CA1127158A - 2-pyridylmethylsulfinyl-benzimidazole compounds - Google Patents

2-pyridylmethylsulfinyl-benzimidazole compounds

Info

Publication number
CA1127158A
CA1127158A CA325,188A CA325188A CA1127158A CA 1127158 A CA1127158 A CA 1127158A CA 325188 A CA325188 A CA 325188A CA 1127158 A CA1127158 A CA 1127158A
Authority
CA
Canada
Prior art keywords
methyl
hydrogen
benzimidazole
methoxy
dimethyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired
Application number
CA325,188A
Other languages
French (fr)
Inventor
Ulf K. Junggren
Sven E. Sjostrand
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Hassle AB
Original Assignee
Hassle AB
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=20334608&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CA1127158(A) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Hassle AB filed Critical Hassle AB
Priority to CA386,943A priority Critical patent/CA1129417A/en
Application granted granted Critical
Publication of CA1127158A publication Critical patent/CA1127158A/en
Expired legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents

Abstract

Abstract The present invention relates to novel compounds of the formula

Description

~` 1127158 AB H~SSLE
Molndal/SWEDEN

`~ Inventors: U Junggren and S E Sjostrand UI/LB/EMH

Gastric acid sscretion agents . ~ .
The present invention relates to new compounds having valuable properties in affecting gastric acid secretion in ~ mammals, including man, as well as the process for their ~ preparation, method of affecting gastric acid secretion and pharmaceutical preparations containing said no~el compounds.

The object of the present invention is to obtain compound5 which affect gastric acid secretion, and which inhibit exogenously or endogenously stimulated gastric acid secre-tion. These compounds can be used in the treatment of peptic ~ ~ ulcer disease.
`,:
i It is previously known that compounds of the formulas I and II

~, ;

, . .
~ .

llZ715~
~2 Rl ~ ~ S R4 ~ (I~

Rl ~ \ ~ S-R4 ~ ( I I ) wherein Rl and R2 are each selected from the group consist-ing of hydrogen, alkyl, halogen, cyano, carboxy, carboxy- :
` 15 alkyl, carboalkoxy, carboalkoxyalkyl, carbamoyl, carbamoyl-oxy, hydroxy, alkoxy, hydroxyalkyl, trifluoromethyl and acyl in any position, R3 is selected from the group con-: sisting of hydrogen, alkyl, acyl, carboalkoxy, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, alkylcarbonylmethyl, alkoxycarbonylmethyl, and alkylsulphonyl, and R4 is selected ~ from the group consisting of straight and branched alkylene ;~ groups having 1 to 4 carbon atoms, whereby at most one methylene group is present between S and the pyridyl ~roup, and whereby the pyridyl group may be further substituted ZS with alkyl or halogen, possess inhibiting effect of gastric :: acid secretion.

It has now, however, surprisingly been found that the compounds defined belaw possess a still ~reater inhibiting effect than those given abave.

: Campaunds af the inventian are those af the general formula ~ 35 ~ ~ R5 ~ (III~

'! H

'~ ' ' ' ~'' ~, L ~

llZ715~3 in which Rl and R2 are the same or different and are selected from the group consisting of hydrogen, alkyl, halogen, carbomethoxy, carbethoxy, alkoxy and alkanoyl in any position, R is selected from the group consisting of hydro-gen, methyl, and ethyl, R3, R4 and R5 are the same or different and are each selected from the group consisting of hydrogen, methyl, methoxy, ethoxy, methoxyethoxy, and ethoxyethoxy, with the proviso that R3, R4 and R5 are not all hydrogen, and the further proviso that when two of R , R and R are hydrogen, the third of R3, R4 and R5 is not methyl.
The invention also extends to therapeutically acceptable salts of compounds of formula III.
Alkyl R and R of formula III are suitably alkyl having up to 7 carbon atoms, preferably up to 4 carbon atoms. Thus, alkyl R may be methyl, ethyl, n-propyl, isopropyl, n-butyl or isobutyl.
Halogen R and R is chloro, bromo, fluoro or iodo.
Alkoxy R and R are suitably alkoxy groups having up to 5 carbon atoms, preferably up to 3 carbon atoms, as methoxy, ethoxy, n-propoxy or isopropoxy.
Alkanoyl Rl and R2 have preferably up to 4 carbon atoms and are e.g. formyl, acetyl or propionyl, preferably acetyl.
A preferred group of compounds of the general formula III are those wherein Rl and R2 are the same or different and are each selected from the group consisting of hydrogen, alkyl, carbomethoxy, alkoxy, and alkanoyl, whereby R and R2 are not both hydrogen, R is hydrogen, and R3, R4 and R
are the same or different and are each selected from the group consisting of hydrogen, methyl, methoxy and ethoxy, whereby R3, R4 and R are not all hydrogen, and whereby when two of R3, R4 and R5 are hydrogen the third of R3, R4 and R5 is not methyl.

~lZ715~

..
A second preferred group of compounds of the general formula III are those wherein Rl and R2 are the same or different and are each selected from the group consisting of hydrogen, alkyl, halogen, caroomethoxy, carbethoxy, alkoxy, and alkanoyl, 5 R6 is select'ed from the group consisting of hydrogen, methyl, and ethyl, R3 is methyl, R4 is methoxy, and R5 is methyl.

A third preferred group of compounds of the general formula III are those wherein Rl and R2 are the same or different 10 and are each selscted from the group consisting of hydrogen, alkyl, halogen, carbomethoxy, caroethoxy, alkoxy and alkanoyl, R is selected from the group consisting of hydrogen, methyl and ethyl~ and R3 is hydrDgen, R4 is methoxy and R5 is methyl or R3 is methyl, R4 is methoxy and R5 is hydrogen.
A fourth preferred group of compounds of the general formula III are those wherein Rl and R2 are the same or different and are each selected from the group consisting of hydrogen, alkyl, halogen, carbomethoxy, carbethoxy, alkoxy, and alkanoyl, 20 R6 is selected from the group consisting of hydrogen, methyl and ethyl, R3 and R are hydrogen and R4 is methoxy.
.
A fifth preferred group of compounds of the general formula III are those wherein Rl and R2 are the same or different J . -:
.' 25 and are each selected from the group consisting of hydrogsn, alkyl, halogen, carbomethoxy, carbethoxy, alkoxy, and alkanoyl, R6 is selected from the group consisting of hydrogen. methyl and ethyl, and R3 and R5 are methyl and R4 i9 hydrogen.
... .
30 A sixth preferred group of compounds of the general formula III are those wherein Rl and R2 are the same or different and are each selected from the group consisting of hydrogen, alkyl, halogenJ carbomethoxy, carbethoxy, alkoxy, and alkanoyl~
'~i R is selected from the group consisting of hydrogen, methyl 35 and ethyl, R and R are hydrogen and R4 is ethoxy. methoxy-ethoxy or ethoxyethoxy.

~ .

11~7158 A seventh prefPrred group of compounds o-F the general formula III are thnse wherein Rl and R2 are the same or different and are each selected from the group consisting of hydrogen, alkyl, halogen, carbomethoxy, alkoxy, and alkanoyl, R6 is selected from the group consisting of hydrogen, methyl, and ethyl, R3, R4, and R5 are all methyl.

Compounds of formula III above may be prepared according to the following methods:
a) oxidizing a compound of formula IV

Rl ~ N ~ RS R5 (IV~

wherein R , R2, R6, R3. R4, and R5 have the meanings given, to the formation of a compound of formula III.
b) reacting a compound of the formula V '.

.5 Rl ~ ~ S-l -M (V) 1~1 .~ .

wherein Rl, R2, and R6 have the meanings given above and M is a metal selected from the group consisting of K, Na and Li, with a compound of formula VI.

~ (~

11~715~

wherein R3, R4, and R5 have the same meanings as given above, Z is a reactive esterified hydroxy group, to the formatinn of a compound of formula III;

c) reacting a compound of the formula VII
~2 R~ VII) wherein Rl, and R2 have the same meanings as given above and zl is SH or a reactive esterified hydroxy group, with a compound of the formula VIII

R3 ~ R5 ~VIII) Z2-lH ~ J

; wherein R6, R3, R4, and R5 have the same meanings as given above, and z2 is a reactive esterified hydroxy group or SH, to the formation of an intermediate of formula IV above, which then i5 oxidized to give a compound of formulà III;

d) reacting a compound of the formula IX
- R~
., 1 ~NH2 R ~ NH2 (IX~

wherein Rl and R2 have the same meanings as given above with a compound of the formula X
`~ 35 11~715~

R3`~ R5 (X) HOOC-S-~H - ~

wherein R6, R3, R4, and R5 have the same meanings as given above, to the formation of an intermediate of formula IV
above, which then is oxidized to give a compound of formula III, which compound may be converted to its therapeutical~y ; acceptable salts, if so desired.

In the reactions above, z, zl, and z2 may be a reactive, esterified hydroxy group which i5 a hydroxy group esterified with strong, inorganic or organic acid, preferably a hydro-halogen acid, such as hydrochloric acid, hydrobromic acid, or hydroiodic acid, also sulfuric acid or a strong organic sulfonic acid as a strong aromatic acid, e.g. benzene-~ sulfonic acid, 4-bromobenzenesulfonic acid or 4-toluene-; 20 sulfonic acid.

The oxidation of the sulfur atom in the chains above to sulfinyl (S-~0) takes place in the presence of an oxidizing I agent selected from the group consisting of nitric acid, ,f ` 25 hydrogen peroxide, peracids, peresters, ozone, dinitrogen-tetraoxideJ iodosobenzene, N-halosuccinimide, l-chlorobenzo-triazole, t-butylhypochlorite, diazobicyclo-r2,2,2]-octane bromine complex, sodium metaperiodate, selenium dioxide, . manganese dioxide, chromic acid, cericammonium nitrate, bromineJ chlorine, and sulfuryl chloride. The oxidation usually takes place in a solvent wherein the oxidizing agent i5 present in some excess in relation to the product to be oxidized. -~:
j 35 Oepending on the process conditions and the starting mater`
ials, the end product is obtained either as the free base or in the acid addition salt, both of which are included within the scope of the invention. Thus, basicJ neutral or or mixed salts may be obtained as well as hemiJ monoJ sesqui llZ7~S~

or polyhydrates. The acid addition salts of the new compounds may in a manner known per se be transformed into free base using basic agents such as alkali or by ion exchange. On the other hand, the free bases obtained may form salts with organic or inorganic aoids. In the prepara-tion of acid addition salts preferably such acids are used which form suitable therapeutically acceptable salts. Such acids include hydrohalogen acids, sulfonic, phosphoric, nitric, and perchloric acids; aliphatic, alicyclic, aromatic, heterocyclic carboxy or sulfonic acids, such as formic, acetic, propionic, succinic, glycolic, lactic, malic, tartaric, citric, ascorbic, maleic, hydroxymaleic, pyruvic, phenylacetic, benzoic, p-aminobenzoic, antranilic, ` ~p-hydroxybenzoic, salicylic or p-aminosalicylic acid, embonic, methanesulfonic, ethanesulfonic, hydroxyethane-sulfonic, ethylenesulfonic, halogenbenzenesulfonic, toluene-sulfonic, naphtylsulfonic or sulfanilic acids; methionine, tryptophane, lysine or arginine.

, ,20 These or other salts of the new compounds, as e.g. picrates, may serve as purifying agents of the free bases obtained.
Salts of the bases may be formed, separated from solution, and then the free base can be recovered from a new salt solution in a purer state. Because of the relationship between the new compounds in free base form and their salts, it will be understood that the corresponding salts are ':
included within the scope of the invention.

'Some of the new compounds may, depending on the choice of ;`30 starting materials and process, be pressnt as optical isamers or racemate, or if they contain at least two asymmetric carbon atoms, be present as an isomer mixture tracemate -~ mixture).
" ~
Ths isomer mixtures (racemate mixtures) obtained may be separated into two stereoisomeric ~diastereomeric) pure racemates by means of chromatography or -Fractional crystal-.

.

15~3 g lization.

The racemates obtained can be separated according to knownmethods, e.g. recrystallization from an optically active solvent, use of microorganisms, reactions with optically active acids forming salts which can be separated, separa-; tion based on different solubilities of the diastereomers.
Suitable optically active acids are the L- and D-forms of tartaric acid, di-o-tolyl-tartaric acid, malic acid, mandelic acid, camphorsulfonic acid or quinic acid, Prefer-ably the more active part of the two antipodes is isolated.

The starting materials are known or may, if they should be new, be obtained according to processes known per se.
In clinical use the compounds of the invention are administ-ered orally, rectally or by injection in the form of -a pharmaceutical preparation which contains an active component either as a free base or as a pharmaceutically acceptable, , 20 non-toxic acid addition salt, such as hydrochloride, lactate, acetate, sulfamate, in combination with a pharmaceutically acceptable carrier. The carrier may be in the-form of a solid, semisolid or liquid diluent, or a capsule. These pharmaceutical preparations are a further object of the 25 ~invention. Usually the amount of active compound is between 0.1 to 95 % by wèight of the prsparation, between 0.5 to 20 % by weight in preparations for injection and between 2 and 50 ~O by weight in preparations for oral administration.

i 30 In the preparation of pharmaceutical preparations containing a compound of the present invention in the form of dosage ~` units for oral administration the compound selected may be ~, ~ mixed with a solid, pulverulent carrier, such as lactose, saccharose, sorbitol, mannitol, starch, amylopectin, i 35 cellulose derivatives or gelatin, as well as with an anti-friction agent such as magnesium stearate, calcium stearate.
and polyethyleneglycol waxes. The mixture is then pressed ~1~715~3 into tablets. If coated tablets are desired, the above prepared core may be coated with a concentrated solution of sugar, which may contain gum arabic, gelatin, talc, titanium dioxide or with a lacquer dissolved in volatile organic solvent or mixture of solvents. To this coating various dyes may be added in order to distinguish among ; tablets with different active compounds or with different amounts of the active compound present.

