IMIGLIPTIN, NEW PATENT, WO 2017211293, XUANZHU PHARMA CO., LTD.

(WO2017211293) CRYSTALLINE FORM OF SUCCINATE USED AS DIPEPTIDYL PEPTIDASE-4 INHIBITOR 
WO-2017211293, 
XUANZHU PHARMA CO., LTD. [CN/CN]; 2518, Tianchen Street, National High-Tech Development Zone Jinan, Shandong 250101 (CN)
SHU, Chutian; (CN)


https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2017211293&recNum=1&tab=PCTDocuments&maxRec=&office=&prevFilter=&sortOption=&queryString=

The present invention relates to a crystalline form of a succinate used as a dipeptidyl peptidase-4 inhibitor, and a manufacturing method, pharmaceutical composition, and application thereof. The invention specifically relates to a dipeptidyl peptidase-4 inhibitor compound as represented by formula (1), a crystalline form of a succinate, wherein the succinate is an (R)-2-((7-(3-aminopiperidin-1-yl)-3,5-dimethyl-2-oxo-2,3-dihydro-1H-imidazo(4,5-b)pyridin-1-yl)methyl)benzonitrile, and a manufacturing method, pharmaceutical composition, and application thereof. Example 1: Preparation of the succinate salt form I of the compound of formula (1) [0056] [0057] The compound of formula (1) (44.6 g, 0.12 mol) was added to a 2 L round bottom flask and suspended in 1593 mL of acetonitrile. The mixture was heated to 80 ° C. and dissolved in free form. Immediately after the addition of 15.4 g A white solid precipitated, maintained at 80 ℃ for 1 hour and then cooled to room temperature, filtered and the filter cake was dried in vacuo at 40 ℃ for 10 hours, weighed 57.6g, yield 98.3%. The succinate salt Form I was tested by XRPD. [0058] Example 2: Preparation of the succinate salt form I of the compound of formula (1) II [0059] A quantity of succinate salt of the compound of formula (1) was weighed into glass vials in a total of 26 parts. A total of 26 vials of methanol, ethanol, isopropanol, isobutanol, 2-butanone, tetrahydrofuran, acetonitrile, methyl tert-butyl ether, acetone, water, toluene, Isopropyl acetate, n-propanol, isoamyl alcohol, butyl acetate, ethyl formate, 1,4-dioxane, n-butanol, pentane, heptane, cyclohexane, Ketone, xylene, isobutyl acetate, diethyl ether). After stirring, ultrasound and other means to make the sample fully dissolved. Subsequently, about 2 mL of liquid was removed from each bottle and filtered into 26 reagent tubes numbered 1-26. The resulting 26 filtrates were distributed in two 96-well plates. One or two of the above 1-13 solvents are sequentially added into the first 96-well plate, one or two of the above-mentioned 14-26 kinds of solvents are sequentially added into the second 96-well plate, Zha Kong sealing film sealed, placed in a fume hood, the natural environment to dry. Wherein Form I is obtained in the following mixed solvent, and Form I is also precipitated in the methyl isobutyl ketone in the remaining solution after plating. [0060] The solvent used to prepare succinate salt Form I was prepared [0061] [Table 0001] Mixed solvents Solvent 1 Solvent 2 1 Methyl isobutyl ketone Ether 2 Xylene Ether 3 Isobutyl acetate Ether 4 Ether Ether 5 1,4-dioxane Pentane 6 1,4-dioxane Heptane 7 1,4-dioxane Cyclohexane 8 1,4-dioxane Methyl isobutyl ketone 9 1,4-dioxane Xylene 10 1,4-dioxane Isobutyl acetate 11 Butyl acetate Ether 12 Butyl acetate 1,4-dioxane [0062] Example 3: Preparation of the succinate salt form II of the compound of formula (1) [0063] Take 8 parts of the compound of formula (1), 200mg each, placed in a 10mL round bottom flask, add the solvent in the following table to each solvent, warmed until the solvent is refluxed, after dissolving it, add 69mg (1.1eq) succinic acid and cool to At room temperature, the solid precipitated and was filtered. The resulting solid was subjected to XRPD testing as succinate crystal form II. [0064] [Table 0002] Feeding amount Solvent and ratio 2mL Tetrahydrofuran 3mL acetone 5.5mL Acetonitrile: water = 10: 1 2mL Methanol 4mL Ethanol 1mL Ethanol: water = 10: 1 2mL Isopropanol: water = 19: 1 2mL Isopropyl alcohol: water = 9: 1

