, Xinran,Long, Li,Liu, Dengke
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p. 1108 - 1110
(2014/03/21)
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- A novel practical synthesis of pazopanib: An anticancer drug
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Abstract: This paper reports a novel approach to synthesize pazopanib. In our synthetic route, the potently mutagenic alkylating agents such as dimethyl sulfate and methyl iodide are avoided. A novel regioselective methylation of the 2- position of 3-methyl-6-nitro-1H-indazole was reported. This novel route is one step shorter than the previously reported route.
- Mei, Yi Cheng,Yang, Bao Wei,Chen, Wei,Huang, Dan Dan,Li, Ying,Deng, Xin,Liu, Bao Ming,Wang, Jing Jie,Qian, Hai,Huang, Wen Long
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p. 276 - 279
(2012/08/27)
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- METHODS FOR IDENTIFICATION OF JAK KINASE INTERACTING MOLECULES AND FOR THE PURIFICATION OF JAK KINASES
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The present invention relates to immobilization compounds and methods useful for the identification of JAK interacting compounds or for the purification or identification of JAK.
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Page/Page column 34; 1/10
(2009/06/27)
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- Treatment Method
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The present invention is directed to methods of treating an ocular neovascular disorder in a mammal by administration of pyrimidine derivatives, benzodiazepinyl derivatives and pharmaceutical compositions containing the same. The invention encompasses methods of treating an ocular neovascular disorder by administration of 5-[[4-[(2,3-Dimethyl-2H-indazol-6-yl)methylamino]-2-pyrimidinyl]amino]-2-methylbenzenesulfonamide, (S)-3-oxo-8-[3-(pyridin-2-ylamino)-1-propyloxy]-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydro-1H-2-benzazepine-4-acetic acid or salts or solvates thereof. Combination therapies for the treatment of ocular neovascular disorders are also encompassed.
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Page/Page column 9
(2009/01/20)
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- CANCER TREATMENT METHOD
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The present invention relates to a method of treating cancer in a mammal by administration of pyrimidine derivatives and quinazoline derivatives. In particular, the method relates to a method of treating cancer by administration of 5-[[4-[(2,3-dimethyl-2H-indazol-6-yl)methylamino]-2-pyrimidinyl]amino]-2-methylbenzenesulfonamide or salts or solvates thereof, and N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methane sulphonyl)ethyl]amino}methyl)-2-furyl]-4-quinazolinamine, or salts or solvates thereof.
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- CANCER TREATMENT METHOD
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The present invention relates to a method of treating cancer in a mammal by administration of pyrimidine derivatives. In particular, the method relates to a method of treating cancer by administration of 5-[[4-[(2,3-Dimethyl-2H-indazol-6-yl)methylamino]-2-pyrimidinyl]amino]-2-methylbenzenesulfonamide or a salt or solvate thereof.
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Page/Page column 27
(2008/06/13)
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- PYRIMIDIN DERIVATIVES FOR THE TREATMENT OF MULTIPLE MYELOMA
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The present invention relates to a method of treating cancer in a mammal by administration of pyrimidine derivatives and pharmaceutical compositions containing the same. In particular, the method relates to a method of treating multiple myeloma by administration of 5-[[4-[(2,3-Dimethyl-2H-indazol-6-yl)methylamino]-2-pyrimidinyl]amino]-2-methylbenzenesulfonamide or salts or solvates thereof.
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Page/Page column 14-15
(2010/10/20)
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- CANCER TREATMENT METHOD
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A method of treating cancer is described including administration of a pyrimidine derivative and a quinazoline derivative as well as a pharmaceutical composition including the same.
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- CHEMICAL PROCESS
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A process for the preparation of pyrimidine derivatives, which are useful as VEGFR2 inhibitors is described herein. The described invention also includes pyrimidine derivatives as well as methods of using the same in the treatment of hyperproliferative diseases.
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