Soft gelatin capsulss may be prepared which capsules contain a mixture oF the active compound or compounds of the invention and vegetable oil. Hard gelatin capsules may contain granules of the active compound in co~bination with a solid, pulverulent carrier as lactose, saccharose, sorbi-tol, mannitol, potato starch, corn starch, amylopectin,cellulose derivatives or gelatin.

Dosage units for rectal administration may be prepared in the form of suppositories which contain the active substance in a mixture with a neutral fat base, or they may be prepared in the form of gelatin-rectal capsules which contain the active substance in a mixture with a vegetable oil or paraffin - oil.

Liquid preparations for oral administration may be prepared in the form of syrups or suspensions, e.g. solutions contain-ing from O.Z % to 20 % by weight of the active ingredient and the remaindar consisting of sugar and a mixture of ethanol, water, glycerol and propylene glycol. If desired, such liquid preparations may conta`in colouring agents, flavouring agents, saccharin and carboxymethylcellulose as a thickening agent.

Solutions for parenteral administration by injection may be prepared as an aqueous solution of a watersoluble pharma-ceutically acceptable salt of the active compound, prefer-ably in a concentration from 0.5 % to 10 % by weight. These solutions may also contain stabilizing agents and/or 11~7~58 buffering agents and may be manufactured in different dosage unit ampoules.

Pharmaceutical tablets for oral use are prepared in the following manner: The solid substances are ground or sieved to a certain particle size, and the binding agent is homo-genized and suspended in a suitable solvent. The therapeut-ically active compounds and auxiliary agents are mixed with the binding agent solution. The resulting mixture is moistened to form a uniform suspension having the consist-ency of wet snow. The moistening causes the particles to aggregate slightly, and the resulting mass is pressed through a stainless steel sieve having a mesh size of approximately 1 mm. The layers of the mixture are dried in carefully controlled drying cabinets for approximately ten hours to obtain the desired particle size and consistency. The granules of the dried mixture are sieved to remove any powder. To this mixture, disintegrating, antifriction and antiadhesive agents are added. Finally, the mixture is pressed into tablets using a machine with the appropriate punches and dies to obtain the desired tablet size. The pressure applied affects the size of the tablet, its strength and its ability to dissolve in water. The compression ; pressure used should be in the range O.S to 5 tons. Tablets are manufactured at the rate of 20.000 to 200.000 per hour.
The tablsts, especially those which are rough or bitter, may be coated with a layer of sugar or some other palatable substance. Thay are then packaged by machines having elect-ronic counting devices. The different types of packages ; 30 consist of glass or plastic gallipots, boxes, tubes and specific dosage adapted packages.

The typical daily dose of the active substance varies according to the individual needs and the manner of adminis-tration. In general, oral dosages range from 100 to 400mg/day of active substance and intravenous dosages range -from 5 to 20 mg/day.

.

11;~7158 The following illustrates a preferred embodiment of the invention without being limited thereto. Temperature is given in degrees Centigrade.
:
The starting materials in the examples found below were prepared in accordance with the following methods:
- ~1) a 1,2-diamino compound~ such as o-phenylenediamine was reacted with potassium ethylxanthate ~according to Org.
Synth. Vol. 30, p. 56) to form a 2-mercaptobsnzimidazole;
~2) the compound 2-chloromethylpyridine was prepared by reacting 2-hydroxymethylpyridine with thionylchloride ~according to Arch. Pharm. Vol. 26, pp. 448-451 ~1956));
(3) the compound 2-chloromethylbenzimidazole was prepared by condensing o-phenylenediamine with chloroacetic acid.
Example 1 ~, .
28.9 g of 2-[2-~4,5-dimethyl)pyridylmethylthio]-(5-acetyl--6-methyl)-benzimidazole were dissolved in 160 ml of CHC13, . 20 24.4 g of m-chloroperbenzoic acid were added in portions while stirring and cooling to 5C. After 10 minutes, the precipitatsd m-chlorobenzoic acid was filtered off. The filtrate was diluted with CH2C12, washed with Na2C03 solu-tion~ dried over Na2S04 and evaporated in vacuo. The residue crystallized when diluted with CH3CN, and 2-[2-~4,5-di-methyl)pyridylmethylsulfinyl~-(5-acetyl-6-methyl)benzimid-azole was recrystallized from CH3CN. Yield 22.3 g; m.p.
158C.
;' ~ ' ' - 30 Examples 2-30 The preparation of compounds of formula III labelled 2-26 was carried out in accordance with Example 1 above. The compounds prepared are listed in Table 1 which identifies the substituents for these compounds.

I

11~7158 Example 31 ~method c) 0.1 moles of 4-6-dimethyl-2-mercaptobenzimidazole were dissolved in 20 ml of water and Z00 ml of ethanol contain-ing 0.2 moles of sodium hydroxide. 0.1 moles of Z-chloro-methyl-(3,5-dimethyl)pyridine hydrochloride were added and the mixture was refluxed for two hours. The sodium chloride formed was filtered off and the solution was evaporated in vacuo. The residue was dissolved in acetone and was treated with active carbon. An equivalent amount of concentrated hydrochloric acid was added, whereupon the mono-hydro-; chloride of 2-[2-(3,5-dimethyl)pyridylmethylthio]-(4,6-di-methyl)benzimidazole was isolated. Yield 0.05 moles.

This compound was then oxidized in accordance with Example 1 above to give the corresponding sulfinyl compound, melting point 50-55C.

Example 32 (method b) 0.1 moles of 2-rLi-methylsulfinyl](5-acetyl-6-methyl)-benzimidazole were dissolved in 150 mls of benzene. 0.1 moles
2-chloro-(3,5-dimethyl)pyridine were added and the mixture was refluxed for two hours. The lithiumchloride formed was filtered off, and the solution was evaporated in vacuo.
The residue was crystallized from CH3CN, and recrystallized from the same solvent. Yield 0.82 moles of 2-[2-(3,5-di-methyl)pyridylmethylsulfinyl~-(5-acetyl-6-methyl)benzimid-a~ol-e melting at 171C.
Example 33 (method d) 23.4 g of 2-[2-(3,4,5-trimethyl)pyridylmethylthio] formic acid - and 16.6 g of o-(5-acetyl-6-methyl)phenylenediamine were boiled for 40 minutes in 100 ml of 4N HCl. The mixture was cooled and neutralized with ammonia. The neutral solution was then extracted with ethyl acetate. The organic phase was !

11'~,715~3 . .
`treated with active carbon and evapQrated ln _acuo. The residue was dissolved in acetone whereupon an equivalent of concentrated HCl was added. The precipitated hydro-chloride was filtered off after cooling and the salt was - 5 recrystallized from absolute ethanol and some ether. Yield of 2-[2-(3,4,5-trimethylpyridyl)methylthio]-(5-acetyl-6-methyl)benzimidazole was 6.5 g.

This compound was then oxidizèd in accordance with Example 1 above, to give the corresponding sulfinyl derivative.
M.p. 190C.

Example 34 (method c) .'. ~ ~ .
22.0 g of 2-mercapto-(5-acetyl-6-methyl)benzimidazole and 19.5 g of chloromethyl(4,5-dimethyl)pyridine hydrochloride were dissolved in 200 ml of 95 % ethanol. 8 g of sodium hydroxide in 2~ ml of water were added, whereupon the solu-tion was refluxed for two hours. The sodium chloride formed , 20 was filtered off and the solution was evaporated in vacuo.
The residue, 2-[2-(4,5-dimethyl)pyridylmethylthio]-(5-acetyl-6-methyl)benzimidazole, was recrystallized from 70 ~ ethanol.
Yield 10.6 g.
' This compound was then oxidized in accordance with Example 1 above, to give the corresponding sulfinyl derivative.
M.p. 158C;

` '', ~ ~ .

~ ~ ~ RB

Ex. Rl R2 R6 R3 R4 R5 M.p.
C
.. .
3 5-COOCH3 H H H CH3 CH3 141 : ~ 15 5 COCH3 6 CH3 H C.H3. CH3. H 160 :. 5 5-COOCH3 6-CH3 H CH3 ~ CH3. H 163 : 6 4-CH3 6-CH3 H CH3 H CH3 50-55 7 5-COCH3 6-CH3 H CH3 H ` CH3 171 8 5-COCH3 6 CH3 H CH3 EH3 ~ CH3 190 , 20 9 5-COCH3 6-CH3 H H OCH3 H 165
4-CH3 6-CH3 H H OCH3 H 122 .
., 11 5 COCH3 6 CH3 H CH3 OCH3 CH3 156 .` . 12 5-COOCH3 6-CH3 H CH3 H CH3 144 13 H3 6 GH3 H CH3 CH3 CH3 lB5 . 25 14 5-COOCH3 6-CH3 H H OCH3 H 1.69
5-COOCH3 6-CH3 H H OC2H5 H 148 . 17 5-COOCH3 6-CH3 H CH3 OCH3 CH3 155 .. 30 19 5-COOCH3 H H CH3 H CH3 141 5-COOCH3 H H CH3 OCH~ CH3 142 . 21 5-COCH3 H H CH3 0CH3 ` CH3 162 . ~ 22 5-OCH3 H H H OCH3 CH3 178 . . 23 5-OCH3 H H CH3 OCH3 CH3 156 '. 35 24 5-CH3 H H CH3 OCH3 CH3 181 . , 26 5-Cl H H CH~ OCH3 CH3 185 5-CH3 3 3.. _ CH3 152 .

~1~7~5~

.
Biological e~fect The compounds of the invention possess worthwhile thera-peutic properties as gastric acid secretion inhibitors as demonstrated by the following tests. To determine the gastric acid secretion inhibitory properties, experiments have been performed on conscious dogs provided with gastric fistulas of conventional type and duodenal fistulas, the latter ones used for direct intraduodenal administration of the test compounds. After 18 hours starvation and depriv-; ation of water the dogs were givsn a subcutaneous infusion of pentagastrin (1-4 nmol/kg, h) lasting for 6-7 hours.
Gastric juice was collected in consecutive 30 minutes ; samples. An aliquot of each sample was titrated with 0.1 N
NaOH to pH 7.0 for titrable acid concentration using an automatic titrator and pH-meter (Radiometer, Copenhagen, Denmark). Acid output was calculated as mmol H /60 minutes.
The percent inhibition compared to control experiments was calculated for each compound and the peak inhibitory effect is given in Table 2 below. The test compounds,--suspended in 0.5 % Methocel~ (methyl cellulose), were given intraduoden-ally in doses from 4-20 ~mol/kg when the secrstory response to pentagastrin has reached a steady level.
~`:
. : :
In the test prior known compounds were compared with the compounds of the present invention as will be evident from ~-~ the Table 2 below.
, ~ .
.~ ~ . , .

, The following gastric acid inhibiting effect data were obtained for a number of compounds tested according to the . method dsscribed.

- i ~

. I .

~i27158 Table 2 R

H

~`
Ex. Rl R2 R6 R3 R4 R5 Dose Effect -~mol/k~ % inhibition _ .

a 5 COCH3 6 CH3 H CH3 CH3 CH3 4 100 5 COCH3 6-CH3 H CH3 OCH3 CH3 0.5 70 x 5-COCH3 6-CH3 H H CH3 H 20 30 x 5-COCH3 6-CH3 H H H CH3 8 80 ., 20 2 5-COOCH3 6-CH3 H H CH3 3 60 ;' 5 5-COOCH 6-CH H CH3 CH H 2 90 . ' 12 5-COOCH3 6-CH3 H CH3 H CH3 2 70 .
: 13 5 C CH3 6 CH3 H CH3 C 3 3 4 RO

: 25 15~ 5-COOCH3 6-CH3 H H OC~H5 H 4 75 : 16 5-COOCH3 6-CH3 H CH3 OCH3 H 0.5 65 : 17 5-COOCH3 6-CH3 H CH3 OCH3 CH3 0.5 90 18 s-cOOCH3 6-CH3 H H OCH3 CH3 30 x 5-COOCH3 6-CH3 H Or H H 4 a ~: ' .

, oont.

:~ ;

.

11~71S8 ] ~
Ex Rl R2 R6 R3 R4 R5 Dose Effect ~mol/kg % inhibition 5 ~20 5-COOCH3 H H CH3 OCH3 CH3 0 5 65 x 5-COOCH3 H H H H CH3 20 90 x 5-COOCH3 H H H H H 20 50 10 x 5-COCH3 H H H H C2H5 20 40 23 5-OCH3 H H CH3 OCH3 CH3 0~5 65 . x 5-OCH3 ' H ~ H CH3 ~ 20 10 : 15 24 5-CH H H CH3 OCH3 CH3 0.5 50 x 5-CH3 H H H H CH3 4 50 ; . x H H H H H H 4 50 . 20 2B. 5-COOC2H5 H H CH3 OCH3 CH~ 0.5 50 26 5-Cl H H CH3 OCH3 CH3 0-5 25 27 5-CH H H H OC2H4ocH3 H 0.5 30 . .