New patents, 19 DEC 2017

Sr no	Patent number	name	company	INDICATION	REMARKS, WAIT FOR STR TO APPEAR
1	WO-2017212390	LANREOTIDE	EMCURE	Acromegaly; Carcinoid syndrome; Gigantism; Neuroendocrine tumor
2	WO-2017212030	ASTAXANTHIN	DEINOVE	Aging; Cancer; Cardiovascular disease; Central nervous system disease; Diabetes mellitus; Inflammatory disease
3	WO-2017211820	DEOXYCHOLIC ACID	BIONICE	Cholelithiasis; Hepatitis; Liver disease; Primary biliary cirrhosis
4	WO-2017211788	PALBOCICLIB	KHS	Metastatic breast cancer
5	WO-2017211777	NINTEDANIB	OLON	Idiopathic pulmonary fibrosis; Small-cell lung cancer
6	WO-2017211733	SUVOREXANT	ENANTIA	Insomnia
7	WO-2017211325	TENOFOVIR	SHANGHAI	HIV infection; Hepatitis B virus infection
8	WO-2017211293	IMIGLIPTIN	XUANGHU	Hyperglycemia; Hyperlipidemia; Insulin resistance; Non-insulin dependent diabetes
9	WO-2017211248	COPANLISIB	SHENZEN	Cancer; Cardiovascular disease; Inflammatory disease; Neurodegenerative disease
10	WO-2017211246	ALCAFTADINE	SHENZEN	Allergy; Nasal congestion
11	WO-2017211245	RIBOCICLIB	SHENZEN	Glioma; Leukemia; Pancreas tumor
12	WO-2017211268	ABEMACICLIB	SHANGHAI	Autoimmune disease; Cancer; Inflammatory disease

New patents 12 Dec 2017

New patents 

Sr no	Patent number	name	company	INDICATION	REMARKS, WAIT FOR STR TO APPEAR
1	US-20170349608	RIFAXIMIN	ZYDUS CADILA	Diarrhea; Diverticulosis; Escherichia coli infection; Hepatic encephalopathy; Hyperammonemia; Intestine infection; Irritable bowel syndrome
2	WO-2017210261	FEVIPIPRANT	CONCERT	Allergic rhinitis; Asthma; Atopic dermatitis
3	WO-2017208258	GADOXETATE	BIOPHORE	Liver tumor
4	WO-2017208253	IVACAFTOR	CSIR	Cystic fibrosis
5	WO-2017208251	BREXPIPRAZOLE	CIPLA	Major depressive disorder; Schizophrenia
6	WO-2017208169	BETRIXABAN	REDDYS	Thromboembolism
7	WO-2017208165	OBETICHOLIC ACID	REDDYS	Primary biliary cirrhosis
8	WO-2017208156	ELUXADOLINE	SUN	Diarrhea predominant irritable bowel syndrome
9	WO-2017208132	GALETERONE	INDUSTRIALE	Prostate tumor
10	WO-2017208105	DOLUTEGRAVIR	LUPIN	HIV infection
11	WO-2017207648	OBETICHOLIC ACID	BIONICE	Primary biliary cirrhosis
12	WO-2017206808	DAPAGLIFLOZIN	CHINA SIP	Non-insulin dependent diabetes
13	WO-2017206689	LINAGLIPTIN	SHENZEN	Non-insulin dependent diabetes
14	WO-2017206688	OMBITASVIR	SHENZEN	Hepatitis C virus infection