Les Laboratoires Servier

Shanghai Institute of Pharmaceutical Industry

Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Les Laboratories Servier

China State Institute of Pharmaceutical Industry

Nanjing Chia Tai Tianqing Pharmaceutical Co., Ltd.

Li, Min

Xiong Yu

Zhedong Yuan

Hanbin Shan

Yu Huang

Xueyan Zhu

Peng Zhang

Xingdong Cheng

Hongjuan Pan

Hubo Wang

Ling Tong

Xufeng Cao

Xudong Jiang

Ming Zhang

Martin Alsina Navarro

Andre Luiz Moreno

Meng Guo

Mingtong Hu

Min Li

Wenliang Zhou

Yajun Guo

Laifang Zhang

Yulei Yang

Duzheng Wang

Qing Long

Yaoqiang Wang

Disclosed are a method for preparing a dabigatran etexilate intermediate, and an intermediate compound. The method for preparing a dabigatran etexilate intermediate 4 comprises: reacting a compound 3 with a C-Calkyl alcohol solution of methylamine in an organic solvent, wherein, X=chlorine, bromine, or iodine. Also disclosed are an intermediate compound 3 and a preparation method thereof. The method for preparing a dabigatran etexilate intermediate of the present invention has the advantages of simple process, easy operation, high yield, and easy purification, thus being suitable for industrial production. 

Method for preparing dabigatran etexilate intermediate, and intermediate compound

The present invention provides a new crystalline form VII of agomelatine, its method of preparation, application and pharmaceutical composition. This new crystalline form offers high purity, a stable crystalline structure and good reproducibility, while its method of production lends itself well to large scale production. In terms of stability and purity, it is superior to the numerous crystalline forms which have hitherto been reported. As a result, the crystalline form VII of the present invention possesses advantages in pharmaceutical preparation.

Crystal form VII of agomelatine, preparation method and use thereof and pharmaceutical composition containing same

Provided are a compound of formula (I), pharmaceutically acceptable salts thereof, preparation methods and applications thereof for inhibiting thrombin, and applications in the treatment and prevention of thrombin-mediated and thrombin-related diseases.

Prolinamide derivatives as thrombin inhibitors, preparation method and application thereof

The present invention relates to the intermediate compounds for preparation of agomelatine, as well as the preparation methods thereof The intermediate of the present invention for preparation of agomelatine is compound A as shown in the following formula. Also provided are two novel intermediate compounds. When we use these new intermediate compounds to prepare agomelatine, it is simple to manipulate, well-controlled and with high purity, without complicated operations such as rectification and column chromatography separation, and suitable for industrial production. Meanwhile, the preparation methods of the two new intermediates themselves is simple and high yield, only using the most commonly-used 7-methoxy-tetralone as original starting material and undergoing one step of reaction to obtain the intermediates, followed by one more step of converting the intermediate compounds to desired product agomelatine. Said reaction processes are greatly simplified, with the reaction yield being improved and the difficulty in purification of previous method being overcome, as compare with the previous technique for preparation of agomelatine. Typically, the yield of the present invention is over 70%. 

Agomelatine intermediates and preparation method thereof

The present application discloses crystals of 2-acetoxy-5-(&#x3b1;-cyclopropylcarbonyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine hydrobromate, crystal compositions and pharmaceutical compositions comprising them and their use. The crystals of prasugrel hydrobromate of the present application possess excellent stability and solubility.

Crystals of prasugrel hydrobromate

The present invention relates to an agomelatine hydrobromide hydrate of formula I wherein X is Br, preparation and use thereof, and to pharmaceutical compositions containing it. The agomelatine hydrobromide hydrate obtained through the present method has significant increased solubility than agomelatine, and therefore is more suitable for manufacturing pharmaceutical formulations. In addition, the product enjoys higher stability and purity. Using the present method, product of high purity can be obtained through a simple process, free of any complicated steps.

Agomelatine hydrobromide hydrate and preparation thereof

The present invention relates to an agomelatine hydrochloride hydrate of formula I, preparation and use thereof, and to pharmaceutical composition containing it. The agomelatine hydrohalide hydrate obtained through the present method has significant increased solubility than agomelatine, and therefore is more suitable for manufacturing pharmaceutical formulations. In addition, the product enjoys higher stability and purity. Using the present method, product of high purity can be obtained through a simple process, free of any complicated steps. wherein X is Cl.

Agomelatine hydrochloride hydrate and preparation thereof

The invention provides a new crystalline form of agomelatine, preparation and use thereof. The X-ray powder diffraction diagram of the agomelatine crystalline form shows main peaks at the diffraction angles 2&#x3b8; 11.13&#xb0;, 11.82&#xb0;, 17.49&#xb0;, 18.29&#xb0;, 19.48&#xb0;, 19.72&#xb0;, 20.50&#xb0;, 21.76&#xb0;, 22.54&#xb0;, 22.97&#xb0;, 24.56&#xb0;, 25.36&#xb0;, 27.16&#xb0; and 31.93&#xb0;. Said new crystalline form is characterized by high purity, stability and good reproducibility, and thus is advantageous for the pharmaceutical formulation. In addition, the stability and solubility of said crystalline form are also superior over the several existing crystalline forms.

Crystalline form VI of agomelatine, preparation method and application thereof

The present invention relates to a complex of agomelatine and to preparation thereof. The hydrogen halide complex of agomelatine obtained through the present method is more soluble, more stable, and of higher purity than agomelatine itself, making it more suitable to be used in pharmaceutical preparation. Using this method, product of high purity can be obtained through a simple process, without having to incur further complicated steps.

Agomelatine hydrohalide complex and preparation method thereof

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Shanghai, China

Xiong Yu