Abstract: The invention provides a method for preparing a key intermediate for the synthesis of (S)-2-(3S,8S)-3-(4-(3,4-dichlorobenzyloxy)phenyl-7-((S)-1-phenylpropyl)-2,3,6,7,8,9-hexahydro-[1,4]-dioxino[2,3-g]isoquinolin-8-ylformylamino)-3-(4-(2,3-dimethylpyridin-4-yl)phenyl)propionic acid dihydrochloride: methyl (S)-2-amino-3-(4-(2,3-dimethylpyridin-4-yl)phenylpropionate and the salt thereof. The method adopts continuous feeding mode, does not require column chromatographic purification, simplifies the procedures, reduces loss and increases yield. Furthermore, the product, i.e., salt of methyl (S)-2-amino-3-(4-(2,3-dimethylpyridin-4-yl)phenylpropionate, obtained by the purification mode of salt formation, has high purity and good storage stability. The preparation method of the invention can achieve a total yield of above 85%, a purity of the target product of above 98%, and a content of the isomer of below 0.5%.

Abstract: The present invention relates to a method for preparing GLP-1 receptor agonist, specifically relates to an industrialized method for preparing a GLP-1 receptor agonist (S)-2-(3S,8S)-3-(4-(3,4-dichlorobenzyloxy)phenyl-7-((S)-1-phenylpropyl)-2,3,6,7,8,9-hexahydro-[1,4]-dioxino[2,3-g]isoquinolin-8-ylformylamino)-3-(4-(2,3-dimethylpyridin-4-yl)phenyl)propanoic acid dihydrochloride (compound I). The method utilizes compound 1 as the starting material, which undergoes nucleophilic addition, hydrolysis, reduction ammoniation, cyclization, amide condensation, hydrolysis, and salt forming reaction to give compound I. The method for preparing compound I has a total yield of more than 35%, with purity of compound I more than 98%.

Abstract: The invention provides a method for preparing a key intermediate for (S)-2-(3S,8S)-3-(4-(3,4-dichlorobenzyloxy)phenyl-7-((S)-1-phenylpropyl)-2,3,6,7,8,9-hexahydro-[1,4]-dioxino[2,3-g]isoquinolin-8-ylformylamino)-3-(4- (2,3-dimethylpyridin-4-yl)phenyl)propionic acid dihydrochloride, Methyl (S)-2-amino-3-[4-(2,3-dimethylpyridin-4-yl)-phenyl]-propionate diacid salt. Compared with the prior art, the method does not require column chromatographic separation and purification, has the advantages of low cost and high yield, and is suitable for industrial production.

Abstract: The invention relates the preparation method of a free base GLP-1 receptor agonist, specifically relates to preparation of (S)-2-(3S,8S)-3-(4-(3,4-dichlorobenzyloxy)phenyl-7-((S)-1-phenylpropyl)-2,3,6,7,8,9-hexahydro-[1,4]-dioxino[2,3-g]isoquinolin-8-ylformylamino)-3-(4-(2,3-dimethylpyridin-4-yl)phenyl)propionic acid free base. First, compound III is reacted with a condensation agent to give an active ester, and the amino organic acid salt is dissociated in situ and then directly involved in the amide condensation. Subsequently, in the hydrolysis, by means of the workup mode of acid-base neutralization, (S)-2-(3S,8S)-3-(4-(3,4-dichlorobenzyloxy)phenyl-7-((S)-1-phenylpropyl)-2,3,6,7,8,9-hexahydro-[1,4]-dioxino[2,3-g]isoquinolin-8-ylformylamino)-3-(4-(2,3-dimethylpyridin-4-yl)phenyl)propionic acid free base is precipitated from suitable solvent in high purity.

Abstract: The invention provides pharmaceutically acceptable acid salts of (S)-2-(3S,8S)-3-(4-(3,4-dichlorobenzyloxy)phenyl-7-((S)-1-phenylpropyl)-2,3,6,7,8,9-hexahydro-[1,4]-dioxino[2,3-g]isoquinolin-8-ylformylamino)-3-(4-(2,3-dimethylpyridin-4-yl)phenyl) propionic acid (“OAD2”) and the preparation method thereof. The pharmaceutically acceptable acid salts of OAD2 provided herein may be useful in the treatment of various conditions and metabolic disorders including, but not limited to, type 2 diabetes.

Abstract: The invention relates to a crystal form A of (S)-2-(3S,8S)-3-(4-(3,4-dichlorobenzyloxy)phenyl-7-((S)-1-phenylpropyl) -2,3,6,7,8,9-hexahydro-[1,4]-dioxino[2,3-g]isoquinolin-8-ylformylamino)-3-(4-(2,3-dimethylpyridin-4-yl)phenyl)propionic acid (“OAD2”) , and methods of preparation thereof. Crystal form A may be useful in the treatment of various conditions and metabolic disorders including, but not limited to, type 2 diabetes.

Abstract: The present invention relates to a chemical and pharmaceutical technology, and in particular to a STAT3 and ERK signal pathway inhibitor and a use thereof. The present invention provides a STAT3 and ERK signal pathway inhibitor. The inhibitor mainly consists of a mogroside and/or an analog thereof. The mogroside and the analog thereof inhibit the phosphorylation of a transcription factor STAT3 and the phosphorylation of an ERK. The method for preparing the mogroside and the analog has the characteristics of simpleness, strong operability and high purity of products. The present invention further provides a use of the STAT3 and ERK signal pathway inhibitor in the preparation of drugs for treating tumors, which realizes the purposes of inhibiting the proliferation of cancer cells and promoting the apoptosis of cancer cells and has a very good inhibition effect on cancers.