43 results about "Omarigliptin" patented technology

The invention relates to novel omarigliptin salt and crystal form products of the omarigliptin salt, and belongs to the technical field of pharmaceutical chemicrystallization. Compared with existing omarigliptin crystal form products, the omarigliptin salt and the crystal form products of the omarigliptin salt have the advantages of being better in crystal form product stability and solubility, higher in dissolving rate and the like, the bioavailability of medicine can be improved, and the omarigliptin salt and the crystal form products of the omarigliptin salt are better suitable for an application of a solid preparation. The invention also relates to the omarigliptin salt, a preparing method of the crystal form products of the omarigliptin salt, a pharmaceutical composition of the omarigliptin salt and applications of the omarigliptin salt to medicine for treating type 2 diabetes mellitus.

The invention discloses a quinoline derivative or pharmacologically acceptable salt shown as a formula I (The formula is shown in the description), wherein R1, R2, R3 and R4 are respectively selectedfrom H or CH3. The compound listed in an in vitro DPP-4 enzyme inhibition test on the inhibition activity of DPP-4 is between Sitagliptin and omarigliptin. The quinoline derivative shown as the formula I disclosed by the invention is a DPP-4 inhibitor with a novel structure type, and the characteristics of the quinoline derivative in pharmacological toxicology and pharmacokinetics deserve more in-depth study, so that drugs used for treating and / or preventing non-insulin-dependent diabetes, hyperglycemia or insulin resistance can be obtained.

The invention discloses Omarigliptin and a preparation method of an intermediate of the Omarigliptin, and provides a preparation method of an Omarigliptin intermediate I. The preparation method comprises the following step: enabling a compound II and a compound III to undergo a condensation reaction in a polar aprotic organic solvent in the presence of lewis acid and sodium borohydride acetate to obtain the Omarigliptin intermediate I. The preparation method disclosed by the invention has the advantages of simple and safe operation, no need of special purification equipment, short reaction time, fewer by products, high yield and simple post treatment operation; column chromatography separating operation in a post treatment process is avoided; a prepared product is high in purity, the optical purity is greater than or equal to 99,9 percent, the purity of a related substance is greater than or equal to 98.5 percent, and the purities of all impurities are smaller than or equal to 0.5 percent separately; the preparation method is low in production cost and is suitable for industrial production. In addition, according to the Omarigliptin prepared from the Omarigliptin intermediate I obtained by adopting the preparation method disclosed by the invention, the purity is greater than or equal to 99.5 percent, the purities of all the impurities are smaller than or equal to 0.1 percent separately, and the standards of crude drugs are reached. (The formula is shown in the description).

The invention discloses a quinoline derivative represented by formula I, or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R4, and R5 are used for representing groups independently selected from H or CF3. In in vitro DPP-4 enzyme inhibition experiment, the IC50 value of the quinoline derivative on DPP-4 is lower than that of omarigliptin and sitagliptin. It is shown that the quinoline derivative possesses excellent DPP-4 inhibition activity, and can be used in preparation of drug used for treating and / or preventing non-insulin-dependent diabetes, hyperglycemia, or insulin resistance.

The invention discloses a compound shown in a formula I or pharmaceutically acceptable salts of the compound; the formula I is described in the description, wherein R1, R2, R3, R4 and R5 are independently selected from H or CF3. The IC50 values, for the dipeptidyl peptidase-IV (DPP-4), of compounds listed in in-vitro DPP-4 enzyme inhibition tests are less than those of omarigliptin and Sitagliptin. The compound provided by the invention is proved to have better DPP-4 inhibitory activity, thus being used as a medicine for treating and / or preventing non-insulin-dependent diabetes, hyperglycemiaor insulin resistance for further study.

The invention discloses a compound or pharmaceutically acceptable salt thereof shown as a formula I (the formula l is shown in the following description), wherein R1, R2 and R3 are each independentlyselected from H or OCH3. In an in-vitro DDP-4 enzyme inhibition test, IC50 values of listed compounds to DDP-4 are all smaller than omarigliptin and Sitagliptin. The test shows that the compound provided by the invention has better DDP-4 inhibition activity and can be used for deeper study as a drug for treating and / or preventing non-insulin-dependent diabetes mellitus, hyperglycemia or insulin resistance.

The invention provides a preparation method of an alogliptin intermediate, comprising, raw material A 2-(2,5-difluorophenyl)-2-oxoethylcarbamate alkyl ester, and raw material B alkyl sulfonate Acid propargyl ester reaction, obtains product C 1-(2,5-difluorophenyl)-1-oxopent-4-yn-2-ylcarbamate alkyl ester. The present invention has a unique approach, selects a specific alogliptin intermediate as a research direction, provides an efficient process, and the one-step reaction yield can be as high as 96%.