: x denotes a previously known compound ~

.:, ... .. . .. ~ .
Example 35 A syrup containing 2 % (weight per volume~ of acti~e substance was prepared from the following ingredients:

2-[2-(4,5-dimethyl)pyridylmethylsulfinyl]--(5-acetyl-6-methyl)benzimidazole HCl 2.0 g Saccharin 0.6 g Sugar 30.0 g 35 Glycerin - 5.0 g Flavouring agent 0.1 g Ethanol 96 % 10.0 ml Distilled water (sufficient to obtain a final volume of 100 ml~

~lZ7~58 Sugar, saccharin and the acid addition salt were dissolved in 60 g of warm water. After cooling, glycerin and a solu-tion of flavouring agents dissolved in ethanol were added.
To the mixture water was added to obtain a final volume of 100 ml.

The above given active substance may be replaced with other pharmaceutically acceptable acid addition salts.

Example 36 2-[2-~3,4-dimethyl)pyridylmethylsulfinyl]-~5-acetyl-6--methyl)benzimidazole HCl (250 g~ was mixed with lactose (175.8 g), potato starch (169.7 g) and colloidal silicic acid (32 g). The mixture was moistened with 10 % solution of gelatin and was ground through a 12-mesh sieve. After drying, potato starch (160 g), talc (50 g) and magnesium ; ~ stearate (5 g) were added and the mixture thus obtained was pressed into tablets (10.000), with each tablet containing , 20 25 mg of active substance. Tablets can be prepared that i contain any desirsd amount of the active ingredient.
;
Example 37~

Granules were prepared from 2-[2-(3,5-dimethyl)pyridyl-methylsulfinyl]-(5-acetyl-6-methyl)benzimidazole-p-hydroxy-benzoate (250 g), lactose (175.9 g) and an alcoholic solu-` tion of polyvinylpyrrolidone (25 g). After drying, the granules were mixed with talc t25 g), potato staroh t40 g), and magnesium stearate ~2.50 g) and were pressed into 10.000tablets. These tablets are first coated with a 10 % alcoholic solution of shellac and thereupon with an aqueous solution ~ ~ containing saccharose (45 %), gum arabic (5 ~), gelatin (4%), -~ and dyestuff (0.2 %). Talc and powdered sugar were used for powdering after the first five coatings. The coating was then ; covered with a 66 % sugar syrup and polishsd with a solution of 10 % carnauba wax in carbon tetrachloride.

11~7158 Example 3~

2-[2-(3,5-dimethyl)pyridylmethylsulfinyl~-(5-acetyl-6--methyl)benzimidazole hydrochloride (1 g)J sodium chloride (0.6 g) and ascorbic acid (0.1 g~ were dissolved in sufficient amount of distilled water to give 100 ml of solution. This solution, which contains 10 mg of active substance for each ml, was used in filling ampoules, which were sterilized by heating at 120C for 20 minutes.

, .
, -!
' '`'~

.

' !
,~, : , ~ J~
..,~ 1, ~':~: i ' .

Claims (89)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A process for preparing a compound of the general formula III

III

or a therapeutically acceptable salt thereof in which R1 and R2 are the same or different and are selected from the group consisting of hydrogen, alkyl, halogen, carbomethoxy, carbethoxy, alkoxy and alkanoyl in any position, R6 is selected from the group consisting of hydrogen, methyl, and ethyl, R3, R4 and R5 are the same or different and are each selected from the group consist-ing of hydrogen, methyl, methoxy, ethoxy, methoxyethoxy, and ethoxyethoxy, with the proviso that R3, R4 and R5 are not all hydrogen, and the further proviso that when two of R3, R4 and R5 are hydrogen, the third of R3, R4 and R5 is not methyl, which process comprises:
(a) oxidizing a compound of formula IV

IV

wherein R1, R2, R6, R3, R4 and R5 are as defined above to form a compound of formula III; or (b) reacting a compound of the formula V

V

wherein R1, R2 and R6 are as defined above, and M is a metal selected from the group consisting of K, Na, and Li with a compound of formula VI

VI

wherein R3, R4 and R5 are as defined above, and Z is a reactive esterified hydroxy group, to form a compound of formula III; or (c) reacting a compound of formula VII

VII

wherein R1 and R2 are as defined above and Z1 is SH, or a reactive esterified hydroxy group, respectively, with a compound of formula VIII

VIII

wherein R6, R3, R4 and R5 are as defined above and Z2 is a reactive esteri-fied hydroxy group or SH, respectively to farm an intermediate of formula IV, which then is oxidized to give a compound of formula III; or (d) reacting a compound of formula IX

IX

wherein R1 and R2 are as defined above with a compound of the formula X

X

wherein R6, R3, R4 and R5 are as defined above, to form an intermediate of formula IV, which then is oxidized to give a compound of formula III, and, if required, converting a salt to the free base or converting a free base to a therapeutically acceptable salt.
2. A process according to claim 1(a) wherein the compound of formula IV is obtained by reacting a compound of formula VII

VII

wherein R1 and R2 are as defined in claim 1 and Z1 is SH, or a reactive esterified hydroxy group, respectively, with a compound of formula VIII

VIII

wherein R6, R3, R4 and R5 are as defined in claim 1 and Z is a reactive esterified hydroxy group or SH, respectively.
3. A process according to claim 1(b) wherein the compound of formula IV is obtained by reacting a compound of formula IX

