97 results about "Saxagliptin" patented technology

The invention relates to the area of medicinal chemistry, pharmacology and medicine and includes description of pharmaceutical compositions and combined medicaments on the base of secretion stimulators and protectors of incretin hormones for treatment of metabolic diseases (among them, diabetes, obesity, metabolic syndrome and the like). The invention consists in that that pharmaceutical composition or combined medicament comprises a derivative of tetrahydrobenzo[f][1,4]oxazepine—either nonsteroidal agonist of bile aids receptor TGR5, or one of endogenous bile acids which stimulate incretin hormones secretion, and also one of the known inhibitors of DPP-IV proteinase. In this case administration of TGR5 agonists is carried out peroral, and administration of endogenous bile acids is exercised rectal in the form of suppository or gel. As proteinase DPP-IV inhibitors could be used Vildagliptin, Saxagliptin, Sitagliptin, Teneligliptin, Linagliptin, Dutogliptin, Alogliptin, Gemigliptin, Carmegliptin and the like. Besides, the invention includes description of novel tetrahydrobenzo[f][1,4]oxazepine derivatives—nonsteroidal agonist of bile aids receptors TGR5, and also methods for their preparation. The invention provides enhancement of therapy effectiveness owing to synergetic action of the components, thus making possible simultaneous treatment of diabetes, and obesity, other metabolic diseases and their cardiovascular and renal complications.

The invention provides a phenylalanine dehydrogenase (PDH) mutant derived from geobacillus, which is high in enzyme activity and thermal stability compared to wild PDH. Furthermore, the invention provides a method for catalytic synthesis of a saxagliptin chiral intermediate, namely (S)-N-t-butyloxycarbonyl-3-hydroxy-1-adamantyl-D-glycine (Boc-HAG) through the PDH mutant. According to the method provided by the invention, Boc-HAG can be directly prepared through a reaction in two steps, and e.e. (enantiomeric excess) value exceeds 99.9%; generation of side products can be reduced, yield of 95% can be achieved within 12 hours, catalysis time is greatly shortened, energy consumption is reduced and a post-treatment process is simplified.

The invention relates to an amino-protected 3-hydroxy adamantane glycine benzothiazole-2-thiol active ester as well as a preparation method and application thereof. The thiol active ester is prepared by virtue of reaction between amino-protected 3-hydroxy adamantane glycine and dibenzothiazyl disulfide. The invention further discloses application of the compound in the preparation of a saxagliptin intermediate and saxagliptin. The invention provides a brand new chemical structure. The preparation method is simple and low in cost; the compound is applicable to the preparation of saxagliptin, so that the preparation process can be effectively simplified; and the reaction is mild, and the compound has a wide generalization prospect.

The invention discloses a preparation method for saxagliptin. The preparation method for the saxagliptin uses a chemical synthesis method to replace saxagliptin intermediate preparation in a traditional technique and uses chiral inducer in the reaction to perform chiral synthesis. The preparatoin method for the saxagliptin is easy and convenient to operate, is high in yield, enables the intermediate production cost to be lowered and solves the technical problem of difficulty in biological enzyme preparing and storing due to the fact that the traditional technique needs to use biological enzyme to perform resolution.

The invention relates to a preparation method of a saxagliptin medicinal composition. The form of the above preparation can be safely applied to patients, can improve the stability of saxagliptin, and also can improve the gastrointestinal tract absorption. The invention concretely relates to a preparation method of a medicinal composition containing amorphous saxagliptin and beta-cyclodextrin. The preparation method comprises the following steps: grinding saxagliptin and beta-cyclodextrin under an alkaline condition, drying, crushing to obtain 150-250 mesh fine powder, mixing the powder with an appropriate auxiliary material to prepare granules, tabletting, and dressing to obtain the composition. The saxagliptin composition greatly improves the in vitro release in order to improve the bioavailability, can effectively treat type II diabetes, and has the advantages of convenient oral administration, covering of bad taste, fast disintegration, fast absorption and convenient carrying.

The invention discloses a melbine crystal and a medicinal composition of melbine and saxagliptin and a preparation method thereof. The medicinal composition consists of active ingredients of medicines and a pharmaceutic adjuvant, wherein the active ingredients of the medicines comprise the following components in part by weight: 5 to 30 parts of saxagliptin and 200 to 800 parts of melbine, and the melbine is the melbine crystal; and the pharmaceutic adjuvant comprises a filling agent, a disintegrating agent, an adhesive and a lubricating agent. The melbine crystal used in the medicinal composition has the characteristic of low solubility, so the sustained-release effect of the melbine is realized by using ordinary matrix materials in the medicinal composition prepared from the melbine andthe saxagliptin, the administration safety is improved; and the synergistic effect of the melbine and the saxagliptin is good, so the curative effect is improved. In addition, due to the adoption of few matrix materials, the stability of the medicines is improved.

