前苏联专利SU1507211A3 Method of producing pyridine derivatives

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专利摘要:
The compound of the formula wherein R1 is hydrogen, methoxy or trifluoromethyl, R2 and R3 are independently hydrogen or methyl, R" is a C2-5 fluorinated alkyl and n denotes 0 or 1, or a pharmacologically acceptable salt thereof is novel, and useful for prophylaxis and therapy of digestive ulcers (e.g. gastric ulcer, duodenal ulcer) and gastritis.
公开号:SU1507211A3
申请号:SU3947161
申请日:1985-08-14
公开日:1989-09-07
发明作者:Нохара Акира；Маки Еситака
申请人:Такеда Кемикал Индастриз, Лтд (Фирма)；
IPC主号:

专利说明:

R.
OR .3
R. Ill
XfH; N
where R, is hydrogen, methoxy or trifluoromethyl)
R and Rj are H or CHj;
R - fluorinated C-C-alkyl
one of X and Xj is a halogen atom, and the other is the SH group,
followed, if necessary, by the oxidation of the resulting pyridine sulfide derivative (1), where, with peracid, into the sulfinyl pyridine derivative, where n 1.
The reaction of compounds (II) and (III) is preferably carried out in the presence of a base. Alkali metal hydride, for example, sodium or potassium hydride, alkali metal, for example sodium metal, sodium alkoxide, for example sodium methoxide or ethoxide, alkali metal carbonate, for example potassium or sodium carbonate, and organic amines, for example triethylamine, can be used as the base. An example of a solvent used for the reaction is alcohols, for example methanol and ethanol, as well as dimethylformamide. The base is usually used in a slight excess compared to the required equivalent amount. You can, however, take in large excess. Thus, in particular, the base is taken in an amount of 1-10, preferably 1-4 equivalents. The reaction is usually carried out at a temperature of from about 3 ° C to the boiling point of the solvent used, preferably in the range of 20 °. The reaction time is 0.2-24, preferably 0.5-2 hours.
Examples of suitable oxidation peracids of the compound of the formula (D (n - 0) are m-chloroperbenzoic, peracetic, trifluoro-articular, and permaleic acid. Examples of the solvent used for the oxidation reaction are halogenated hydrocarbons, for example chloroform and dichloromethane - tan, ethers, for example tetrahydrofuran and dioxane, amides, for example dimethylformamide, alcohols, for example methanol, ethanol, propanol and
, ten
15
20
25
thirty
35
114
-butanol, or water. These solvents may be used alone or in mixture with each other. It is preferable to use an oxidizing agent in an equivalent or slightly higher amount than an equivalent amount with respect to the compound of formula (1) (). In particular, it is taken in an amount of 1-3, preferably 1-5 equivalents. The reaction is carried out at a temperature of from below 0 ° C to the boiling point of the solvent used, preferably at a temperature of from below 0 ° C to room temperature, most preferably at. The reaction time is about 0.1-24, preferably O, 1-4 hours.
The target compound of formula (1) obtained in this way can be isolated from the reaction mixture and purified in the usual way, for example, by recrystallization and chromatography.
The starting compounds of formula (111) can be prepared as follows.
Method 1.
SW-F.
) J
J; n, s N rt
i (v
AP N (VI)
40
45
O-RI
-o CHjCOCHj N / yjj y
-
HOCHzN CVlll)
0
(ni)
The nitro compound of formula (IV), in which RI and Kd have the definitions given, is reacted with an alcohol RjfOH of formula (V), in which R has the definition given, in the presence of a base, resulting in the alkoxy derivative of formula (VI), in which RI , Rj and R are defined. Examples of the base are an alkali metal, for example lithium, sodium or potassium, an alkali metal hydride, for example sodium or potassium hydride, an alkali metal alcoholate, for example potassium t-butoxide or sodium propoxide, an alkali metal carbonate or carbonate. or lithium, or potassium or sodium bicarbonate, or an alkali metal hydroxide, for example, sodium hydroxide or potassium hydroxide. Examples of the solvent used for the reactions include, in addition to R40H, ethers such as tetrahydrofuran and dioxane, as well as ketones, such as acetone and methyl ethyl ketone, acetonitrile, dimethylformamide and hexamethylphosphoric triamide. The reaction is carried out at a temperature of from below 0 ° C to about the boiling point of the solvent used. The reaction time is usually about 1-48 hours.
The compound of formula (VI) thus obtained is heated (at a temperature of about 80-120 s) in the presence of acetic anhydride alone or in a mixture with a mineral, for example sulfuric or perchloric acid, resulting in the formation of a 2-acetoxy methylpyridine derivative of the formula VII), in which R, R 3 and R 4 have the above definitions. The reaction time is usually about 0.1-10 hours.
Thereafter, the resulting compound of formula (VII) is subjected to alkaline hydrolysis, resulting in the formation of a 2-hydroxymethylpyridine derivative of formula (VIII), in which R, Rj and R have a reduced definition. Examples of alkali are sodium and potassium hydroxides, as well as sodium and potassium carbonates. Examples of the solvent used for the reaction are methanol, ethanol and water. The reaction is usually carried out at a temperature of about 20-60 ° C. The reaction time is about 0.1-2 hours.
The compound referred to the formula (VIII) is further reacted with an acidifier, for example, an organic sulfonic acid chloride, in particular, methane sulfonyl chloride or (p-toluenesulfonic acid or chlorohydride) or an acid chloride, As a result of this reaction, a compound of formula (III) is formed. The amount of chlorinating agent used to carry out the reaction usually ranges from one equivalent to a large excess with respect to the compound of formula (VIII). Examples of the solvent used for carrying out the reaction are chloroform, dichloromethane and tetrachloroethane. The reaction is usually carried out at a temperature of from 20 to 8 ° C. The reaction time is about 0.1 -2 hours
The acid chloride of an organic phosphoric or organic sulfonic acid is usually taken in an equivalent or slightly higher than the equivalent amount. The reaction is usually carried out in the presence of axis. Examples of the base can be organic, e.g. triethyl amine and tributylamine, or inorganic, e.g. sodium carbonate, potassium carbonate and sodium bicarbonate, bases. The base is usually taken in an equivalent or slightly larger than the equivalent amount. Examples of the solvent used to carry out the reaction include chloroform, dichloromethane, carbon tetrachloride or acetonitrile. The reaction is usually carried out at a temperature from below to a temperature close to the boiling point of the solvent used. The duration of the reaction is usually from several minutes to several hours. Preferably, the compound of formula (III) thus obtained is immediately used for the reaction with the compound of formula (II). Method 2
NOi OR
TH .. ITT
1m N
{four
. OO
(Ix)
P
-:
MeOSOj OSS

In the case of a reaction analogous to that described in process 1, a compound of formula (IX) in which RJ and R have the definitions given is converted to a compound of formula (X) in which Rj and R have the definitions given.
Thereafter, the resulting compound of formula (X) is subjected to a methylation reaction with dimethyl sulfate, which results in the formation of a compound of formula (XI) in which R-1, R g and R have the definitions given. The reaction can be carried out without solvent. The temperature at which the reaction is carried out is in the range of 100-120 seconds. The reaction time is about 0.1-4 hours.
Thereafter, the compound of formula (XI) is reacted with a source of radicals, for example ammonium persulphate or other persulphate in methanol, resulting in the formation of a compound of formula (VIII). The reaction is carried out at a temperature of about 20-80 ° C. The reaction time is approximately one hour.
Example 1. Dissolve 2 g of 2,3-dimethyl-4-nitropyridine-1-oxide in 10 ml of 2,2,3,3-tetrafluoropropanol and add 1.6 g of tert. To room solution in small portions at room temperature. potassium butoxide. The mixture is then heated at 80-90 ° C for 22 hours, diluted with water and extracted with chloroform. The extract is dried over magnesium sulfate and concentrated. The concentrate is subjected to chromatography on a column filled with 70 g of silica gel. Elution is carried out with a mixture of methanol and chloroform in a ratio of 1:10. Recrystallization of the obtained product is carried out from a mixture of ethyl acetate and hexane. As a result, 2.6 g of 2,3-dimethyl-4- (2,2,3, 3-tetrapoft-pro-propoxy) pyridine-1-oxide are obtained in the form of colorless needles, so pl. 138-139 C.
Similarly, compounds of formula (VI) are obtained from compounds of formula (IV) (see Table 1).
Example 2. A mixture of 2.0 g of 2,3-α-dimethyl-4-nitropyridine-1-oxide, 20 ml of methyl ethyl ketone, 3.05 ml of 2,2,3,3,3-pentafluoropropanol, 3.29 g of anhydrous potassium carbonate and 2.07 g of hexamethylphosphoric triamide