IX

wherein R1 and R2 are as defined in claim 1 with a compound of the formula X

X

wherein R6, R3, R4 and R5 are as defined in claim 1.
4. A process according to claim 1, 2 or 3 in which R1 is hydrogen, chloro, methyl, ethyl, methoxy, acetyl, carbethoxy or carbomethoxy, R2 is hydrogen, or methyl, R6 is hydrogen, methyl or ethyl, R3 and R5 are methyl, and R4 is methoxy.
5. A process according to claim 1, 2 or 3 in which R1 is hydrogen, chloro, methyl, ethyl, acetyl, methoxy, carbethoxy or carbomethoxy, and R2 is hydrogen, methyl or ethyl, R6 is hydrogen, methyl or ethyl, R4 is methoxy and R3 is hydrogen and R4 is methyl, or R3 is methyl and R5 is hydrogen.
6. A process according to claim 1, 2 or 3 wherein R1 is methyl in the 4-position, acetyl in the 5-position, carbomethoxy in the 5-position or carbethoxy in the 5-position, R2 is methyl in the 6-position, R6 is hydrogen, R3 is hydrogen or methyl, R4 is hydrogen, methyl, methoxy or ethoxy and R5 is hydrogen or methyl.
7. A process according to claim 1, 2 or 3 wherein R1 is hydrogen, methyl in the 5-position, chlorine in the 5-position, methoxy in the 5-position, carbomethoxy in the 5-position, carbethoxy in the 5-position, R2 is hydrogen, R6 is hydrogen or methyl, R3 is hydrogen or methyl, R4 is hydrogen, methyl, methoxy or methoxyethoxy and R5 is hydrogen or methyl.
8. A compound of formula III as defined in claim 1 or a therapeuti-cally acceptable salt thereof when prepared by a process according to claim 1 or an obvious chemical equivalent thereof.
9. A process according to claim 1, 2 or 3 wherein R1 is 5-COCH3, R2 is 6-CH3, R6 is hydrogen, R3 is methyl, R4 is methyl and R5 is hydrogen.
10. A process according to claim 1, 2 or 3 wherein R1 is 4-CH3, R2 is 6-CH3, R6 is hydrogen, R3 is methyl, R4 is hydrogen and R5 is methyl.
11. A process according to claim 1, 2 or 3 wherein R1 is 5-COOCH3, R2 is hydrogen, R6 is hydrogen, R3 is hydrogen, R4 is methyl and R5 is methyl.
12. A process according to claim 1, 2 or 3 wherein R1 is 5-COCH3, R2 is 6-CH3, R6 is hydrogen, R3 is hydrogen, R4 is methyl and R5 is methyl.
13. A process according to claim 1, 2 or 3 wherein R1 is 5-COOCH3, R2 is 6-CH3, R6 is hydrogen, R3 is hydrogen, R4 is methyl and R5 is methyl.
14. A process according to claim 1, 2 or 3 wherein R1 is 5-COOCH3, R2 is 6-CH3, R6 is hydrogen, R3 is methyl, R4 is methyl and R5 is hydrogen.
15. A process according to claim 1, 2 or 3 wherein R1 is 5-COCH3, R2 is 6-CH3, R6 is hydrogen, R3 is methyl, R4 is hydrogen and R5 is methyl.
16. A process according to claim 1, 2 or 3 wherein R1 is 5-COCH3, R2 is 6-CH3, R6 is hydrogen, R3 is methyl, R4 is methyl and R5 is methyl.
17. A process according to claim 1, 2 or 3 wherein R1 is 5-COCH3, R2 is 6-CH3, R6 is hydrogen, R3 is hydrogen, R4 is OCH3 and R5 is hydrogen.
18. A process according to claim 1, 2 or 3 wherein R1 is 4-CH3, R2 is 6-CH3, R6 is hydrogen, R3 is hydrogen, R4 is OCH3 and R5 is hydrogen.
19. A process according to claim 1, 2 or 3 wherein R1 is 5-COCH3, R2 is 6-CH3, R6 is hydrogen, R3 is methyl, R4 is OCH3 and R5 is methyl.
20. A process according to claim 1, 2 or 3 wherein R1 is 5-COOCH3, R2 is 6-CH3, R6 is hydrogen, R3 is methyl, R4 is hydrogen and R5 is methyl.
21. A process according to claim 1, 2 or 3 wherein R1 is 5-COOCH3, R2 is 6-CH3, R6 is hydrogen, R3 is methyl, R4 is methyl and R5 is methyl.
22. A process according to claim 1, 2 or 3 wherein R1 is 5-COOCH3, R2 is 6-CH3, R6 is hydrogen, R3 is hydrogen, R4 is OCH3 and R5 is hydrogen.
23. A process according to claim 1, 2 or 3 wherein R1 is 5-COOCH3, R2 is 6-CH3, R6 is hydrogen, R3 is hydrogen, R4 is OC2H5 and R5 is hydrogen.
24. A process according to claim 1, 2 or 3 wherein R1 is 5-COOCH3, R2 is 6-CH3, R6 is hydrogen, R3 is methyl, R4 is OCH3 and R5 is hydrogen.
25. A process according to claim 1, 2 or 3 wherein R1 is 5-COOCH3, R2 is 6-CH3, R6 is hydrogen, R3 is methyl, R4 is OCH3 and R5 is methyl.
26. A process according to claim 1, 2 or 3 wherein R1 is 5-COOCH3, R2 is 6-CH3, R6 is hydrogen, R3 is hydrogen, R4 is OCH3 and R5 is methyl.
27. A process according to claim 1, 2 or 3 wherein R1 is 5-COOCH3, R2 is hydrogen, R6 is hydrogen, R3 is methyl, R4 is hydrogen and R5 is methyl.
28. A process according to claim 1, 2 or 3 wherein R1 is 5-COOCH3, R2 is hydrogen, R6 is hydrogen, R3 is methyl, R4 is OCH3 and R5 is methyl.
29. A process according to claim 1, 2 or 3 wherein R1 is 5-COCH3, R2 is hydrogen, R6 is hydrogen, R3 is methyl, R4 is OCH3 and R5 is methyl.
30. A process according to claim 1, 2 or 3 wherein R1 is 5-OCH3, R2 is hydrogen, R6 is hydrogen, R3 is hydrogen, R4 is OCH3 and R5 is methyl.
31. A process according to claim 1, 2 or 3 wherein R1 is 5-OCH3, R2 is hydrogen, R6 is hydrogen, R3 is methyl, R4 is OCH3 and R5 is methyl.
32. A process according to claim 1, 2 or 3 wherein R1 is 5-CH3, R2 is hydrogen, R6 is hydrogen, R3 is methyl, R4 is OCH3 and R5 is methyl.
33. A process according to claim 1, 2 or 3 wherein R1 is hydrogen, R2 is hydrogen, R6 is hydrogen, R3 is methyl, R4 is OCH3 and R5 is methyl.
34. A process according to claim 1, 2 or 3 wherein R1 is 5-Cl, R2 is hydrogen, R6 is hydrogen, R3 is methyl, R4 is OCH3 and R5 is methyl.
35. A process for preparing 2-[2-(3,4-dimethyl)-pyridylmethylsulfinyl]-(5-acetyl-6-methyl)-benzimidazole which comprises oxidizing 2-[2-(3,4-dimethyl)-pyridylmethylthio]-(5-acetyl-6-methyl)-benzimidazole with m-chloro-perbenzoic acid.
36. The compound 2-[2-(3,4-dimethyl)-pyridylmethylsulfinyl]-(5-acetyl-6-methyl)-benzimidazole when prepared by a process according to claim 35 or an obvious chemical equivalent thereof.
37. A process for preparing 2-[2-(3,5-dimethyl)-pyridylmethylsulfinyl]-(4,6-dimethyl)-benzimidazole which comprises oxidizing 2-[2-(3,5-dimethyl)-pyridylmethylthio]-(4,6-dimethyl)-benzimidazole with m-chloroperbenzoic acid.
38. The compound 2-[2-(3,5-dimethyl)-pyridylmethylsulfinyl]-(4,6-di-methyl)-benzimidazole when prepared by a process according to claim 37 or an obvious chemical equivalent thereof.
39. A process for preparing 2-[2-(4,5-dimethyl)-pyridylmethylsulfinyl]-(5-carbomethoxy)-benzimidazole which comprises oxidizing 2-[2-(4,5-dimethyl)-pyridylmethylthio]-(5-carbomethoxy)-benzimidazole with m-chloroperbenzoic acid.
40. The compound 2-[2-(4,5-dimethyl)-pyridylmethylsulfinyl]-(5-carbo-methoxy)-benzimidazole when prepared by a process according to claim 39 or an obvious chemical equivalent thereof.
41. A process for preparing 2-[2-(4,5-dimethyl)-pyridylmethylsulfinyl]-(5-acetyl-6-methyl)-benzimidazole which comprises oxidizing 2-[2-(4,5-di-methyl)-pyridylmethylthio]-(5-acetyl-6-methyl)-benzimidazole with m-chloro-perbenzoic acid.
42. The compound 2-[2-(4,5-dimethyl)-pyridylmethylsulfinyl]-(5-acetyl-6-methyl)-benzimidazole when prepared by a process according to claim 41 or an obvious chemical equivalent thereof.
43. A process for preparing 2-[2-(4,5-dimethyl)-pyridylmethylsulfinyl]-(5-carbomethoxy-6-methyl)-benzimidazole which comprises oxidizing 2-[2-(4,5-dimethyl)-pyridylmethylthio]-(5-carbomethoxy-6-methyl)-benzimidazole with m-chloroperbenzoic acid.
44. The compound 2-[2-(4,5-dimethyl)-pyridylmethylsulfinyl]-(5-carbo-methoxy-6-methyl)-benzimidazole when prepared by a process according to claim 43 or an obvious chemical equivalent thereof.
45. A process for preparing 2-[2-(3,4-dimethyl)-pyridylmethylsulfinyl]-(5-carbomethoxy-6-methyl)-benzimidazole which comprises oxidizing 2-[2-(3,4-dimethyl)-pyridylmethylthio]-(5-carbomethoxy-6-methyl)-benzimidazole with m-chloroperbenzoic acid.
46. The compound 2-[2-(3,4-dimethyl)-pyridylmethylsulfinyl]-(5-carbo-methoxy-6-methyl)-benzimidazole when prepared by a process according to claim 45 or an obvious chemical equivalent thereof.
47. A process for preparing 2-[2-(3,5-dimethyl)-pyridylmethylsulfinyl]-(5-acetyl-6-methyl)-benzimidazole which comprises reacting 2-[Li-methyl-sulfinyl]-(5-acetyl-6-methyl)-benzimidazole with 2-chloro-(3,5-dimethyl)-pyridine.
48. The compound 2-[2-(3,5-dimethyl)-pyridylmethylsulfinyl]-(5-acetyl-6-methyl)-benzimidazole when prepared by a process according to claim 47 or an obvious chemical equivalent thereof.
49. A process for preparing 2-[2-(3,4,5-trimethyl)-pyridylmethylsul-finyl]-(5-acetyl-6-methyl)-benzimidazole which comprises oxidizing 2-[2-(3,4,5-trimethyl)-pyridylmethylthio]-(5-acetyl-6-methyl)-benzimidazole with m-chloroperbenzoic acid.
50. A process according to claim 49 wherein the 2-[2-(3,4,5-trimethyl)-pyridylmethylthio]-(5-acetyl-6-methyl)-benzimidazole is obtained by reacting 2-[2-(3,4,5-trimethyl)-pyridylmethylthio] formic acid with o-(5-acetyl-6-methyl)-phenylenediamine.
51. The compound 2-[2-(3,4,5-trimethyl)-pyridylmethylsulfinyl]-(5-acetyl-6-methyl)-benzimidazole when prepared by a process according to claim 49 or 50 or an obvious chemical equivalent thereof.
52. A process for preparing 2-[2-(4-methoxy)-pyridylmethylsulfinyl]-(5-acetyl-6-methyl)-benzimidazole which comprises oxidizing 2-[2-(4-methoxy)-pyridylmethylthio]-(5-acetyl-6-methyl)-benzimidazole with m-chloroperbenzoic acid.
53. The compound 2-[2-(4-methoxy)-pyridylmethylsulfinyl]-(5-acetyl-6-methyl)-benzimidazole when prepared by a process according to claim 52 or an obvious chemical equivalent thereof.
54. A process for preparing 2-[2-(4-methoxy)-pyridylmethylsulfinyl]-(4,6-dimethyl)-benzimidazole which comprises oxidizing 2-[2-(4-methoxy)-pyridylmethylthio]-(4,6-dimethyl)-benzimidazole with m-chloroperbenzoic acid.
55. The compound 2-[2-(4-methoxy)-pyridylmethylsulfinyl]-(4,6-dimethyl)-benzimidazole when prepared by a process according to claim 54 or an obvious chemical equivalent thereof.
56. A process for preparing 2-[2-(3,5-dimethyl-4-methoxy)-pyridylmethyl-sulfinyl]-(5-acetyl-6-methyl)-benzimidazole which comprises oxidizing 2-[2-(3,5-dimethyl-4-methoxy)-pyridylmethylthio]-(5-acetyl-6-methyl)-benzimidazole with m-chloroperbenzoic acid.
57. The compound 2-[2-(3,5-dimethyl-4-methoxy)-pyridylmethylsulfinyl]-(5-acetyl-6-methyl)-benzimidazole when prepared by a process according to claim 56 or an obvious chemical equivalent thereof.
58. A process for preparing 2-[2-(3,5-dimethyl)-pyridylmethylsulfinyl]-(5-carbomethoxy-6-methyl)-benzimidazole which comprises oxidizing 2-[2-(3,5-dimethyl)-pyridylmethylthio]-(5-carbomethoxy-6-methyl)-benzimidazole with m-chlorobenzoic acid.
59. The compound 2-[2-(3,5-dimethyl)-pyridylmethylsulfinyl]-(5-carbo-methoxy-6-methyl)-benzimidazole when prepared by a process according to claim 58 or an obvious chemical equivalent thereof.
60. A process for preparing 2-[2-(3,4,5-trimethyl)-pyridylmethylsul-finyl]-(5-carbomethoxy-6-methyl)-benzimidazole which comprises oxidizing 2-[2-(3,4,5-trimethyl)-pyridylmethylthio]-(5-carbomethoxy-6-methyl)-benzimi-dazole with m-chlorobenzoic acid.
61. The compound 2-[2-(3,4,5-trimethyl)-pyridylmethylsulfinyl]-(5-carbomethoxy-6-methyl)-benzimidazole when prepared by a process according to claim 60 or an obvious chemical equivalent thereof.
62. A process for preparing 2-[2-(4-methoxy)-pyridylmethylsulfinyl]-(5-carbomethoxy-6-methyl)-benzimidazole which comprises oxidizing 2-[2-(4-methoxy-pyridylmethylthio]-(5-carbomethoxy-6-methyl)-benzimidazole with m-chlorobenzoic acid.
63. The compound 2-[2-(4-methoxy)-pyridylmethylsulfinyl]-(5-carbo-methoxy-6-methyl)-benzimidazole when prepared by a process according to claim 62 or an obvious chemical equivalent thereof.
64. A process for preparing 2-[2-(4-ethoxy)-pyridylmethylsulfinyl]-(5-carbomethoxy-6-methyl)-benzimidazole which comprises oxidizing 2-[2-(4-ethoxy}-pyridylmethylthio]-(5-carbomethoxy-6-methyl)-benzimidzole with m-chlorobenzoic acid.
65. The compound 2-[2-(4-ethoxy)-pyridylmethylsulfinyl]-(5-carbomethoxy-6-methyl)-benzimidazole when prepared by a process according to claim 64 or an obvious chemical equivalent thereof.
66. A process for preparing 2-[2-(3-methyl-4-methoxy)-pyridylmethyl-sulfinyl]-(5-carbomethoxy-6-methyl)-benzimidazole which comprises oxidizing 2-[2-(3-methyl-4-methoxy)-pyridylmethylthio]-(5-carbomethoxy-6-methyl)-benzimidazole with m-chlorobenzoic acid.
67. The compound 2-[2-(3-methyl-4-methoxy)-pyridylmethylsulfinyl]-(5-carbomethoxy-6-methyl)-benzimidazole when prepared by a process according to
claim 68 or an obvious chemical equivalent thereof.

68. A process for preparing 2-[2-(3,5-dimethyl-4-methoxy)-pyridyl-methylsulfinyl]-(5-carbomethoxy-6-methyl)-benzimidazole which comprises oxidizing 2-[2-(3,5-dimethyl-4-methoxy)pyridylmethylthio]-(5-carbomethoxy-6-methyl)-benzimidazole with m-chlorobenzoic acid.
69. The compound 2-[2-(3,5-dimethyl-4-methoxy)-pyridylmethylsulfinyl]-(5-carbomethoxy-6-methyl)-benzimidazole when prepared by a process according to claim 68 or an obvious chemical equivalent thereof.
70. A process for preparing 2-[2-(4-methoxy-5-methyl)-pyridylmethyl-sulfinyl]-(5-carbomethoxy-6-methyl)-benzimidazole which comprises oxidizing 2-[2-(4-methoxy-5-methyl)-pyridylmethylthio]-(5-carbomethoxy-6-methyl)-benzimidazole with m-chlorobenzoic acid.
71. The compound 2-[2-(4-methoxy-5-methyl)-pyridylmethylsulfinyl]-(5-carbomethoxy-6-methyl)-benzimidazole when prepared by a process according to claim 70 or an obvious chemical equivalent thereof.
72. A process for preparing 2-[2-(3,5-dimethyl)-pyridylmethylsulfinyl]-(5-carbomethoxy)-benzimidazole which comprises oxidizing 2-[2-(3,5-dimethyl)-pyridylmethylthio]-(5-carbomethoxy)-benzimidazole with m-chlorobenzoic acid.
73. The compound 2-[2-(3,5-dimethyl)-pyridylmethylsulfinyl]-(5-carbo-methoxy)-benzimidazole when prepared by a process according to claim 72 or an obvious chemical equivalent thereof.
74. A process for preparing 2-[2-(3,5-dimethyl-4-methoxy)-pyridylmethyl-sulfinyl]-(5-carbomethoxy)-benzimidazole which comprises oxidizing 2-[2-(3,5-dimethyl-4-methoxy)-pyridylmethylthio]-(5-carbomethoxy)-benzimidazole with m-chlorobenzoic acid.
75. The compound 2-[2-(3,5-dimethyl-4-methoxy)-pyridylmethylsulfinyl]-(5-carbomethoxy)-benzimidazole when prepared by a process according to claim 74 or an obvious chemical equivalent thereof.
76. A process for preparing 2-[2-(3,5-dimethyl-4-methoxy)-pyridylmethyl-sulfinyl]-(5-acetyl)-benzimidazole which comprises oxidizing 2-[2-(3,5-dimethyl-4-methoxy)-pyridylmethylthio]-(5-acetyl)-benzimidazole with m-chlorobenzoic acid.
77. The compound 2-[2-(3,5-dimethyl-4-methoxy)-pyridylmethylsulfinyl]-(5-acetyl)-benzimidazole when prepared by a process according to claim 76 or an obvious chemical equivalent thereof.
78. A process for preparing 2-[2-(4-methoxy-5-methyl)-pyridylmethyl-sulfinyl]-(5-methoxy)-benzimidazole which comprises oxidizing 2-[2-(4-methoxy-5-methyl)-pyridylmethylthio]-(5-methoxy)-benzimidazole with m-chloro-benzoic acid.
79. The compound 2-[2-(4-methoxy-5-methyl)-pyridylmethylsulfinyl]-(5-methoxy)-benzimidazole when prepared by a process according to claim 78 or an obvious chemical equivalent thereof.
80. A process for preparing 2-[2-(3,5-dimethyl-4-methoxy)-pyridyl-methylsulfinyl]-(5-methoxy)-benzimidazole which comprises oxidizing 2-[2-(3,5-dimethyl-4-methoxy)-pyridylmethylthio]-(5-methoxy)-benzimidazole with m-chlorobenzoic acid.
81. A process according to claim 80 wherein the 2-[2-(3,5-dimethyl-4-methoxy)-pyridylmethylthio]-(5-methoxy)-benzimidazole is obtained by reacting 5-methoxy-2-mercaptobenzimidazole with 2-chloromethyl-3,5-dimethyl-4-methoxy-pyridine.
82. A process according to claim 80 wherein the 2-[2-(3,5-dimethyl-4-methoxy)-pyridylmethylthio]-(5-methoxy)-benzimidazole is obtained by reacting 2-[2-(3,5-dimethyl-4-methoxy-pyridylmethylthio] formic acid with o-(4-methoxy)-phenylene-diamine.
83. The compound 2-[2-(3,5-dimethyl-4-methoxy)-pyridylmethylsulfinyl]-(5-methoxy)-benzimidazole when prepared by a process according to claim 80, 81 or 82 or an obvious chemical equivalent thereof.
84. A process for preparing 2-[2-(3,5-dimethyl-4-methoxy)-pyridyl-methylsulfinyl]-(5-methyl)-benzimidazole which comprises oxidizing 2-[2-(3,5-dimethyl-4-methoxy)-pyridylmethylthio]-(5-methyl)-benzimidazole with m-chloro-benzoic acid.
85. The compound 2-[2-(3,5-dimethyl-4-methoxy)-pyridylmethylsulfinyl]-(5-methyl)-benzimidazole when prepared by a process according to claim 84 or an obvious chemical equivalent thereof.
86. A process for preparing 2-[2-(3,5-dimethyl-4-methoxy)-pyridyl-methylsulfinyl]-benzimidazole which comprises oxidizing 2-[2-(3,5-dimethyl-4-methoxy)-pyridylmethylthio]-benzimidazole with m-chlorobenzoic acid.
87. The compound 2-[2-(3,5-dimethyl-4-methoxy)-pyridylmethylsulfinyl]-benzimidazole when prepared by a process according to claim 86 or an obvious chemical equivalent thereof.
88. A process for preparing 2-[2-(3,5-dimethyl-4-methoxy)-pyridyl-methylsulfinyl]-(5-chloro)-benzimidazole which comprises oxidizing 2-[2-(3,5-dimethyl-4-methoxy)-pyridylmethylthio]-(5-chloro-benzimidazole with m-chlorobenzoic acid.
89. The compound 2-[2-(3,5-dimethyl-4-methoxy)-pyridylmethylsulfinyl]-(5-chloro)-benzimidazole when prepared by a process according to claim 88 or an obvious chemical equivalent thereof.
CA325,188A 1978-04-14 1979-04-09 2-pyridylmethylsulfinyl-benzimidazole compounds Expired CA1127158A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CA386,943A CA1129417A (en) 1978-04-14 1981-09-29 Gastric acid secretion inhibiting substituted 2-(2- benzimidazolyl)-pyridines, their preparation, pharmaceutical preparations containing same, and method for inhibiting gastricacid secretion