The invention belongs to the technical field of the biological medicine, and specifically relates to a CAR-T cell, a reagent for enhancing capacity of homing CAR-T cell to solid tumor tissue, and application thereof. The reagent is a DPP4 inhibitor, includes but not limited to sitagliptin, vildagliptin, saxagliptin, alogliptin and linagliptin. The CAR-T cell expression includes ScFv, a hinge structure and a transmembrane structure, and a chimeric antigen receptor (CAR) of an intracellular activation signal domain; an amino acid sequence of the hinge structure is as shown in SEQ ID NO.1 or SEQID NO.2 or SEQ ID NO.3 or SEQ ID NO.4 or SEQ ID NO.5. The invention provides a new application of the DPP4 inhibitor for participating tumor treatment. The reagent can enhance the tumor homing capacity and tumor enrichment capacity of the CAR-T cell, and a therapeutic effect on the solid tumor by the CAR-T therapy is improved.

The invention provides a method for producing saxagliptin. The method comprises the following steps of: 1, providing a compound d; and 2, reacting the compound d, isopropanol and concentrated hydrochloric acid at the temperature of between 50 and 80 DEG C, and collecting the product to obtain the saxagliptin. Compared with the prior art, the method has the advantages that the compound d is directly converted into the target product, so that the reaction rate is greatly improved, the reaction yield is improved, the post treatment method is simplified, and industrial wastewater is greatly reduced.

The invention elates to the medicine synthesis field, and concretely relates to a preparation method of a saxagliptin intermediate. A technical scheme adopted in the invention is characterized in that a compound with the structure represented by formula (I) shown in the specification; and in the formula (I), M is hydrogen or various ether hydroxy protection groups, R1 and R2 are H or CH3 respectively independently, and at least one of R1 and R2 is H.

The invention discloses a novel saxagliptin medicinal preparation. The novel saxagliptin medicinal preparation comprises saxagliptin, acidic granules and lubricants. The acidic granules are made of fillers and acid. The novel saxagliptin medicinal preparation has the advantages that the shortcoming of instable properties of the saxagliptin can be effectively overcome by the aid of the novel saxagliptin medicinal preparation, degradation of the saxagliptin which is an active constituent can be reduced, and accordingly curative effects can be guaranteed.

The invention provides a method for preparing a saxagliptin intermediate 2 as shown in the specification. An existing process is improved by using the method, so that the yield and purity of a productare greatly increased, in addition, it is convenient realize aftertreatment, and the method is particularly suitable for industrial production.

The invention relates to the technical field of medicine midbody preparing and particularly discloses a saxagliptin midbody preparing method. The method includes the following steps that (R)-5-hydroxylpyrrole-2-ketone serves as a raw material, benzyl alcohol is used as a solvent, and 5-benzylhydroxylpyrrole-2-ketone is obtained through dehydration under the temperature of 70 DEG C to 80 DEG C; Boc is introduced for protection, reduction, dehydration and kulinkovich are conducted, IV compound is generated, debenzylation is conducted, methylsulfonyl is introduced, cyanogroup is introduced, and finally (1S,3S,5S)-3-(amino-carbonyl)-2-azabicyclo[3.1.0]hexane-2-tert-butyl formate is obtained through hydrolysis. According to the saxagliptin midbody preparing method, raw materials are easy and convenient to prepare, operation conditions are easy to control, the reaction yield is high, no pollution is generated, the selectivity of enantiomer is high, and the method is suitable for industrial production.

The invention discloses a preparation method of a saxagliptin intermediate (A1), and belongs to the field of chemical pharmacy. Adamantyloxoacetic acid is obtained through a Grignard reaction, hydrolysis and a mixed acid reaction with bromoadamantane as an initial raw material. The method has the advantages of simple and easy operation, high yield, small pollution, and suitableness for industrial production.

The invention discloses a method for preparing saxagliptin, and belongs to the technical field of drug synthesis. The method comprises the following steps: (a) converting amide on a compound shown ina formula I into cyano and removing Boc groups to obtain a compound shown in a formula II; (b) condensing the compound shown in the formula II and a compound shown in a formula III to obtain a compound shown in a formula IV; and (c) removing Boc groups on the compound shown in the formula IV to obtain a compound shown in a formula V. According to the method, different raw materials and reaction reagents are selected, and a process route is changed, so that four procedures of salifying, condensing, cyanating and de-protecting are shortened into three procedures of cyanating, condensing and de-protecting; meanwhile, cyanating and condensation reaction are realized at the room temperature, the requirements on reaction conditions are reduced, and industrial production can be realized.