0 Q
e
0
heated for 4.5 days at 70 with stirring and the insoluble residue was filtered off. The filtrate is concentrated and water is added to the concentrate. The resulting mixture is subjected to abstraction with ethyl acetate. The extract solution is dried with magnesium sulfate and the solvent is distilled off. The residue is subjected to chromatography on a column filled with 50 g of silica gel. Elution was carried out with a mixture of chloroform and methanol in a ratio of 10: 1. After recrystallization of the product from a mixture of ethyl acetate and cyclohexane, 2.4 g of 2,3-dimethyl-4- (2,2,3,3,3-pentafluoro-propoxy) pyridine-1-oxide are obtained in the form of colorless needles, t. mp. 148-149 ° C. In a similar manner, using the compounds of formula (IV) as the starting material, compounds of formula (VI) are obtained (see Table 2).
Example 3. To a solution of 2.6 g of 2,3-dimethyl-4- (2,2,3,3-tetrafluoropropoxy) pyridine-1-oxide in 8 ml of acetic anhydride, 2 drops of concentrated hydrochloric acid are added, the mixture is stirred for 4 hours at and then concentrated. The residue is dissolved in 20 ml of methanol and 5 ml of water are added to the resulting solution; The mixture is stirred for 30 minutes at room temperature, after which it is subjected to extraction with ethyl acetate. The extract is dried with magnesium sulfate and then the solvent is distilled off. The residue is subjected to chromatography on a column filled with 50 g of silica gel. Elution was carried out with a mixture of chloroform and methanol in a ratio of 10: 1. After recrystallization of the product from isopropyl ether, 1, 6 g of 2-hydroxymethyl-3-methyl-4- (2,2,3,3-tetrafluoropropoxy) pyridine is obtained in the form of yellow crystals, m.p. 67-68 C.
In a similar way, using the compounds of formula (VI) as starting material, compounds of formula (VHI) are obtained (see table 3).
Example 4. To a solution of 2.0 g of 3,5-dimethyl-4-nitropyridine-1-oxide in 10 g of 2,2,3,3,3-pentafluoropropanol was added in small portions over 15 minutes to 2 g of tert-butoxide. Kali. The mixture is stirred for 18 hours at 60 ° C, after which chlorine is added.
reform, and filtered through celite. The filtrate is subjected to chromatography on a column filled with 80 g of silica gel. The elution was carried out with a mixture of ethyl acetate and hexane in a 1: 1 ratio, followed by 20% methanol in ethyl acetate. After recrystallization of the product from a mixture of ether and hexane, 2.6 g of 3,5-dimethyl-4- (2,2,3,3,3-pentafluoropropoxy) pyridine-1-oxide are obtained in the form of crystals with m.p. 89-91 S.
In a similar way, using the compounds of formula (IX) as starting material, compounds of formula (X) are obtained (see table 4).
Example 5. A mixture of 2.5 g of 3,5-dimethyl 4- (2,2,3,3,3-pentafluoropropoxy) pyridine-1-oxide and 1 ml of dimethyl sulfate is heated for 30 minutes at 120 ° C, after which 12.5 ml of methanol are added. A solution of 4.3 g of ammonium persulphate in a mixture of 20 ml of methanol and 10 ml of water is added dropwise to the mixture over 30 minutes and stirred for an additional 30 minutes, after which the resulting solution is concentrated. Ice was added to the residue and neutralized with sodium carbonate, followed by extraction with chloroform. The extract is dried with sodium sulfate and the solvent is distilled off. The result is 2.2 g of 3,5-dimethyl-2-hydroxymethyl-4- (2,2,3,3,3-penta fluoropropoxy) pyridine as an oily liquid.
In a similar way, using the compounds of formula (X) as starting material, compounds of formula (VIII) are obtained (see table 5).
Example 6. To a solution of 350 mg of 2-hydroxymethyl-3-methyl-4- (2,2,3,3,3-pentafluoropropoxy) p1 idin in 10 ml of chloroform was added 0.2 ml of thionyl chloride, boiling the mixture is refluxed for 30 min and concentrated. The residue is dissolved in 5 ml of methanol and the resulting solution is added to a mixture of 200 mg of 2-mercaptobenzimidazole, 1 ml of 28% sodium methoxide solution and 6 ml of methanol and the mixture is boiled for 30 minutes under reflux. . Methanol was distilled off from the resulting reaction mixture, water was added to the residue, and extraction was performed with ethyl acetate. Extract extract diluted hydroxide solution
0
five
0
g 0
five
five
0
5 0 5
sodium and dried with magnesium sulfate. The solvent is distilled off and the residue is subjected to chromatography on a column filled with 20 g of silica gel. The elution is carried out with a mixture of ethyl acetate and hexane in a 2: 1 ratio. After recrystallization of the product from a mixture of ethyl acetate and hexane, a hemihydrate of 370 mg of 2- 3-methyl-4- (2,2,3,3,3-pentafluoropropoxy) pyrid-2-yl 1-methylthiobenzimidazole is obtained in the form of colorless records with so pl. 145-1A6 S.
Similarly, by reacting compounds of formula (II) and (III), compounds of formula (I) are obtained (see table 6).
Example 7. To a solution of 2.2 g of 2-Cz-methyl-4- (2,2,3,3,3-peitafluoropropoxy) pyrid-2-yl methylthiobenzimidazole in 20 ml of chloroform is added dropwise to for 30 minutes under ice cooling, a solution of 1.3 g of m-chlorobenzoic acid in 15 ml of chloroform. The solution is then washed with a saturated aqueous solution of sodium bicarbonate, dried with magnesium sulfate and concentrated. The residue is subjected to chromatography on a column filled with 50 g of silica gel. Elution is carried out with ethyl A; After recrystallization of the product from a mixture of acetone and isopropyl ether, 1.78 g of 2- 3-methyl-4- (2,2,3,3,3-pentafluoropropoxy) pyrid-2-yl-methylsulphinylbenzimidazole are obtained in the form of a palette. yellow Tykh Lrizm, so pl. 16t-163 C (with decomposition).
Similarly, from the compounds of formula (I) (), compounds of formula (I) () are obtained (see Table 7).
Pharmacological action of the proposed compounds. As models of gastrointestinal ulcers, water-immersioin was used, induced by stress and with restriction of the movements of the pharynx, induced by indomethacin, and etiola-induced wounds of the gastric mucosa.
Experimental technique. Seven-week-old male Sprague-Dawley rats were not allowed to eat for 24 hours. Thereafter, the test compounds were injected into the animals into the stomach using a gastric probe. After 30 minutes, indomethacin was administered subcutaneously in the amount of 30 mg / kg. Within 30- 90 min after administration of indomethacin
given plenty of food pills (Japan, Clea, CE-2). Five hours after the administration of indomethacin, 1 ml of 1% Evans blue was injected into the tail vein and then they were killed with carbon dioxide gas. In killed animals, the stomach was removed from the lower esophagus and duodenum. The esophagus was pinched, 10 ml of a 1% formalin solution was injected into the stomach through the duodenum, after which the duodenum was also pinched and the entire stomach was immersed in a 1% formalin solution. After 15 minutes, the stomachs were opened along a larger curve. The area of wounds in the gastric mucosa was determined with a sample of an anatomical microscope with a square grid in the ocular (10). The total number of wounds in each animal was determined and the average value for each group was calculated. The rate of inhibition was determined by the difference between the mean values of each of the test and control groups. The test compounds and indomethacin were suspended in a 5% solution of gum arabic and administered in an amount of 2 ml / kg (see table 8).
As can be seen from the above data, the proposed compounds have a higher antiulcer activity (approximately 1.5–20 times or more) as compared with the known compounds. In addition, the compounds of formula (I) have a high inhibitory effect on the secretion of gastric acid, thereby protecting the gastric mucosa and preventing ringing.
As regards the toxicity of the compounds of formula (I), when orally administered to the compounds of the compound used in the experiments to determine anti-ulcer activity (compound in which R 1 Hj R g CHj j R - N; R - n 1), even in the amount of 2000 mg / kg was not fatal, i.e. The compounds of formula (1) are of low toxicity.
As mentioned, the compounds of formula (I) have a controlling effect on the release of gastric acid, have anti-ulcer activity and have a protective effect
five
0
five
0
five
0
five
0
five
effect on the mucosa. In addition, they have low toxicity and are relatively stable chemical compounds. Therefore, the compounds of formula (1) can be used to prevent and treat digestive ulcers (for example, stomach and duodenal ulcers) and gastritis in mammals (for example, mice, rats, rabbits, dogs, cats, and humans).
When compounds of formula (1) are used as anti-ulcer drugs for treating digestive ulcers in mammals, they can be administered orally in the form of capsules, tablets, granules, etc. in which they are combined with a pharmaceutically acceptable carrier, inert filler, diluent, etc. Their daily dose is about 0.01-30, preferably about 0.1-3 µg / kg.
Thus, the compounds obtained by the method have an improved anti-ulcer effect and can be used for the prevention and treatment of ulcers of the digestive organs (for example, ulcers of the stomach or duodenum) and gastritis.
Example 8. K2.2 g of 2-hydroxymethyl-4- (2,2,2-trifluoroethoxy) pyridine in chloroform (30 ml) was added 1.1 ml of thionyl chloride. After heating the mixture for 10 minutes, the formed crystals are filtered. The crystals and 0.95 g of thiourea in ethanol (30 ml) are heated and refluxed for 2 hours, then 6N is added. sodium hydroxide solution, the resulting mixture is heated and def.pegmicized for 1 h in a stream of nitrogen. 7 ml of 1N was added to the obtained product. hydrochloric acid and 5 ml of water.
The resulting mixture was extracted with ethyl acetate, washed with water and then dried over magnesium sulphate, after which the solvent was evaporated, 6 n was added. hydrochloric acid in methanol (5 ml) and then the solvent is evaporated. Diethyl ether is added to the obtained residue, crystallized, filtered and dried, yielding 2.1 g of 3-methyl-2-mercaptomethyl-4- (2, 2, 2-trifluoroethoxy) pyridine hydrochloride in the form of pale yellow crystals.
NMR J (DMSO-df): 2.27 (3N, s), 4.16 (2H, brs), 5.21 (21, KB, J 9 Hz) -,
7.62 (1H, d, J 7Hz), 8.73 (1H, g, J 7Hz).
Example 9. A mixture of 140 ml of 3-methyl-2-mercaptomethyl-4- (2,2,2-trifluoroethoxy) pyridine hydrochloride and 76 mg of 2-chlorobenzimidazole in methanol (5 ml)
heated at AO-ZO C for 90 h with stirring.
To the reaction solution are added 20 ml of saturated sodium bicarbonate, extracted with ethyl acetate, washed with water and dried over magnesium sulfate.
After evaporation of the solvent, the resulting residue is passed through a column of 30 g of silica gel, eluting with ethnyl acetate, and concentrated.
The concentrate is dissolved in a small amount of ethyl acetate, and then recrystallized from hexane to give 87 mg of 2-Cz-methyl-4- (2,2,2-trifluoro-ethoxy) pyrid-2-yl methylthiobenzimidazole as a white powder. m.p. ISO-ISI C.
Experimental technique. Seven-week-old male Sprague-Dawley rats were not allowed to eat for 24 hours. After this, the test compounds were injected into the animals into the stomach using a stomach probe.
After 30 minutes, 1 ml of 100% ethanol was orally administered. 60 minutes after the administration, the animals were sacrificed with carbon dioxide gas. In killed animals, the stomach was removed from the bottom. part of the esophagus and dvemadtsadoperstnoy. The esophagus was clamped, 10 ml of a 1% formalin solution was injected into the stomach through the duodenum, after which the duodenum was also clamped and the entire stomach was immersed in a 1% formalin solution. After 15 minutes, the stomachs were opened along a larger curve. The area of wounds in the gastric mucosa was determined using an anatomical microscope with a square grid in the ocular, (10). Determine the total part number for each animal and calculate the average for each group. The rate of inhibition was determined by the difference between the mean values of each of the test and control groups. Test compounds were suspended in a 5% solution of gum arabic and administered in an amount of 2 ml / kg.