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
SE7804231-4 1978-04-14
SE7804231A SE7804231L (en) 1978-04-14 1978-04-14 Gastric acid secretion

Publications (1)

Publication Number Publication Date
CA1127158A true CA1127158A (en) 1982-07-06

Family

ID=20334608

Family Applications (1)

Application Number Title Priority Date Filing Date
CA325,188A Expired CA1127158A (en) 1978-04-14 1979-04-09 2-pyridylmethylsulfinyl-benzimidazole compounds

Country Status (25)

Country Link
US (3) US4255431A (en)
EP (1) EP0005129B1 (en)
JP (2) JPS6034956B2 (en)
AT (2) AT389995B (en)
BG (1) BG61492B2 (en)
CA (1) CA1127158A (en)
CS (1) CS261851B2 (en)
CY (1) CY1232A (en)
DD (1) DD142882A5 (en)
DE (1) DE2960293D1 (en)
DK (1) DK150510C (en)
FI (1) FI65067C (en)
HK (1) HK15284A (en)
HU (1) HU179022B (en)
IE (1) IE48370B1 (en)
LT (1) LT2274B (en)
LU (2) LU88307I2 (en)
MY (1) MY8500074A (en)
NL (2) NL930074I2 (en)
NO (5) NO152216C (en)
NZ (1) NZ190203A (en)
SE (1) SE7804231L (en)
SG (1) SG63383G (en)
SU (4) SU895292A3 (en)
ZA (1) ZA791586B (en)

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995012590A1 (en) 1993-11-04 1995-05-11 Torcan Chemical Ltd. Preparation of omeprazole and lansoprazole and intermediates useful therein
US6077541A (en) * 1997-11-14 2000-06-20 Andrx Pharmaceuticals, Inc. Omeprazole formulation
US6121454A (en) * 1997-05-06 2000-09-19 Pdi-Research Laboratories, Inc. Synthesis of pharmaceutically useful pyridine derivatives
US6174548B1 (en) 1998-08-28 2001-01-16 Andrx Pharmaceuticals, Inc. Omeprazole formulation
US6437139B1 (en) 1997-05-06 2002-08-20 Pdi-Research Laboratories, Inc. Synthesis of pharmaceutically useful pyridine derivatives
US6733778B1 (en) 1999-08-27 2004-05-11 Andrx Pharmaceuticals, Inc. Omeprazole formulation
US7129358B2 (en) 2001-02-02 2006-10-31 Teva Pharmaceutical Industries Ltd. Processes for the production of substituted 2-(2-pyridylmethyl) sulfinyl-1H-benzimidazoles
WO2010134099A1 (en) 2009-05-21 2010-11-25 Cadila Healthcare Limited One pot process for preparing omeprazole and related compounds
WO2013108068A1 (en) 2012-01-21 2013-07-25 Jubilant Life Sciences Limited Process for the preparation of 2-pyridinylmethylsulfinyl benzimidazoles, their analogs and optically active enantiomers

