Les Laboratoires Servier

Shanghai Institute of Pharmaceutical Industry

Les Laboratories Servier

Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

China State Institute of Pharmaceutical Industry

Li, Min

Hanbin Shan

Zhedong Yuan

Xiong Yu

Yu Huang

Xueyan Zhu

Peng Zhang

Hongjuan Pan

Philippe Letellier

Xingdong Cheng

Hubo Wang

Michael Lynch

Xufeng Cao

Xudong Jiang

Ying Luo

Yuhui Shen

Meng Guo

Mingtong Hu

Min Li

Jean-Manuel Pean

Ling Tong

Yajun Guo

Duzheng Wang

Cécile Poirier

Cecile Poirier

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 relates to new forms of co-crystals of agomelatine and p-toluenesulphonic acid, to a process for their preparation and to pharmaceutical compositions containing them. The co-crystals according to the invention have better solubility than agomelatine and are therefore more suitable for the preparation of pharmaceutical compositions. They also have better stability and purity and, moreover, are obtained by a simple process which does not include any difficult steps. 

Forms of co-crystals of agomelatine and p toluenesulphonic acid, a process for their preparation and pharmaceutical compositions containing them

Complexes of agomelatine and sulphonic acids of formula (I):  Medicinal products containing the same which are useful in treating disorders of the melatoninergic system.

Complexes of agomelatine and sulphonic acids, a process for their preparation and pharmaceutical compositions containing them

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 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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Gaoan, China

Hanbin Shan