权利要求:
Claims (1)
[1]
Invention Formula
The method of producing pyridine derivatives of the general formula
g, O-
2 1 n D
14JO-S-CH, 4J N / D N
N (A) n 0
Where
R, is hydrogen, methoxy or
trifluoromethyl;
RJ and Rj are each independently hydrogen or methyl R are fluorinated C-Cj-alkyl;
n "O or 1,
characterized in that the compound of formula
G-1x,
N t
1 N
where X, - SH,
subjected to interaction with the compound of the formula
P
R.-vA.R,
h
. and - 3
where RI - RI have the indicated values X and Xj - one SH and the other one is halogen,
and, if necessary, the resulting compound is subjected to acid oxidation.
Table 1
RS "4 m.p.,
The compound of formula (VI)
WITH
Nuclear Magnetic Resonance Spectrum (CDCl1): 2.22 (ZN, s), 2.50 (ZN, s), 4.63 (2H, t, J 12 Hz),
6.2A (1H, tt, J 6.51 Hz), 6.87 (1H, d, J 7.5 Hz), 8.15 (1H, d, J 7.5 Hz)
The compound of formula (VIII)
N N N N
sn
H
sn,
H N N
SECSGs
SN SGGSRz
CH, CFaCb H
CH CF CF-jH
CH (CFT,) CF3
CH, (CF) H
spectrum (CDCl1): 2.08 (3N, s), 4.50 (2H, tt, J 12.1 Hz), 4.66, s), 6.67 (1H, d, J 6 Hz), 8 , 33 (1H, d, J 6 Hz).
spectrum (CDCl1): 2.10 (2H, s), 4.50 (1H, br), 4.54 (2H, t, J 2 Hz), 4.68 (2H, s), 6.11 ( 1H, tt, J 6.51 Hz), 6.71 (1H, d, 6 Hz), 8.32 (1H, d, J 6 Hz).
NMR (2H NMR
1 I in. -Iiji / j f t4yii
J 6 Hz), 8.32 (1H, d, J 6 Hz).
Table 4
Table
Table
Oil nista liquid 93,5-94,0
Oil nista ti liquid
87-89
88-89
98-99
67-68
Oily
Oily
171507211, 8
Table 6
NMR spectrum (CDCl1): 4.35 (s), 4.39 (t, t, J - 1.5 and 12 Hz), 5.98 (1H, t, t, J - 52.5 and 4 Hz) , 6.81 (W, d, d J - 2 and 6 Hz), 6.95 (1H, d, J - 2 Hz, 7.1-7.3 (2H, m), 7.4-7, 7 (2H, m), 8.50 1H, d, J 6 Hz). 1 / 4H, h | 0 (water of crystallization).
Note, d-c decomposition.
Table 7
0-r
R, 4iJO - s-CH,
r, (oV
The compound described in Example 23 of U.S. Patent No. 4,255,431 (unaccepted application of Japan No. 141783, 1979).
The joint described in example 3 of the OHP patent fP 4472409 (unaccepted application of Japan No. 135881, 1983).
The groups consisted of (S rats} to determine the average lethal dose of ClD s o) each of the tested compounds was administered in an amount of 1,3,10 and 30 ig / kg ..
Table 8
faces