Families Citing this family (361)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4359465A (en) * 1980-07-28 1982-11-16 The Upjohn Company Methods for treating gastrointestinal inflammation
CH644116A5 (en) * 1980-08-21 1984-07-13 Hoffmann La Roche IMIDAZOLE DERIVATIVES.
IL66340A (en) * 1981-08-13 1986-08-31 Haessle Ab Pharmaceutical compositions comprising pyridylmethyl-thiobenzimidazole derivatives,certain such novel derivatives and their preparation
US4472409A (en) * 1981-11-05 1984-09-18 Byk Gulden Lomberg Chemische Fabrik Gesellschaft Mit Beschrankter Haftung 2-Pyridylmethyl thio(sulfinyl)benzimidazoles with gastric acid secretion inhibiting effects
JPS58135881A (en) * 1981-11-05 1983-08-12 ビク−グルデン・ロムベルク・ヘミツシエ・フアブリク・ゲゼルシヤフト・ミト・ベシユレンクテル・ハフツング Substituted benzimidazoles, manufacture and use and medicine
DE3216843C2 (en) * 1982-05-05 1986-10-23 Ludwig Heumann & Co GmbH, 8500 Nürnberg 3-Thiomethyl-pyridine derivatives, processes for their preparation and pharmaceuticals containing these compounds
SE8204879D0 (en) * 1982-08-26 1982-08-26 Haessle Ab NOVEL CHEMICAL INTERMEDIATES
SE8300736D0 (en) * 1983-02-11 1983-02-11 Haessle Ab NOVEL PHARMACOLOGICALLY ACTIVE COMPOUNDS
SE8301182D0 (en) * 1983-03-04 1983-03-04 Haessle Ab NOVEL COMPOUNDS
IL71664A (en) * 1983-05-03 1987-11-30 Byk Gulden Lomberg Chem Fab Fluoroalkoxy compounds,process for their preparation and pharmaceutical compositions containing the same
HU193408B (en) * 1983-05-03 1987-10-28 Byk Gulden Lomberg Chem Fqb Process for production of new tree-cycle compounds
CA1259070A (en) * 1983-07-01 1989-09-05 Upjohn Company (The) Substituted 2-¬monoannelated(3,4-,4,5-, and 5,6-)- pyridylalkylenesulfinyl|-benzimidazoles
US5077407A (en) * 1983-07-01 1991-12-31 The Upjohn Company Substituted 2-[monoannelated (3,4-,4,5-, and 5,6-) pyridylalkylenesulfinyl]benzimidazoles
DE3333314A1 (en) * 1983-09-15 1985-03-28 Hoechst Ag, 6230 Frankfurt SUBSTITUTED PYRIDO (1,2-C) IMIDAZO (1,2-A) BENZIMIDAZOLES, METHOD FOR THE PRODUCTION THEREOF, THEIR USE AND PHARMACEUTICAL PREPARATIONS BASED ON THESE COMPOUNDS
US4663347A (en) 1983-10-31 1987-05-05 Merck Frosst Canada, Inc. Benzofuran 2-carboxylic acid esters useful as inhibitors of leukotriene biosynthesis
US4575554A (en) * 1983-12-05 1986-03-11 The Upjohn Company Substituted 2-pyridylmethylthio- and sulfinyl-benzimidazoles as gastric antisecretory agents
ZW4585A1 (en) * 1984-04-19 1985-11-20 Hoffmann La Roche Imidazole derivatives
SE8403179D0 (en) * 1984-06-13 1984-06-13 Haessle Ab NEW COMPOUNDS
IL75400A (en) * 1984-06-16 1988-10-31 Byk Gulden Lomberg Chem Fab Dialkoxypyridine methyl(sulfinyl or sulfonyl)benzimidazoles,processes for the preparation thereof and pharmaceutical compositions containing the same
CA1341314C (en) * 1984-07-06 2001-11-06 David Cox Derivatives of benzimidazole, benzothiazole and benzoxazole
SE8404065D0 (en) * 1984-08-10 1984-08-10 Haessle Ab NOVEL BIOLOGICALLY ACTIVE COMPOUNDS
JPS6150978A (en) * 1984-08-16 1986-03-13 Takeda Chem Ind Ltd Pyridine derivative and preparation thereof
JPS6150979A (en) * 1984-08-16 1986-03-13 Takeda Chem Ind Ltd Pyridine derivative and preparation thereof
US4619997A (en) * 1984-09-06 1986-10-28 The Upjohn Company Substituted 2-pyridylmethylthio and sulfinyl-benzimidazoles as gastric antisecretory agents
KR890000387B1 (en) * 1984-09-24 1989-03-16 디 엎존 캄파니 N-substituted derivatives of 2-(pyridylalkene-sulfinyl)benzimidazoles and process for the preparation thereof
SE8405588D0 (en) * 1984-11-08 1984-11-08 Haessle Ab NEW COMPOUNDS
EP0187977B1 (en) * 1984-12-18 1990-08-29 Otsuka Pharmaceutical Co., Ltd. Tetrahydroquinoline derivatives, process for preparing the same and anti-peptic ulcer compositions containg the same
FI861772A (en) * 1985-05-07 1986-11-08 Chemie Linz Ag THEN THEN (2,3-D) IMIDED INSULATED FOR THE FRAME FRAMEWORK.
US5869513A (en) * 1985-05-24 1999-02-09 G. D. Searle & Co. 2- (1H-benzimidazol-2-ylsulfinyl)methyl!benzenamines
EP0204215B1 (en) 1985-05-24 1993-08-11 G.D. Searle & Co. 2-[(1H-benzimidazol-2-ylsulfinyl)methyl]-benzenamines
CA1309557C (en) 1985-06-18 1992-10-27 Robert N. Young Leukotriene antagonists
US4738975A (en) * 1985-07-02 1988-04-19 Takeda Chemical Industries, Ltd. Pyridine derivatives, and use as anti-ulcer agents
AR243167A1 (en) 1985-08-24 1993-07-30 Hoechst Ag Substituted toluidines, process for their preparation, pharmaceutical compositions containing them and their use as gastric secretion inhibitors
JPS6261978A (en) * 1985-09-12 1987-03-18 Otsuka Pharmaceut Co Ltd 5-fluoro-1h-benzimidazole derivative
SE8505112D0 (en) * 1985-10-29 1985-10-29 Haessle Ab NOVEL PHARMACOLOGICAL COMPOUNDS
US5433959A (en) 1986-02-13 1995-07-18 Takeda Chemical Industries, Ltd. Stabilized pharmaceutical composition
US6749864B2 (en) * 1986-02-13 2004-06-15 Takeda Chemical Industries, Ltd. Stabilized pharmaceutical composition
CA1327010C (en) * 1986-02-13 1994-02-15 Tadashi Makino Stabilized solid pharmaceutical composition containing antiulcer benzimidazole compound and its production
DE3777855D1 (en) 1986-02-20 1992-05-07 Hoechst Ag SUBSTITUTED THIENOIMIDAZOLE DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF, PHARMACEUTICAL PREPARATIONS CONTAINING THE SAME AND THEIR USE AS AN INGESTIC ACID INHIBITOR.
WO1987005296A1 (en) * 1986-03-07 1987-09-11 Pfizer Inc. 2-[(2-pyridyl)methylsulfinyl]thienoimidazoles and related compounds as antiulcer agents
EP0239306B1 (en) 1986-03-27 1993-06-02 Merck Frosst Canada Inc. Tetrahydrocarbazole esters
GB2189698A (en) * 1986-04-30 1987-11-04 Haessle Ab Coated omeprazole tablets
GB2189699A (en) * 1986-04-30 1987-11-04 Haessle Ab Coated acid-labile medicaments
US4687775A (en) * 1986-07-17 1987-08-18 G. D. Searle & Co. 2-[(Imidazo[1,2-a]pyridinylmethyl)sulfinyl]-1H-benzimidazoles
US4772619A (en) * 1986-07-17 1988-09-20 G. D. Searle & Co. [(1H-benzimidazol-2-ylsulfinyl)methyl]-2-pyridinamines
US4721718A (en) * 1986-08-18 1988-01-26 G. D. Searle & Co. 2-[(imidazo[1,2-a]pyridin-3-ylmethyl)sulfinyl]-1H-benzimidazoles useful in the treatment and prevention of ulcers
CA1256109A (en) * 1986-09-10 1989-06-20 Franz Rovenszky Process for the preparation of derivatives of 4, 5-dihydrooxazoles
SE8604566D0 (en) * 1986-10-27 1986-10-27 Haessle Ab NOVEL COMPUNDS
EP0786461A1 (en) * 1986-11-13 1997-07-30 Eisai Co., Ltd. Pyridine derivatives, pharmaceutical compositions comprising the same, the use of the same for the manufacture of medicaments having therapeutic or preventative value, and a process for preparing the same
FI90544C (en) * 1986-11-13 1994-02-25 Eisai Co Ltd Process for Preparation as Drug Useful 2-Pyridin-2-yl-methylthio- and sulfinyl-1H-benzimidazole derivatives
SE8604998D0 (en) 1986-11-21 1986-11-21 Haessle Ab NOVEL PHARMACOLOGICAL COMPOUNDS
NZ222495A (en) 1986-11-21 1991-04-26 Haessle Ab Benzimidazole derivatives and pharmaceutical compositions
DE3639926A1 (en) * 1986-11-22 1988-06-01 Hoechst Ag SUBSTITUTED THIENOIMIDAZOLTOLUIDINE DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF, PHARMACEUTICAL PREPARATIONS CONTAINING IT AND THEIR USE AS AN INGESTIC ACID INHIBITOR
FI91754C (en) * 1986-12-02 1994-08-10 Tanabe Seiyaku Co An analogous method for preparing an imidazole derivative useful as a medicament
JPS63230633A (en) * 1987-03-19 1988-09-27 Nippon Chemiphar Co Ltd Protecting agent for gastroenteric cell
DE3719783A1 (en) * 1987-06-13 1988-12-22 Hoechst Ag METHOD FOR PRODUCING 5-PHENYLSULFINYL-1H-2- (METHOXYCARBONYLAMINO) - BENZIMIDAZOLE
JP2718945B2 (en) * 1987-06-17 1998-02-25 エーザイ株式会社 Pyridine derivative and therapeutic agent for ulcer containing the same
FI96860C (en) * 1987-06-17 1996-09-10 Eisai Co Ltd An analogous method for preparing a pyridine derivative for use as a medicament
DE3723327A1 (en) * 1987-07-15 1989-02-02 Hoechst Ag SUBSTITUTED THIENOIMIDAZOLE DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF, PHARMACEUTICAL PREPARATIONS CONTAINING THEM AND THEIR USE AS ANTI-ACIDIC SECRETION AGENT, ANTI-STAGE AGENT AND AS A MEDICINE AGAINST INTESTINALS
DK171989B1 (en) * 1987-08-04 1997-09-08 Takeda Chemical Industries Ltd Process for the preparation of 2- (2-pyridylmethylsulfinyl) benzimidazoles
US5124158A (en) * 1988-06-30 1992-06-23 The Upjohn Company Transdermal antisecretory agents for gastrointestinal disease
US5223515A (en) * 1988-08-18 1993-06-29 Takeda Chemical Industries, Ltd. Injectable solution containing a pyridyl methylsulfinylbenzimidazole
KR900701270A (en) * 1988-08-23 1990-12-01 안데르스 베딘 Treatment of glaucoma and related disorders in human eyes with pyridinylmethyl (sulfinyl or thio) benzimidazole
US5075323A (en) * 1988-08-24 1991-12-24 Aktiebolaget Hassle Compounds including omeprazole in the treatment of glaucoma
EP0436025A4 (en) * 1988-09-20 1991-09-11 Hisamitsu Pharmaceutical Co. Inc. Novel dibenz b,e)oxepin derivatives
AT391693B (en) * 1988-11-15 1990-11-12 Cl Pharma METHOD FOR PRODUCING 3-5-DIMETHYL-4METHOXYPYRIDINE DERIVATIVES AND NEW INTERMEDIATE PRODUCT THEREFOR
SE8804629D0 (en) 1988-12-22 1988-12-22 Ab Haessle NEW THERAPEUTICALLY ACTIVE COMPOUNDS
SE8804628D0 (en) 1988-12-22 1988-12-22 Ab Haessle NEW COMPOUNDS
IE64199B1 (en) * 1988-12-22 1995-07-12 Haessle Ab Compound with gastric acid inhibitory effect and process for its preparation
JP2694361B2 (en) * 1989-02-09 1997-12-24 アストラ アクチエボラグ Antibacterial agent
GB2239453A (en) * 1989-11-27 1991-07-03 Haessle Ab Omeprazole
US5049674A (en) * 1989-12-20 1991-09-17 Aktiebolaget Hassle Therapeutically active fluoro substituted benzimidazoles
US5274099A (en) * 1989-12-20 1993-12-28 Aktiebolaget Hassle Therapeutically active fluoro substituted benzimidazoles
US4965269A (en) * 1989-12-20 1990-10-23 Ab Hassle Therapeutically active chloro substituted benzimidazoles
KR930000861B1 (en) * 1990-02-27 1993-02-08 한미약품공업 주식회사 Omeprazole rectal composition
PL172133B1 (en) 1990-04-04 1997-08-29 Chiron Corp Method of creating a combination of antigenes of viral hematitis c (hcv) and method of detecting antibodies against c (hcv)
SE9002043D0 (en) 1990-06-07 1990-06-07 Astra Ab IMPROVED METHOD FOR SYNTHESIS
CA2083606C (en) * 1990-06-20 2001-08-21 Arne Elof Brandstrom Dialkoxy-pyridinyl-benzimidazole derivatives, process for their preparation and their pharmaceutical use
SE9002206D0 (en) 1990-06-20 1990-06-20 Haessle Ab NEW COMPOUNDS
US5061805A (en) * 1990-08-10 1991-10-29 Reilly Industries, Inc. Process for preparing 2-methyl-3,5-dialkylpyridines by dealkylation with sulfur
CA2052698A1 (en) * 1990-10-11 1992-04-12 Roger G. Berlin Treatment of peptic ulcer
EP0480716A1 (en) 1990-10-12 1992-04-15 Merck Frosst Canada Inc. Saturated hydroxyalkylquinoline acids as leukotriene antagonists
CA2053527C (en) * 1990-10-17 2002-03-12 Takashi Sohda Pyridine derivatives, their production and use
ES2026761A6 (en) * 1990-10-31 1992-05-01 Genesis Para La Investigacion A process for the preparation of omeprazol.
NZ244301A (en) * 1991-09-20 1994-08-26 Merck & Co Inc Preparation of 2-pyridylmethylsulphinylbenzimidazole and pyridoimidazole derivatives from the corresponding sulphenyl compounds
FR2692146B1 (en) * 1992-06-16 1995-06-02 Ethypharm Sa Stable compositions of gastro-protected omeprazole microgranules and process for obtaining them.
WO1994001107A1 (en) * 1992-07-08 1994-01-20 Monsanto Company Benzimidazoles for alleviating stomach ulcers in swine
US5589491A (en) * 1992-07-28 1996-12-31 Astra Aktiebolag Injection and injection kit containing omeprazole and its analogs
SE9301830D0 (en) * 1993-05-28 1993-05-28 Ab Astra NEW COMPOUNDS
US6875872B1 (en) 1993-05-28 2005-04-05 Astrazeneca Compounds
SE9302395D0 (en) * 1993-07-09 1993-07-09 Ab Astra NEW PHARMACEUTICAL FORMULATION
SE9302396D0 (en) * 1993-07-09 1993-07-09 Ab Astra A NOVEL COMPOUND FORM
US5410054A (en) * 1993-07-20 1995-04-25 Merck Frosst Canada, Inc. Heteroaryl quinolines as inhibitors of leukotriene biosynthesis
TW280770B (en) 1993-10-15 1996-07-11 Takeda Pharm Industry Co Ltd
EP0729957A4 (en) * 1993-10-29 1996-12-27 Yoshitomi Pharmaceutical Pyridine compound and medicinal use thereof
US5502195A (en) * 1993-11-04 1996-03-26 Slemon; Clarke Sulfoxide-carboxylate intermediates of omeprazole and lansoprazole
KR0142815B1 (en) * 1994-12-02 1998-07-15 정도언 Novel 5-pyrrolyl-o-halogeno-2-pyridyl methylsulfinylbenzimidazole derivatlves
KR0179401B1 (en) * 1994-02-28 1999-03-20 송택선 Novel 5-pyrrolyl-2-pyridylmethylsulfanilbenzimidazole derivatives
WO1995029897A1 (en) * 1994-04-29 1995-11-09 G.D. Searle & Co. METHOD OF USING (H+/K+) ATPase INHIBITORS AS ANTIVIRAL AGENTS
SE9402431D0 (en) * 1994-07-08 1994-07-08 Astra Ab New tablet formulation
MX9600857A (en) * 1994-07-08 1997-06-28 Astra Ab Multiple unit tableted dosage form i.