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同族专利:

公开号 | 公开日

NL930109I2|1997-02-03|

EP0174726A1|1986-03-19|

ZA856117B|1986-04-30|

DK356485D0|1985-08-06|

UA7140A1|1995-06-30|

DE19975017I2|2009-08-06|

BG60415B2|1995-02-28|

IE851976L|1986-02-16|

DK356485A|1986-02-17|

DE3569736D1|1989-06-01|

ES8607288A1|1986-05-16|

HUT39444A|1986-09-29|

DK171340B1|1996-09-16|

ES546152A0|1986-05-16|

SG103291G|1993-02-19|

NO163131B|1990-01-02|

AU570130B2|1988-03-03|

US4628098A|1986-12-09|

NO1995002I1|1995-03-31|

PH20946A|1987-06-10|

KR870002125A|1987-03-30|

EP0174726B1|1989-04-26|

KR920002128B1|1992-03-12|

NL930109I1|1993-10-18|

NO163131C|1994-10-24|

NO853226L|1986-02-17|

MX9203043A|1992-07-01|

AU4589585A|1986-02-20|

HU195210B|1988-04-28|

IE58363B1|1993-09-08|

JPH0244473B2|1990-10-04|

DE19975020I2|2009-08-06|

HK4792A|1992-01-17|

CA1255314A|1989-06-06|

US4689333A|1987-08-25|

JPS6150978A|1986-03-13|

GR851981B|1985-12-16|

引用文献:

公开号 | 申请日 | 公开日 | 申请人 | 专利标题

SE416649B|1974-05-16|1981-01-26|Haessle Ab|PROCEDURE FOR THE PREPARATION OF SUBSTANCES WHICH PREVENT Gastric acid secretion|

SE7804231L|1978-04-14|1979-10-15|Haessle Ab|Gastric acid secretion|

US4359465A|1980-07-28|1982-11-16|The Upjohn Company|Methods for treating gastrointestinal inflammation|

IL66340A|1981-08-13|1986-08-31|Haessle Ab|Pharmaceutical compositions comprising pyridylmethyl-thiobenzimidazole derivatives,certain such novel derivatives and their preparation|

US4472409A|1981-11-05|1984-09-18|Byk Gulden Lomberg Chemische Fabrik Gesellschaft Mit Beschrankter Haftung|2-Pyridylmethyl thiobenzimidazoles with gastric acid secretion inhibiting effects|

SE8300736D0|1983-02-11|1983-02-11|Haessle Ab|NOVEL PHARMACOLOGICALLY ACTIVE COMPOUNDS|

IL71664A|1983-05-03|1987-11-30|Byk Gulden Lomberg Chem Fab|Fluoroalkoxy compounds,process for their preparation and pharmaceutical compositions containing the same|

US4575554A|1983-12-05|1986-03-11|The Upjohn Company|Substituted 2-pyridylmethylthio- and sulfinyl-benzimidazoles as gastric antisecretory agents|

IL75400A|1984-06-16|1988-10-31|Byk Gulden Lomberg Chem Fab|Dialkoxypyridine methylbenzimidazoles,processes for the preparation thereof and pharmaceutical compositions containing the same|

GB8417171D0|1984-07-05|1984-08-08|Beecham Group Plc|Compounds|

SE8404065D0|1984-08-10|1984-08-10|Haessle Ab|NOVEL BIOLOGICALLY ACTIVE COMPOUNDS|EP0174717B1|1984-07-06|1992-01-22|FISONS plc|Benzimidazoles, and their production formulation and use as gastric acid secretion inhibitors|

CA1276017C|1986-02-13|1990-11-06|Takeda Chemical Industries, Ltd.|Sulfenamide derivatives and their production|

US5433959A|1986-02-13|1995-07-18|Takeda Chemical Industries, Ltd.|Stabilized pharmaceutical composition|

US6749864B2|1986-02-13|2004-06-15|Takeda Chemical Industries, Ltd.|Stabilized pharmaceutical composition|

CA1327010C|1986-02-13|1994-02-15|Tadashi Makino|Stabilized solid pharmaceutical composition containing antiulcer benzimidazole compound and its production|

DK171989B1|1987-08-04|1997-09-08|Takeda Chemical Industries Ltd|Process for the preparation of 2-benzimidazoles|

WO1989011479A1|1988-05-25|1989-11-30|Byk Gulden Lomberg Chemische Fabrik Gmbh|New fluoralkoxy compounds|

US5223515A|1988-08-18|1993-06-29|Takeda Chemical Industries, Ltd.|Injectable solution containing a pyridyl methylsulfinylbenzimidazole|

JP2536173B2|1988-08-18|1996-09-18|武田薬品工業株式会社|Injection|

AT391693B|1988-11-15|1990-11-12|Cl Pharma|METHOD FOR PRODUCING 3-5-DIMETHYL-4METHOXYPYRIDINE DERIVATIVES AND NEW INTERMEDIATE PRODUCT THEREFOR|

SE8804628A|1988-12-22|1988-12-22|

IE64199B1|1988-12-22|1995-07-12|Haessle Ab|Compound with gastric acid inhibitory effect and process for its preparation|

SE8804629D0|1988-12-22|1988-12-22|Ab Haessle|NEW THERAPEUTICALLY ACTIVE COMPOUNDS|

DE69014141T2|1989-02-10|1995-05-24|Takeda Chemical Industries Ltd|Use of benzimidazole derivatives as antibacterial agents.|

US4965269A|1989-12-20|1990-10-23|Ab Hassle|Therapeutically active chloro substituted benzimidazoles|

US5274099A|1989-12-20|1993-12-28|Aktiebolaget Hassle|Therapeutically active fluoro substituted benzimidazoles|

US5049674A|1989-12-20|1991-09-17|Aktiebolaget Hassle|Therapeutically active fluoro substituted benzimidazoles|

US5312824A|1990-10-17|1994-05-17|Takeda Chemical Industries, Ltd.|Certain 2-[-methylthio or methylsulfinyl-5-benzimidazoles useful for treating peptic ulcers|

TW209174B|1991-04-19|1993-07-11|Takeda Pharm Industry Co Ltd|

WO1993006097A1|1991-09-20|1993-04-01|Merck & Co., Inc.|Novel process for the preparation of anti-ulcer agents|

ES2036948B1|1991-11-21|1994-09-01|Genesis Para La Investigacion|PROCEDURE FOR OBTAINING COMPOUNDS DERIVED FROM PIRIDINE.|

EP0649305A1|1992-07-08|1995-04-26|Monsanto Company|Benzimidazoles for alleviating stomach ulcers in swine|

KR100258423B1|1992-07-28|2000-07-01|클래스 빌헬름슨|Injection and injection kit containing omeprazole and its analogs|

CA2156258A1|1993-02-17|1994-09-01|Bernhard Kohl|Substituted heteroarylalkylthiopyridines for controlling helicobacter bacteria|

ES2060541B1|1993-02-26|1995-11-16|Vinas Lab|NEW PROCEDURE FOR THE SYNTHESIS OF A DERIVATIVE OF 2-BENCIMIDAZOLE, AND NEW INTERMEDIATE PRODUCTS OBTAINED WITH THE SAME.|

ES2063705B1|1993-06-14|1995-07-16|S A L V A T Lab Sa|INTERMEDIATE FOR THE SYNTHESIS OF LANSOPRAZOLE AND ITS PROCEDURE FOR OBTAINING.|

TW280770B|1993-10-15|1996-07-11|Takeda Pharm Industry Co Ltd|

US5502195A|1993-11-04|1996-03-26|Slemon; Clarke|Sulfoxide-carboxylate intermediates of omeprazole and lansoprazole|

US5374730A|1993-11-04|1994-12-20|Torcan Chemical Ltd.|Preparation of omeprazole and lansoprazole|

CN1048980C|1994-03-29|2000-02-02|广东汕头鮀滨化学药业总公司|Preparation of pyridine derivative and application thereof|

SE9402431D0|1994-07-08|1994-07-08|Astra Ab|New tablet formulation|

GB9423968D0|1994-11-28|1995-01-11|Astra Ab|Resolution|

SE9500422D0|1995-02-06|1995-02-06|Astra Ab|New oral pharmaceutical dosage forms|

SE9500478D0|1995-02-09|1995-02-09|Astra Ab|New pharmaceutical formulation and process|

US5708017A|1995-04-04|1998-01-13|Merck & Co., Inc.|Stable, ready-to-use pharmaceutical paste composition containing proton pump inhibitors|

US5824339A|1995-09-08|1998-10-20|Takeda Chemical Industries, Ltd|Effervescent composition and its production|

DE69634160T2|1995-09-21|2005-12-22|Pharma Pass Ii Llc, Irvine|An acid-labile omeprazole-containing drug composition and process for its preparation|

SE521100C2|1995-12-15|2003-09-30|Astra Ab|Process for the preparation of a benzimidazole compound|

US5840737A|1996-01-04|1998-11-24|The Curators Of The University Of Missouri|Omeprazole solution and method for using same|

US6489346B1|1996-01-04|2002-12-03|The Curators Of The University Of Missouri|Substituted benzimidazole dosage forms and method of using same|

US6699885B2|1996-01-04|2004-03-02|The Curators Of The University Of Missouri|Substituted benzimidazole dosage forms and methods of using same|

US6645988B2|1996-01-04|2003-11-11|Curators Of The University Of Missouri|Substituted benzimidazole dosage forms and method of using same|

SE9600070D0|1996-01-08|1996-01-08|Astra Ab|New oral pharmaceutical dosage forms|

US8071128B2|1996-06-14|2011-12-06|Kyowa Hakko Kirin Co., Ltd.|Intrabuccally rapidly disintegrating tablet and a production method of the tablets|

US6599927B2|1996-10-11|2003-07-29|Astrazeneca Ab|Use of an H+, K+-ATPase inhibitor in the treatment of Widal's Syndrome|

TW385306B|1996-11-14|2000-03-21|Takeda Chemical Industries Ltd|Method for producing crystals of benzimidazole derivatives|

WO1998054172A1|1997-05-30|1998-12-03|Dr. Reddy's Research Foundation|Novel benzimidazole derivatives as antiulcer agents, process for their preparation and pharmaceutical compositions containing them|

SI1003554T1|1997-07-25|2005-04-30|Altana Pharma Ag|Proton pump inhibitor in therapeutic combination with antibacterial substances|

SE9704870D0|1997-12-22|1997-12-22|Astra Ab|New pharmaceutical formulation I|

US20040224989A1|1999-01-29|2004-11-11|Barberich Timothy J.|S-lansoprazole compositions and methods|

ES2559766T3|1998-05-18|2016-02-15|Takeda Pharmaceutical Company Limited|Disintegrable tablets in the mouth|

ZA9810765B|1998-05-28|1999-08-06|Ranbaxy Lab Ltd|Stable oral pharmaceutical composition containing a substituted pyridylsulfinyl benzimidazole.|

WO2000000474A1|1998-06-26|2000-01-06|Russinsky Limited|Pyridine building blocks as intermediates in the synthesis of pharmaceutically active compounds|

SI20019A|1998-07-13|2000-02-29|LEK, tovarna farmacevtskih in kemičnih izdelkov, d.d.|An improved process for synthesis of 5-methoxy-2-/methyl/ sulphynyl-1h-benzimidazol|

JP2002521336A|1998-07-22|2002-07-16|セプラコール，インク．|Pharmaceutical compositions containing hydroxylansoprazole and uses thereof|

US6093734A|1998-08-10|2000-07-25|Partnership Of Michael E. Garst, George Sachs, And Jai Moo Shin|Prodrugs of proton pump inhibitors|

UA67788C2|1998-08-10|2004-07-15|Ріджентс Оф Зе Юніверсіті Оф Каліфорніа|Prodrugs of the proton pump inhibitorsand pharmaceutical composition based thereon|

DK1105105T3|1998-08-12|2006-07-17|Altana Pharma Ag|Oral administration form for pyridin-2-ylmethylsulfinyl-1H-benzimidazoles|

DE19843413C1|1998-08-18|2000-03-30|Byk Gulden Lomberg Chem Fab|New salt form of pantoprazole|

JP3926936B2|1998-11-16|2007-06-06|エーザイ・アール・アンド・ディー・マネジメント株式会社|Sulfoxide derivative / acetone complex and production method thereof|

US7732404B2|1999-12-30|2010-06-08|Dexcel Ltd|Pro-nanodispersion for the delivery of cyclosporin|

US6852739B1|1999-02-26|2005-02-08|Nitromed Inc.|Methods using proton pump inhibitors and nitric oxide donors|

US6245913B1|1999-06-30|2001-06-12|Wockhardt Europe Limited|Synthetic procedure for 5-methoxy-2-[-methylthio]-IH-benzimidazole hydrochloride and its conversion to omeprazole|

US6608092B1|1999-06-30|2003-08-19|Takeda Chemical Industries, Ltd.|Crystals of benzimidazole compounds|

US6369087B1|1999-08-26|2002-04-09|Robert R. Whittle|Alkoxy substituted benzimidazole compounds, pharmaceutical preparations containing the same, and methods of using the same|

US6316020B1|1999-08-26|2001-11-13|Robert R. Whittle|Pharmaceutical formulations|

US6262086B1|1999-08-26|2001-07-17|Robert R. Whittle|Pharmaceutical unit dosage form|

US6326384B1|1999-08-26|2001-12-04|Robert R. Whittle|Dry blend pharmaceutical unit dosage form|

US6780880B1|1999-08-26|2004-08-24|Robert R. Whittle|FT-Raman spectroscopic measurement|

US6312712B1|1999-08-26|2001-11-06|Robert R. Whittle|Method of improving bioavailability|

US6268385B1|1999-08-26|2001-07-31|Robert R. Whittle|Dry blend pharmaceutical formulations|

US6262085B1|1999-08-26|2001-07-17|Robert R. Whittle|Alkoxy substituted Benzimidazole compounds, pharmaceutical preparations containing the same, and methods of using the same|

US6312723B1|1999-08-26|2001-11-06|Robert R. Whittle|Pharmaceutical unit dosage form|

US6228400B1|1999-09-28|2001-05-08|Carlsbad Technology, Inc.|Orally administered pharmaceutical formulations of benzimidazole derivatives and the method of preparing the same|

KR100359256B1|1999-10-06|2002-11-04|한미약품공업 주식회사|Improved method of preparing lansoprazole|