SE504459C2 (en) * 1994-07-15 1997-02-17 Astra Ab Process for the preparation of substituted sulfoxides
GB9423968D0 (en) * 1994-11-28 1995-01-11 Astra Ab Resolution
GB9423970D0 (en) * 1994-11-28 1995-01-11 Astra Ab Oxidation
SE9500422D0 (en) * 1995-02-06 1995-02-06 Astra Ab New oral pharmaceutical dosage forms
SE9500478D0 (en) * 1995-02-09 1995-02-09 Astra Ab New pharmaceutical formulation and process
JP3015702B2 (en) * 1995-02-21 2000-03-06 株式会社アラクス Imidazole derivatives, their pharmaceutically acceptable acid addition salts, their production, and antiulcer agents containing them as active ingredients
JP3046924B2 (en) * 1995-03-27 2000-05-29 株式会社アラクス Imidazoline derivatives or their possible tautomers, methods for their preparation and wound treatments containing them as active ingredients
US5708017A (en) * 1995-04-04 1998-01-13 Merck & Co., Inc. Stable, ready-to-use pharmaceutical paste composition containing proton pump inhibitors
HRP960232A2 (en) * 1995-07-03 1998-02-28 Astra Ab A process for the optical purification of compounds
US5686588A (en) * 1995-08-16 1997-11-11 Yoo; Seo Hong Amine acid salt compounds and process for the production thereof
US5824339A (en) * 1995-09-08 1998-10-20 Takeda Chemical Industries, Ltd Effervescent composition and its production
DE69628444T2 (en) * 1995-09-21 2004-05-06 Pharma Pass Ii Llc, Irvine ACID CONTAINING PHARMACEUTICAL COMPOSITION CONTAINING ACID, AND METHOD FOR THE PRODUCTION THEREOF
SE521100C2 (en) * 1995-12-15 2003-09-30 Astra Ab Process for the preparation of a benzimidazole compound
KR970032861A (en) * 1995-12-29 1997-07-22 김준웅 Helicobacter pylori removal drug administration method
US6699885B2 (en) 1996-01-04 2004-03-02 The Curators Of The University Of Missouri Substituted benzimidazole dosage forms and methods of using same
US20050054682A1 (en) * 1996-01-04 2005-03-10 Phillips Jeffrey O. Pharmaceutical compositions comprising substituted benzimidazoles and methods of using same
US6645988B2 (en) 1996-01-04 2003-11-11 Curators Of The University Of Missouri Substituted benzimidazole dosage forms and method of using same
US5840737A (en) * 1996-01-04 1998-11-24 The Curators Of The University Of Missouri Omeprazole solution and method for using same
US6489346B1 (en) * 1996-01-04 2002-12-03 The Curators Of The University Of Missouri Substituted benzimidazole dosage forms and method of using same
SE9600070D0 (en) 1996-01-08 1996-01-08 Astra Ab New oral pharmaceutical dosage forms
WO1997029103A2 (en) * 1996-02-06 1997-08-14 Pdi-Research Laboratories, Inc. Synthesis of omeprazole-type pyridine derivatives and intermediates thereof
US6623759B2 (en) 1996-06-28 2003-09-23 Astrazeneca Ab Stable drug form for oral administration with benzimidazole derivatives as active ingredient and process for the preparation thereof
US5625069A (en) * 1996-07-22 1997-04-29 Development Center For Biotechnology Process for preparing 2-cyano-3,5-dimethyl-4-methoxypyridine
US6380222B2 (en) 1996-10-11 2002-04-30 Astrazeneca Ab Use of an H+, K+-atpase inhibitor in the treatment of nasal polyps
TW385306B (en) * 1996-11-14 2000-03-21 Takeda Chemical Industries Ltd Method for producing crystals of benzimidazole derivatives
SE510666C2 (en) * 1996-12-20 1999-06-14 Astra Ab New Crystal Modifications
KR100463031B1 (en) * 1997-05-26 2005-04-06 동아제약주식회사 New preparation method of 5-methoxy-2- [3,5-dimethyl-4-methoxypyridylmethyl) sulfinyl] -1H-benzimidazole
SE9702000D0 (en) * 1997-05-28 1997-05-28 Astra Ab New pharmaceutical formulation
US6747155B2 (en) 1997-05-30 2004-06-08 Astrazeneca Ab Process
SE510650C2 (en) 1997-05-30 1999-06-14 Astra Ab New association
US6051570A (en) * 1997-05-30 2000-04-18 Dr. Reddy's Research Foundation Benzimidazole derivatives as antiulcer agents, process for their preparation and pharmaceutical compositions containing them
SE510643C2 (en) 1997-06-27 1999-06-14 Astra Ab Thermodynamically stable omeprazole sodium form B
CN1169807C (en) * 1997-07-11 2004-10-06 卫材株式会社 Processes for preparation of pyridine derivs.
SI9700186B (en) * 1997-07-14 2006-10-31 Lek, Tovarna Farmacevtskih In Kemicnih Izdelkov, D.D. Novel pharmaceutical preparation with controlled release of active healing substances
WO1999004816A1 (en) 1997-07-25 1999-02-04 Byk Gulden Lomberg Chemische Fabrik Gmbh Proton pump inhibitor in therapeutic combination with antibacterial substances
US6296876B1 (en) 1997-10-06 2001-10-02 Isa Odidi Pharmaceutical formulations for acid labile substances
US7230014B1 (en) * 1997-10-14 2007-06-12 Eisai Co., Ltd. Pharmaceutical formulation comprising glycine as a stabilizer
SE9704183D0 (en) 1997-11-14 1997-11-14 Astra Ab New process
DE19754324A1 (en) * 1997-12-08 1999-06-10 Byk Gulden Lomberg Chem Fab Easily prepared oral dosage forms for acid-labile drugs, especially proton pump inhibitors
DE69831504T2 (en) 1997-12-08 2006-06-14 Altana Pharma Ag ORAL ADMINISTRATIVE FORM CONTAINING A PROTON PUMP INHIBITOR (FOR EXAMPLE, PANTOPRAZOLE)
SE9704869D0 (en) * 1997-12-22 1997-12-22 Astra Ab New pharmaceutical formulaton II
SE9704870D0 (en) * 1997-12-22 1997-12-22 Astra Ab New pharmaceutical formulation I
US6159968A (en) * 1998-01-15 2000-12-12 University Of Cincinnati Activation of chloride channels for correction of defective chloride transport
KR100396431B1 (en) 1998-01-26 2003-09-02 가부시키가이샤 구라레 Method for producing 2-sulfonylpyridine derivatives and method for producing 2-[((2-pyridyl)methyl)thio]-1h-benzimidazole derivatives
US6350876B2 (en) 1998-01-26 2002-02-26 Kuraray Co., Ltd. 4-chloro-3,5-dimethyl-2-sulfonyl pyridines
IT1299198B1 (en) 1998-03-05 2000-02-29 Nicox Sa NITRATED SALTS OF ANTI-ULCER DRUGS
WO1999059544A2 (en) 1998-05-18 1999-11-25 Takeda Chemical Industries, Ltd. Orally disintegrable tablets
US6303787B1 (en) 1998-05-27 2001-10-16 Natco Pharma Limited Intermediates and an improved process for the preparation of Omeprazole employing the said intermediates
ZA9810765B (en) * 1998-05-28 1999-08-06 Ranbaxy Lab Ltd Stable oral pharmaceutical composition containing a substituted pyridylsulfinyl benzimidazole.
WO2000000474A1 (en) * 1998-06-26 2000-01-06 Russinsky Limited Pyridine building blocks as intermediates in the synthesis of pharmaceutically active compounds
SI20019A (en) * 1998-07-13 2000-02-29 LEK, tovarna farmacevtskih in kemi�nih izdelkov, d.d. An improved process for synthesis of 5-methoxy-2-/(4-methoxy-3,5-dimethyl-2-pyridyl)methyl/ sulphynyl-1h-benzimidazol
US6093734A (en) * 1998-08-10 2000-07-25 Partnership Of Michael E. Garst, George Sachs, And Jai Moo Shin Prodrugs of proton pump inhibitors
NZ510180A (en) * 1998-08-10 2002-11-26 Univ California Prodrugs of the pyridyl-methylsulphonyl-benzimidazole type proton pump inhibitors
US6191148B1 (en) * 1998-08-11 2001-02-20 Merck & Co., Inc. Omerazole process and compositions thereof
US6166213A (en) * 1998-08-11 2000-12-26 Merck & Co., Inc. Omeprazole process and compositions thereof
US7041313B1 (en) 1998-08-12 2006-05-09 Altana Pharma Ag Oral administration form for pyridin-2-ylmethylsulfinyl-1H-benzimidazoles
DE19843413C1 (en) * 1998-08-18 2000-03-30 Byk Gulden Lomberg Chem Fab New salt form of pantoprazole
SE9803772D0 (en) 1998-11-05 1998-11-05 Astra Ab Pharmaceutical formulation
WO2000027841A1 (en) * 1998-11-06 2000-05-18 Dong-A Pharmaceutical Co., Ltd. Method of preparing sulfide derivatives
UA72748C2 (en) * 1998-11-10 2005-04-15 Astrazeneca Ab A novel crystalline form of omeprazole
IL142703A (en) 1998-11-10 2006-04-10 Astrazeneca Ab Crystalline form of omeprazole
JP3926936B2 (en) 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
SE9900274D0 (en) 1999-01-28 1999-01-28 Astra Ab New compound
US6852739B1 (en) * 1999-02-26 2005-02-08 Nitromed Inc. Methods using proton pump inhibitors and nitric oxide donors
TWI243672B (en) 1999-06-01 2005-11-21 Astrazeneca Ab New use of compounds as antibacterial agents
WO2000074654A1 (en) 1999-06-07 2000-12-14 Byk Gulden Lomberg Chemische Fabrik Gmbh Novel preparation and administration form comprising an acid-labile active compound
IL130602A0 (en) 1999-06-22 2000-06-01 Dexcel Ltd Stable benzimidazole formulation
US6555139B2 (en) 1999-06-28 2003-04-29 Wockhardt Europe Limited Preparation of micron-size pharmaceutical particles by microfluidization
US6245913B1 (en) 1999-06-30 2001-06-12 Wockhardt Europe Limited Synthetic procedure for 5-methoxy-2-[(4-methoxy-3,5-dimethyl-2-pyridinyl)-methylthio]-IH-benzimidazole hydrochloride and its conversion to omeprazole
US6262085B1 (en) 1999-08-26 2001-07-17 Robert R. Whittle Alkoxy substituted Benzimidazole compounds, pharmaceutical preparations containing the same, and methods of using the same
US6262086B1 (en) 1999-08-26 2001-07-17 Robert R. Whittle Pharmaceutical unit dosage form
US6312723B1 (en) 1999-08-26 2001-11-06 Robert R. Whittle Pharmaceutical unit dosage form
US6316020B1 (en) 1999-08-26 2001-11-13 Robert R. Whittle Pharmaceutical formulations
US6268385B1 (en) 1999-08-26 2001-07-31 Robert R. Whittle Dry blend pharmaceutical formulations
US6780880B1 (en) 1999-08-26 2004-08-24 Robert R. Whittle FT-Raman spectroscopic measurement
KR100712039B1 (en) * 1999-08-26 2007-04-27 에이에이아이파머 인코포레이티드 Alkoxy substituted benzimidazole compounds, pharmaceutical preparations containing the same, and methods of using the same
US6369087B1 (en) 1999-08-26 2002-04-09 Robert R. Whittle Alkoxy substituted benzimidazole compounds, pharmaceutical preparations containing the same, and methods of using the same
US6312712B1 (en) 1999-08-26 2001-11-06 Robert R. Whittle Method of improving bioavailability
EP1595879A3 (en) * 1999-08-26 2010-01-27 aaiPharma Inc. Alkoxy substituted benzimidazole compounds, pharmaceutical preparations containing the same, and methods of using the same
US6326384B1 (en) 1999-08-26 2001-12-04 Robert R. Whittle Dry blend pharmaceutical unit dosage form
KR20020043565A (en) * 1999-08-26 2002-06-10 에이에이아이파머 인코포레이티드 FT-RAMAN spectroscopic measurement of omeprazole isomer ratio in a composition
US6228400B1 (en) 1999-09-28 2001-05-08 Carlsbad Technology, Inc. Orally administered pharmaceutical formulations of benzimidazole derivatives and the method of preparing the same
SE9903831D0 (en) 1999-10-22 1999-10-22 Astra Ab Formulation of substituted benzimidazoles
DE19951960C2 (en) * 1999-10-28 2002-06-27 Gruenenthal Gmbh Process for the preparation of benzimidazole derivatives suitable as ulcer therapeutics
CA2290893C (en) 1999-11-16 2007-05-01 Bernard Charles Sherman Magnesium omeprazole
DE19959419A1 (en) 1999-12-09 2001-06-21 Ratiopharm Gmbh Stable pharmaceutical preparations comprising a benzimidazole and process for their preparation
AU2583901A (en) * 1999-12-17 2001-06-25 Ariad Pharmaceuticals, Inc. Proton pump inhibitors
US6787342B2 (en) 2000-02-16 2004-09-07 Merial Limited Paste formulations
SE0000773D0 (en) * 2000-03-08 2000-03-08 Astrazeneca Ab New formulation
SE0000774D0 (en) 2000-03-08 2000-03-08 Astrazeneca Ab New formulation
US6306435B1 (en) 2000-06-26 2001-10-23 Yung Shin Pharmaceutical Industrial Co. Ltd. Oral pharmaceutical preparation embedded in an oily matrix and methods of making the same
SE0002476D0 (en) 2000-06-30 2000-06-30 Astrazeneca Ab New compounds
US6544556B1 (en) 2000-09-11 2003-04-08 Andrx Corporation Pharmaceutical formulations containing a non-steroidal antiinflammatory drug and a proton pump inhibitor
AU2001296908A1 (en) * 2000-09-29 2002-04-08 Geneva Pharmaceuticals, Inc. Proton pump inhibitor formulation
WO2002045692A1 (en) 2000-12-07 2002-06-13 Altana Pharma Ag Pharmaceutical preparation in the form of a suspension comprising an acid-labile active ingredient
EP1341528B1 (en) 2000-12-07 2012-01-18 Nycomed GmbH Rapidly disintegrating tablet comprising an acid-labile active ingredient
DK1341524T3 (en) 2000-12-07 2012-01-16 Nycomed Gmbh A pharmaceutical composition in the form of a paste comprising an acid-labile active ingredient
US6645946B1 (en) 2001-03-27 2003-11-11 Pro-Pharmaceuticals, Inc. Delivery of a therapeutic agent in a formulation for reduced toxicity
SE0101379D0 (en) 2001-04-18 2001-04-18 Diabact Ab Composition that inhibits gastric acid secretion
SI20875A (en) 2001-04-25 2002-10-31 LEK, tovarna farmacevtskih in kemi�nih izdelkov, d.d. Crystal form of omeprazole
US8206741B2 (en) 2001-06-01 2012-06-26 Pozen Inc. Pharmaceutical compositions for the coordinated delivery of NSAIDs
CA2449098C (en) * 2001-06-01 2010-01-05 John R. Plachetka Pharmaceutical compositions for the coordinated delivery of nsaids
DE10140492A1 (en) 2001-08-17 2003-08-14 Gruenenthal Gmbh Hydrates of optionally substituted 2- (2-pyridinyl) methylthio-1H-benzimidazoles and process for their preparation
SE0102993D0 (en) 2001-09-07 2001-09-07 Astrazeneca Ab New self emulsifying drug delivery system