SE9903831D0|1999-10-22|1999-10-22|Astra Ab|Formulation of substituted benzimidazoles|

US20030180352A1|1999-11-23|2003-09-25|Patel Mahesh V.|Solid carriers for improved delivery of active ingredients in pharmaceutical compositions|

US20060034937A1|1999-11-23|2006-02-16|Mahesh Patel|Solid carriers for improved delivery of active ingredients in pharmaceutical compositions|

SE0000774D0|2000-03-08|2000-03-08|Astrazeneca Ab|New formulation|

ES2171116B1|2000-04-14|2003-08-01|Esteve Quimica Sa|PROCEDURE FOR OBTAINING DERIVATIVES OFMETAL) UNCLE) BENCIMIDAZOL.|

CN100562318C|2000-05-15|2009-11-25|武田药品工业株式会社|Crystalline preparation method|

JP5412023B2|2000-08-04|2014-02-12|武田薬品工業株式会社|Salts of benzimidazole compounds and uses thereof|

US6544556B1|2000-09-11|2003-04-08|Andrx Corporation|Pharmaceutical formulations containing a non-steroidal antiinflammatory drug and a proton pump inhibitor|

US20020064555A1|2000-09-29|2002-05-30|Dan Cullen|Proton pump inhibitor formulation|

KR20100002278A|2000-12-01|2010-01-06|다케다 야쿠힌 고교 가부시키가이샤|Crystal of - or -lansoprazole|

WO2002045686A2|2000-12-07|2002-06-13|Altana Pharma Ag|Pharmaceutical paste comprising an acid-labile active ingredient|

ES2403238T3|2000-12-07|2013-05-16|Takeda Gmbh|Pharmaceutical preparation in the form of a suspension comprising an active ingredient labile in acidic medium|

PT1341528E|2000-12-07|2012-03-20|Nycomed Gmbh|Rapidly disintegrating tablet comprising an acid-labile active ingredient|

KR100430575B1|2001-02-21|2004-05-10|주식회사 씨트리|Method of Preparing Lansoprazole and Its Intermediate|

US6645946B1|2001-03-27|2003-11-11|Pro-Pharmaceuticals, Inc.|Delivery of a therapeutic agent in a formulation for reduced toxicity|

SE0101379D0|2001-04-18|2001-04-18|Diabact Ab|Composition that inhibits gastric acid secretion|

US8206741B2|2001-06-01|2012-06-26|Pozen Inc.|Pharmaceutical compositions for the coordinated delivery of NSAIDs|

CA2523218A1|2003-04-22|2004-11-04|Dr. Reddy's Laboratories Limited|Oral pharmaceutical formulations of acid-labile active ingredients and process for making same|

SE0102993D0|2001-09-07|2001-09-07|Astrazeneca Ab|New self emulsifying drug delivery system|

AU2002332178B2|2001-09-18|2005-12-08|Zeria Pharmaceutical Co., Ltd.|Benzimidazole derivatives|

EP1437352A4|2001-09-25|2004-12-08|Takeda Chemical Industries Ltd|Benzimidazole compound, process for producing the same, and use thereof|

US9358214B2|2001-10-04|2016-06-07|Adare Pharmaceuticals, Inc.|Timed, sustained release systems for propranolol|

US8101209B2|2001-10-09|2012-01-24|Flamel Technologies|Microparticulate oral galenical form for the delayed and controlled release of pharmaceutical active principles|

DK1459737T3|2001-10-17|2013-01-02|Takeda Pharmaceutical|Granules containing acid unstable chemical in large quantity|

SE0104295D0|2001-12-18|2001-12-18|Astrazeneca Ab|New process|

DE60325709D1|2002-04-09|2009-02-26|Flamel Tech Sa|ORAL AQUEOUS SUSPENSION CONTAINING MICRO CAPSULES FOR THE CONTROLLED RELEASE OF ACTIVE SUBSTANCES|

IL164221D0|2002-04-09|2005-12-18|Flamel Tech Sa|Oral pharmaceutical formulation in the form of aqueous suspension of microcapsules for modified release of amoxicillim|

US20030228363A1|2002-06-07|2003-12-11|Patel Mahendra R.|Stabilized pharmaceutical compositons containing benzimidazole compounds|

KR100873419B1|2002-06-18|2008-12-11|페어차일드코리아반도체 주식회사|Power Semiconductor device having high breakdown voltage, low on-resistance and small switching loss|

AT323695T|2002-07-19|2006-05-15|Winston Pharmaceuticals Llc|BENZIMIDAZOLE DERIVATIVES AND THEIR USE AS PRODRUGS FOR PROTONAL PUMP INHIBITORS|

TW200410955A|2002-07-29|2004-07-01|Altana Pharma Ag|Novel salt of -PANTOPRAZOLE|

CA2493618A1|2002-08-01|2004-02-12|Nitromed, Inc.|Nitrosated proton pump inhibitors, compositions and methods of use|

DE60316791T2|2002-08-21|2008-07-24|Teva Pharmaceutical Industries Ltd.|PROCESS FOR PURIFYING LANZOPRAZOLE|

CN1674916A|2002-08-30|2005-09-28|奥坦纳医药公司|The use of the combination of ciclesonide and antihistamines for the treatment of allergic rhinitis|

SE0203065D0|2002-10-16|2002-10-16|Diabact Ab|Gastric acid secretion inhibiting composition|

MY148805A|2002-10-16|2013-05-31|Takeda Pharmaceutical|Controlled release preparation|

EP1552833B1|2002-10-16|2016-12-28|Takeda Pharmaceutical Company Limited|Process for producing an amorphous optically active isomer of lansoprazole|

KR20050075424A|2002-11-18|2005-07-20|테바 파마슈티컬 인더스트리즈 리미티드|Stable lansoprazole containing more than 500 ppm, up to about 3,000 ppm water and more than 200 ppm, up to about 5,000 ppm alcohol|

EP1743893A1|2002-11-18|2007-01-17|Teva Pharmaceutical Industries Ltd.|Stable lansoprazole containing more than 500 ppm, up to about 3,000 ppm water and more than 200 ppm, up to about 5,000 ppm alcohol|

DE10254167A1|2002-11-20|2004-06-09|Icon Genetics Ag|Process for the control of cellular processes in plants|

PL375818A1|2002-12-06|2005-12-12|Altana Pharma Ag|Process for preparing optically pure active compounds|

AR042278A1|2002-12-06|2005-06-15|Altana Pharma Ag|A PROCEDURE FOR THE PREPARATION OF- PANTOPRAZOL|

AU2003303240A1|2002-12-19|2004-07-14|Eva Pharmaceutical Industries Ltd.|Solid states of pantoprazole sodium, processes for preparing them and processes for preparing known pantoprazole sodium hydrates|

US8367111B2|2002-12-31|2013-02-05|Aptalis Pharmatech, Inc.|Extended release dosage forms of propranolol hydrochloride|

CA2515130A1|2003-02-05|2004-08-26|Teva Pharmaceutical Industries Ltd.|Method of stabilizing lansoprazole|

US20050220870A1|2003-02-20|2005-10-06|Bonnie Hepburn|Novel formulation, omeprazole antacid complex-immediate release for rapid and sustained suppression of gastric acid|

ES2245277T1|2003-03-12|2006-01-01|Teva Pharmaceutical Industries Limited|SOLIDOS CRYSTALS AND AMORPHES OF PANTOPRAZOL AND PROCEDURES FOR THEIR PREPARATION.|

CA2518780C|2003-03-12|2014-05-13|Takeda Pharmaceutical Company Limited|Drug composition having active ingredient adhered at high concentration to spherical core|

JP4355703B2|2003-03-13|2009-11-04|エーザイ・アール・アンド・ディー・マネジメント株式会社|Preventive or therapeutic agent for bruxism|

CL2004000983A1|2003-05-08|2005-03-04|Altana Pharma Ag|ORAL PHARMACEUTICAL COMPOSITION IN THE FORM OF A TABLET THAT INCLUDES DIHYDRATED MAGNETIC PANTOPRAZOL, WHERE THE TABLET FORM IS COMPOSED BY A NUCLEUS, A MIDDLE COAT AND AN OUTER LAYER; AND USE OF PHARMACEUTICAL COMPOSITION IN ULCERAS AND|

PE20050150A1|2003-05-08|2005-03-22|Altana Pharma Ag|A DOSAGE FORM CONTAINING-PANTOPRAZOLE AS AN ACTIVE INGREDIENT|

EP1615913A2|2003-06-10|2006-01-18|Teva Pharmaceutical Industries Limited|Process for preparing 2-methyl sulfinyl-substituted benzimidazoles and novel chlorinated derivatives of pantoprazole|

EP2112920B1|2003-06-26|2018-07-25|Intellipharmaceutics Corp.|Proton pump-inhibitor-containing capsules which comprise subunits differently structured for a delayed release of the active ingredient|

PL379542A1|2003-07-15|2006-10-02|Allergan, Inc.|Process for preparing isomerically pure prodrugs of proton pump inhibitors|

US8993599B2|2003-07-18|2015-03-31|Santarus, Inc.|Pharmaceutical formulations useful for inhibiting acid secretion and methods for making and using them|

AU2004268383A1|2003-09-03|2005-03-10|Agi Therapeutics Limited|Proton pump inhibitor formulations, and methods of preparing and using such formulations|

US20050075371A1|2003-10-03|2005-04-07|Allergan, Inc.|Methods and compositions for the oral administration of prodrugs of proton pump inhibitors|

US20060241037A1|2003-10-03|2006-10-26|Allergan Inc.|Compositions comprising trefoil factor family peptides and/or mucoadhesives and proton pump ihhibitor prodrugs|

US20050249806A1|2004-02-10|2005-11-10|Santarus, Inc.|Combination of proton pump inhibitor, buffering agent, and nonsteroidal anti-inflammatory drug|

GB0403165D0|2004-02-12|2004-03-17|Ct|Novel uses for proton pump inhibitors|

AU2005216863A1|2004-02-18|2005-09-09|Allergan, Inc.|Methods and compositions for the intravenous administration of compounds related to proton pump inhibitors|

JP2007523163A|2004-02-18|2007-08-16|アラーガン、インコーポレイテッド|Methods and compositions for the administration of prodrugs of proton pump inhibitors|

US20050214372A1|2004-03-03|2005-09-29|Simona Di Capua|Stable pharmaceutical composition comprising an acid labile drug|

CA2561700A1|2004-04-16|2005-12-15|Santarus, Inc.|Combination of proton pump inhibitor, buffering agent, and prokinetic agent|

EP1742946A1|2004-04-28|2007-01-17|Altana Pharma AG|Dialkoxy-imidazopyridines derivatives|

US8815916B2|2004-05-25|2014-08-26|Santarus, Inc.|Pharmaceutical formulations useful for inhibiting acid secretion and methods for making and using them|

US8906940B2|2004-05-25|2014-12-09|Santarus, Inc.|Pharmaceutical formulations useful for inhibiting acid secretion and methods for making and using them|

JP5563735B2|2004-06-16|2014-07-30|タケダファーマシューティカルズユー．エス．エー．インコーポレイティド|PPI multiple dosage form|

US8394409B2|2004-07-01|2013-03-12|Intellipharmaceutics Corp.|Controlled extended drug release technology|

US20060024362A1|2004-07-29|2006-02-02|Pawan Seth|Composition comprising a benzimidazole and process for its manufacture|

US10624858B2|2004-08-23|2020-04-21|Intellipharmaceutics Corp|Controlled release composition using transition coating, and method of preparing same|

CA2579665C|2004-09-13|2014-03-18|Takeda Pharmaceutical Company Limited|Method and apparatus for producing oxidized compound|

US8747895B2|2004-09-13|2014-06-10|Aptalis Pharmatech, Inc.|Orally disintegrating tablets of atomoxetine|

US9884014B2|2004-10-12|2018-02-06|Adare Pharmaceuticals, Inc.|Taste-masked pharmaceutical compositions|

NZ589750A|2004-10-21|2012-07-27|Aptalis Pharmatech Inc|Taste-masked pharmaceutical compositions with gastrosoluble pore-formers|

US20060105038A1|2004-11-12|2006-05-18|Eurand Pharmaceuticals Limited|Taste-masked pharmaceutical compositions prepared by coacervation|

WO2006053383A1|2004-11-22|2006-05-26|Anadis Ltd|Bioactive compositions|

EP1681056A1|2005-01-14|2006-07-19|Krka Tovarna Zdravil, D.D., Novo Mesto|Process for preparing lansoprazole|

WO2006090845A1|2005-02-25|2006-08-31|Takeda Pharmaceutical Company Limited|Method for producing granules|

KR100771659B1|2005-03-23|2007-10-30|주식회사 카이로제닉스|Method of Preparing Pantoprazole and Its Intermediate|

US9161918B2|2005-05-02|2015-10-20|Adare Pharmaceuticals, Inc.|Timed, pulsatile release systems|

US7981908B2|2005-05-11|2011-07-19|Vecta, Ltd.|Compositions and methods for inhibiting gastric acid secretion|

US7803817B2|2005-05-11|2010-09-28|Vecta, Ltd.|Composition and methods for inhibiting gastric acid secretion|

US20090036406A1|2005-06-13|2009-02-05|Takeda Pharmaceutical Company Limited|Injection|

US7601737B2|2005-07-26|2009-10-13|Nycomed Gmbh|Isotopically substituted proton pump inhibitors|

CA2624179A1|2005-10-06|2007-04-12|Auspex Pharmaceuticals, Inc.|Deuterated inhibitors of gastric h+, k+-atpase with enhanced therapeutic properties|

GB0525710D0|2005-12-17|2006-01-25|Pliva Hrvatska D O O|An improved process for preparing of substituted 2-benzimidazolesulfoxide compounds|

US10064828B1|2005-12-23|2018-09-04|Intellipharmaceutics Corp.|Pulsed extended-pulsed and extended-pulsed pulsed drug delivery systems|

US8486450B2|2005-12-28|2013-07-16|Takeda Pharmaceutical Company Limited|Method of producing solid preparation disintegrating in the oral cavity|

EP1967183A4|2005-12-28|2011-02-23|Takeda Pharmaceutical|Controlled release solid preparation|

PL2003130T3|2006-03-10|2012-04-30|Link Genomics Inc|Novel pyridine derivative having anti-helicobacter pylori activity|

EP2007360B1|2006-04-03|2014-11-26|Isa Odidi|Controlled release delivery device comprising an organosol coat|

US10960077B2|2006-05-12|2021-03-30|Intellipharmaceutics Corp.|Abuse and alcohol resistant drug composition|

JP2009538901A|2006-06-01|2009-11-12|デクセルファーマテクノロジーズエルティーディー．|Dual unit pharmaceutical formulation|

US7863330B2|2006-06-14|2011-01-04|Rottapharm S.P.A.|Deloxiglumide and proton pump inhibitor combination in the treatment of gastrointestinal disorders|

KR101489370B1|2006-07-25|2015-02-03|벡타 리미티드|Compositions and methods for inhibiting gastric acid secretion using derivatives of small dicarboxylic acids in combination with ppi|

WO2008036201A1|2006-09-19|2008-03-27|Alevium Pharmaceuticals, Inc.|Prodrugs of proton pump inhibitors including the 1h-imidazo[4,5-b] pyridine moiety|

US8129536B2|2006-09-22|2012-03-06|Orchid Chemicals & Pharmaceuticals Limited|Method for the purification of lansoprazole|

CA2665226C|2006-10-05|2014-05-13|Santarus, Inc.|Novel formulations of proton pump inhibitors and methods of using these formulations|

AU2007317561A1|2006-10-27|2008-05-15|The Curators Of The University Of Missouri|Compositions comprising at least one acid labile proton pump inhibiting agents, optionally other pharmaceutically active agents and methods of using same|

ZA200904573B|2006-12-22|2010-09-29|Ironwood Pharmaceuticals Inc|Compositions comprising bile acid sequestrants for treating esophageal disorders|

US9486446B2|2006-12-28|2016-11-08|Takeda Pharmaceutical Company Limited|Orally disintegrating solid preparation|

WO2008087665A2|2007-01-18|2008-07-24|Matrix Laboratories Ltd|Process for preparation of lansoprazole|

US20080194307A1|2007-02-13|2008-08-14|Jeff Sanger|Sports-based game of chance|

TW200840574A|2007-04-02|2008-10-16|Univ Nat Taiwan|The pharmaceutical component for treating hearing loss disease|

WO2009010937A1|2007-07-17|2009-01-22|Ranbaxy Laboratories Limited|Process for the preparation op pantoprazole sodium and pantoprazole sodium sesquihydrate|

JP5629581B2|2007-10-12|2014-11-19|タケダファーマシューティカルズユー．エス．エー．インコーポレイティド|Method for treating digestive disorders independent of food intake|

US20100280077A1|2007-12-18|2010-11-04|Watson Pharma Private Limited|Process for Preparation of Stable Amorphous R-Lansoprazole|

EP2573082A1|2007-12-31|2013-03-27|Takeda Pharmaceutical Company Limited|Crystalline solvated forms of-2-[[[3-methyl-4--2-pyridinyl]methyl]sulfinyl]-1h-benzimidazole|

EP2252274A4|2008-02-20|2011-05-11|Univ Missouri|Composition comprising a combination of omeprazole and lansoprazole, and a buffering agent, and methods of using same|

US20090227633A1|2008-03-04|2009-09-10|Bassam Damaj|Methods to inhibit tumor cell growth by using proton pump inhibitors|

MX2010009641A|2008-03-10|2010-09-22|Takeda Pharmaceutical|Crystal of benzimidazole compound.|

US20090263475A1|2008-04-21|2009-10-22|Nagaraju Manne|Dexlansoprazole compositions|

US8362042B2|2008-05-14|2013-01-29|Watson Pharma Private Limited|Stable R-lansoprazole amine salt and a process for preparing the same|

CN102209529A|2008-09-09|2011-10-05|阿斯利康有限公司|Method for delivering a pharmaceutical composition to patient in need thereof|

WO2010039885A2|2008-09-30|2010-04-08|Teva Pharmaceutical Industries Ltd.|Crystalline forms of dexlansoprazole|

US20100093747A1|2008-10-10|2010-04-15|Erica Brook Goodhew|Method of inducing negative chemotaxis|

US20100173882A1|2009-01-08|2010-07-08|Lipocine, Inc.|Steroidal Compositions|

WO2010122583A2|2009-04-24|2010-10-28|Rubicon Research Private Limited|Oral pharmaceutical compositions of acid labile substances|

WO2010134099A1|2009-05-21|2010-11-25|Cadila Healthcare Limited|One pot process for preparing omeprazole and related compounds|

WO2011004387A2|2009-06-18|2011-01-13|Matrix Laboratories Ltd|Process for the preparation of dexlansoprazole polymorphic forms|

AU2010263304A1|2009-06-25|2012-02-02|Astrazeneca Ab|Method for treating a patient at risk for developing an NSAID-associated ulcer|

AU2010325746B2|2009-12-02|2016-02-25|Adare Pharmaceuticals S.R.L.|Fexofenadine microcapsules and compositions containing them|

WO2011080501A2|2009-12-29|2011-07-07|Orexo Ab|New pharmaceutical dosage form for the treatment of gastric acid-related disorders|

WO2011080500A2|2009-12-29|2011-07-07|Orexo Ab|New pharmaceutical dosage form for the treatment of gastric acid-related disorders|

WO2011080502A2|2009-12-29|2011-07-07|Orexo Ab|New pharmaceutical dosage form for the treatment of gastric acid-related disorders|

TW201127375A|2010-01-08|2011-08-16|Eurand Inc|Taste masked topiramate composition and an orally disintegrating tablet comprising the same|

US20110189271A1|2010-02-02|2011-08-04|Vishal Lad|Pharmaceutical formulations of acid-labile drugs|

WO2011138797A2|2010-05-04|2011-11-10|Cadila Healthcare Limited|Delayed release oral disintegrating pharmaceutical compositions of lansoprazole|

WO2012001705A2|2010-06-29|2012-01-05|Cadila Healthcare Limited|Pharmaceutical compositions of -lansoprazole|

WO2012027331A1|2010-08-27|2012-03-01|Ironwood Pharmaceuticals, Inc.|Compositions and methods for treating or preventing metabolic syndrome and related diseases and disorders|

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MY180677A|2010-12-03|2020-12-05|Takeda Pharmaceuticals Co|Orally disintegrating tablet|

US20120148675A1|2010-12-10|2012-06-14|Basawaraj Chickmath|Testosterone undecanoate compositions|

EA028217B1|2010-12-27|2017-10-31|Такеда Фармасьютикал Компани Лимитед|Orally disintegrating tablet |

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WO2013088109A1|2011-12-16|2013-06-20|Oxagen Limited|Combination of crth2 antagonist and a proton pump inhibitor for the treatment of eosinophilic esophagitis|

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CN104203938A|2012-01-21|2014-12-10|朱比兰特生命科学有限公司|Process for the preparation of 2-pyridinylmethylsulfinyl benzimidazoles, their analogs and optically active enantiomers|

EA201591338A1|2013-01-15|2016-01-29|Айронвуд Фармасьютикалз, Инк.|GASTRORETENTIVE MEDICAL FORM OF SECRESTRANATE OF BILIC ACIDS, SLOWLY RELEASED FOR ORAL APPLICATION|

US10004691B2|2013-05-21|2018-06-26|Takeda Pharmaceuticals Company Limited|Orally disintegrable tablet|

WO2016033556A1|2014-08-28|2016-03-03|Lipocine Inc.|BIOAVAILABLE SOLID STATE -HYDROXY-4-ANDROSTEN-3-ONE ESTERS|

US20180015118A1|2015-02-03|2018-01-18|Ironwood Pharmaceuticals, Inc.|Methods of treating upper gastrointestinal disorders in ppi refractory gerd|

WO2016174664A1|2015-04-29|2016-11-03|Dexcel Pharma Technologies Ltd.|Orally disintegrating compositions|

US10736855B2|2016-02-25|2020-08-11|Dexcel Pharma Technologies Ltd.|Compositions comprising proton pump inhibitors|

US10076494B2|2016-06-16|2018-09-18|Dexcel Pharma Technologies Ltd.|Stable orally disintegrating pharmaceutical compositions|

CN107365300B|2017-07-26|2019-08-02|桂林华信制药有限公司|A method of effectively removing impurity in Lansoprazole crude product|

法律状态:
2005-08-10| REG| Reference to a code of a succession state|Ref country code: RU Ref legal event code: PD4A |

优先权:

申请号 | 申请日 | 专利标题

JP59171069A|JPH0244473B2|1984-08-16|1984-08-16|LV920583A| LV5091A3|1984-08-16|1992-12-30|Method of obtaining pyridine derivatives|

LTRP440A| LT2118B|1984-08-16|1993-03-19|PIRIDINE'S WAY OF RECEIVING|

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