US6884810B2 (en) * 2001-09-18 2005-04-26 Zeria Pharmaceutical Co., Ltd. Benzimidazole derivatives
US8101209B2 (en) 2001-10-09 2012-01-24 Flamel Technologies Microparticulate oral galenical form for the delayed and controlled release of pharmaceutical active principles
ES2426723T3 (en) 2001-10-17 2013-10-24 Takeda Pharmaceutical Company Limited Granules containing large amount of chemical compound unstable in acidic medium
US7855082B1 (en) 2001-10-31 2010-12-21 Astrazeneca Ab Raman spectroscopic method for determining the ratio of 5-methoxy and 6-methoxy isomers of omeprazole
US20040006111A1 (en) * 2002-01-25 2004-01-08 Kenneth Widder Transmucosal delivery of proton pump inhibitors
CA2474246C (en) 2002-03-05 2010-06-29 Astrazeneca Ab Alkylammonium salts of omeprazole and esomeprazole
IL164221A0 (en) 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
IL164222A0 (en) 2002-04-09 2005-12-18 Flamel Tech Sa Oral pharmaceutical formulation in the form of aqueous suspension for modified release of active principle(s)
US20030228363A1 (en) * 2002-06-07 2003-12-11 Patel Mahendra R. Stabilized pharmaceutical compositons containing benzimidazole compounds
US20040034078A1 (en) * 2002-06-14 2004-02-19 Agouron Pharmaceuticals, Inc. Benzimidazole inhibitors of poly(ADP-ribosyl) polymerase
KR100822981B1 (en) * 2002-07-19 2008-04-16 윈스턴 파마슈티컬즈, 엘엘씨 Benzimidazole derivatives and their use as prodrugs of proton pump inhibitor
TW200410955A (en) 2002-07-29 2004-07-01 Altana Pharma Ag Novel salt of (S)-PANTOPRAZOLE
EP1534278A4 (en) * 2002-08-01 2006-09-06 Nitromed Inc Nitrosated proton pump inhibitors, compositions and methods of use
MY148805A (en) 2002-10-16 2013-05-31 Takeda Pharmaceutical Controlled release preparation
SE0203065D0 (en) 2002-10-16 2002-10-16 Diabact Ab Gastric acid secretion inhibiting composition
EP2596792A1 (en) 2002-10-16 2013-05-29 Takeda Pharmaceutical Company Limited Stable solid preparations
SE0203092D0 (en) * 2002-10-18 2002-10-18 Astrazeneca Ab Method for the synthesis of a benzimidazole compound
FR2845915B1 (en) 2002-10-21 2006-06-23 Negma Gild USE OF TENATOPRAZOLE FOR THE TREATMENT OF GASTRO-OESOPHAGEAL REFLUX
US20040235903A1 (en) * 2002-10-22 2004-11-25 Khanna Mahavir Singh Amorphous form of esomeprazole salts
DE10254167A1 (en) 2002-11-20 2004-06-09 Icon Genetics Ag Process for the control of cellular processes in plants
CA2507889C (en) 2002-12-06 2012-02-07 Altana Pharma Ag Process for preparing (s)-pantoprazole
MXPA05005762A (en) 2002-12-06 2005-08-16 Altana Pharma Ag Process for preparing optically pure active compounds.
FR2848555B1 (en) 2002-12-16 2006-07-28 Negma Gild ENANTIOMER (-) OF TENATOPRAZOLE AND ITS THERAPEUTIC APPLICATION
EP1572680A2 (en) * 2002-12-19 2005-09-14 Eva Pharmaceutical Industries Ltd. Solid states of pantoprazole sodium, known pantoprazole sodium hydrates, processes for their preparation.
US20040166162A1 (en) * 2003-01-24 2004-08-26 Robert Niecestro Novel pharmaceutical formulation containing a proton pump inhibitor and an antacid
JP2006518751A (en) * 2003-02-20 2006-08-17 サンタラス インコーポレイティッド Novel formulation for rapid and sustained suppression of gastric acid, omeprazole antacid complex-immediate release
US20040185119A1 (en) * 2003-02-26 2004-09-23 Theuer Richard C. Method and compositions for treating gastric hyperacidity while diminishing the likelihood of producing vitamin deficiency
CA2518999A1 (en) * 2003-03-12 2004-09-23 Teva Pharmaceutical Industries Ltd Crystalline and amorphous solids of pantoprazole and processes for their preparation
US7608625B2 (en) * 2003-03-13 2009-10-27 Eisai R & D Management Co., Ltd. Method for treating bruxism and bruxism-related diseases
US20040185092A1 (en) * 2003-03-18 2004-09-23 Yih Ming Hsiao Pharmaceutical preparations of omeprazole and/or clarithromycin for oral use
JP2006523201A (en) * 2003-03-28 2006-10-12 シデム ファーマ Process for the enantioselective preparation of sulfoxide derivatives
FR2852956B1 (en) * 2003-03-28 2006-08-04 Negma Gild PROCESS FOR THE ENANTIOSELECTIVE PREPARATION OF SULFOXIDE DERIVATIVES
CL2004000983A1 (en) 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 (en) 2003-05-08 2005-03-22 Altana Pharma Ag A DOSAGE FORM CONTAINING (S) -PANTOPRAZOLE AS AN ACTIVE INGREDIENT
US7524837B2 (en) * 2003-05-12 2009-04-28 Janssen Pharmaceutica N.V. Benzotriazapinone salts and methods for using same
EP1615913A2 (en) * 2003-06-10 2006-01-18 Teva Pharmaceutical Industries Limited Process for preparing 2-(pyridinyl)methyl sulfinyl-substituted benzimidazoles and novel chlorinated derivatives of pantoprazole
CA2529984C (en) * 2003-06-26 2012-09-25 Isa Odidi Oral multi-functional pharmaceutical capsule preparations of proton pump inhibitors
CN1823058A (en) * 2003-07-15 2006-08-23 阿勒根公司 Process for preparing isomerically pure prodrugs of proton pump inhibitors
MXPA06000524A (en) * 2003-07-18 2006-08-11 Santarus Inc Pharmaceutical formulation and method for treating acid-caused gastrointestinal disorders.
US8993599B2 (en) 2003-07-18 2015-03-31 Santarus, Inc. Pharmaceutical formulations useful for inhibiting acid secretion and methods for making and using them
MXPA06000529A (en) * 2003-07-18 2006-08-11 Santarus Inc Pharmaceutical composition for inhibiting acid secretion.
WO2005020954A2 (en) * 2003-09-03 2005-03-10 Agi Therapeutics Limited Proton pump inhibitor formulations, and methods of preparing and using such formulations
SE0302382D0 (en) 2003-09-04 2003-09-04 Astrazeneca Ab New salts II
SE0302381D0 (en) 2003-09-04 2003-09-04 Astrazeneca Ab New salts I
TWI372066B (en) 2003-10-01 2012-09-11 Wyeth Corp Pantoprazole multiparticulate formulations
US20060241037A1 (en) * 2003-10-03 2006-10-26 Allergan Inc. Compositions comprising trefoil factor family peptides and/or mucoadhesives and proton pump ihhibitor prodrugs
US20050075371A1 (en) * 2003-10-03 2005-04-07 Allergan, Inc. Methods and compositions for the oral administration of prodrugs of proton pump inhibitors
US20070202119A1 (en) * 2003-10-24 2007-08-30 Ashdown Martin L Method Of Therapy
US20070292498A1 (en) * 2003-11-05 2007-12-20 Warren Hall Combinations of proton pump inhibitors, sleep aids, buffers and pain relievers
EP1716136A1 (en) 2004-02-11 2006-11-02 Ulkar Kimya Sanayii Ve Ticaret A.S. Pyridine benzimidazole sulfoxides of high purity
US20070161679A1 (en) * 2004-02-18 2007-07-12 Allergan, Inc. Method and compositions for the intravenous administration of compounds related to proton pump inhibitors
JP2007523163A (en) * 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
SE0400410D0 (en) 2004-02-20 2004-02-20 Astrazeneca Ab New compounds
WO2005097083A2 (en) * 2004-03-30 2005-10-20 Dermatrends,Inc. Transdermal administration of proton pump inhibitors
US7176319B2 (en) 2004-04-28 2007-02-13 Hetero Drugs Limited Process for substituted sulfoxides
US8906940B2 (en) 2004-05-25 2014-12-09 Santarus, Inc. Pharmaceutical formulations useful for inhibiting acid secretion and methods for making and using them
US8815916B2 (en) 2004-05-25 2014-08-26 Santarus, Inc. Pharmaceutical formulations useful for inhibiting acid secretion and methods for making and using them
US7365206B2 (en) 2004-05-28 2008-04-29 Hetero Drugs Limited Stereoselective synthesis of benzimidazole sulfoxides
US20050267157A1 (en) * 2004-05-28 2005-12-01 David White Magnesium-S-omeprazole
BRPI0511515A (en) * 2004-06-02 2007-12-26 Altana Pharma Ag process for the preparation of pyridin-2-ylmethylsulfinyl-1h-benzimidazole compounds
US8394409B2 (en) 2004-07-01 2013-03-12 Intellipharmaceutics Corp. Controlled extended drug release technology
US20060024362A1 (en) * 2004-07-29 2006-02-02 Pawan Seth Composition comprising a benzimidazole and process for its manufacture
US10624858B2 (en) 2004-08-23 2020-04-21 Intellipharmaceutics Corp Controlled release composition using transition coating, and method of preparing same
KR101276915B1 (en) 2004-09-13 2013-06-19 다케다 야쿠힌 고교 가부시키가이샤 Method and apparatus for producing oxidized compound
US8541026B2 (en) 2004-09-24 2013-09-24 Abbvie Inc. Sustained release formulations of opioid and nonopioid analgesics
EP2417986A1 (en) 2004-11-22 2012-02-15 Anadis Ltd. Bioactive compositions
CN101111233A (en) 2004-12-23 2008-01-23 兰贝克赛实验室有限公司 Stable oral benzimidazole compositions and process of preparation thereof
EP1845982A2 (en) * 2005-02-02 2007-10-24 Ranbaxy Laboratories Limited Stable oral benzimidazole compositions prepared by non-aqueous layering process
EP1852100B1 (en) 2005-02-25 2018-05-09 Takeda Pharmaceutical Company Limited Method for producing coated granules of a benzimidazole compound
US7981908B2 (en) 2005-05-11 2011-07-19 Vecta, Ltd. Compositions and methods for inhibiting gastric acid secretion
US7803817B2 (en) 2005-05-11 2010-09-28 Vecta, Ltd. Composition and methods for inhibiting gastric acid secretion
US7563812B2 (en) 2005-06-15 2009-07-21 Hetero Drugs Limited Amorphous esomeprazole hydrate
US20080200533A1 (en) * 2005-07-04 2008-08-21 Ramu Krishnan Drug or Pharmaceutical Compounds and a Preparation Thereof
EP1904064A4 (en) * 2005-07-07 2009-12-02 Reddys Lab Ltd Dr Omeprazole form b
CA2615678C (en) * 2005-07-26 2015-01-20 Nycomed Gmbh Isotopically substituted pantoprazole
US7601737B2 (en) * 2005-07-26 2009-10-13 Nycomed Gmbh Isotopically substituted proton pump inhibitors
NZ565078A (en) * 2005-07-26 2010-03-26 Nycomed Gmbh Deuterated proton pump inhibitors such as omeprazole
EP1934201A1 (en) * 2005-10-06 2008-06-25 Auspex Pharmaceuticals Inc. Deuterated inhibitors of gastric h+, k+-atpase with enhanced therapeutic properties
US7576219B2 (en) 2005-10-26 2009-08-18 Hanmi Pharm. Co., Ltd Crystalline S-omeprazole strontium hydrate, method for preparing same, and pharmaceutical composition containing same
US8124779B2 (en) 2005-12-05 2012-02-28 Astrazeneca Ab Process for the preparation of esomeprazole non-salt form
EP1801110A1 (en) 2005-12-22 2007-06-27 KRKA, tovarna zdravil, d.d., Novo mesto Esomeprazole arginine salt
US10064828B1 (en) 2005-12-23 2018-09-04 Intellipharmaceutics Corp. Pulsed extended-pulsed and extended-pulsed pulsed drug delivery systems
CA2634232C (en) 2005-12-28 2013-08-20 Takeda Pharmaceutical Company Limited Method of producing solid preparation disintegrating in the oral cavity
DE602006006352D1 (en) 2005-12-28 2009-05-28 Union Quimico Farma PROCESS FOR PREPARING THE (S) -ENANTIOMER OF OMEPRAZOLE
US9561188B2 (en) * 2006-04-03 2017-02-07 Intellipharmaceutics Corporation Controlled release delivery device comprising an organosol coat
US10960077B2 (en) 2006-05-12 2021-03-30 Intellipharmaceutics Corp. Abuse and alcohol resistant drug composition
US7786309B2 (en) 2006-06-09 2010-08-31 Apotex Pharmachem Inc. Process for the preparation of esomeprazole and salts thereof
US7863330B2 (en) * 2006-06-14 2011-01-04 Rottapharm S.P.A. Deloxiglumide and proton pump inhibitor combination in the treatment of gastrointestinal disorders
RU2467747C2 (en) 2006-07-25 2012-11-27 Векта Лтд. Compositions and methods for gastric acid secretion inhibition with using small dicarboxylic acid derivatives in combination with ppi
WO2008036201A1 (en) * 2006-09-19 2008-03-27 Alevium Pharmaceuticals, Inc. Prodrugs of proton pump inhibitors including the 1h-imidazo[4,5-b] pyridine moiety
CA2665226C (en) 2006-10-05 2014-05-13 Santarus, Inc. Novel formulations of proton pump inhibitors and methods of using these formulations
US20090092658A1 (en) * 2007-10-05 2009-04-09 Santarus, Inc. Novel formulations of proton pump inhibitors and methods of using these formulations
WO2008057802A2 (en) 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
HUE046465T2 (en) 2006-12-22 2020-03-30 Ironwood Pharmaceuticals Inc Compositions comprising bile acid sequestrants for treating esophageal disorders
EP1947099A1 (en) 2007-01-18 2008-07-23 LEK Pharmaceuticals D.D. Process for solvent removal from omeprazole salts
EP2114919A2 (en) 2007-01-31 2009-11-11 Krka Tovarna Zdravil, D.D., Novo Mesto Process for the preparation of optically pure omeprazole via salt formation with a chiral amine or treatment with an entiomer converting enzyme and chromatographic seperation
US20080194307A1 (en) * 2007-02-13 2008-08-14 Jeff Sanger Sports-based game of chance
WO2008102145A2 (en) * 2007-02-21 2008-08-28 Cipla Limited Process for the preparation of esomeprazole magnesium dihydrate
EP2118052A4 (en) * 2007-03-15 2010-04-14 Sun Pharma Advanced Res Co Ltd Novel prodrugs
ATE534643T1 (en) * 2007-06-07 2011-12-15 Aurobindo Pharma Ltd IMPROVED METHOD FOR PRODUCING AN OPTICALLY ACTIVE PROTON PUMP INHIBITOR
US20100210847A1 (en) * 2007-07-17 2010-08-19 Ranbaxy Laboratories Limited Process for the preparation of pantoprazole sodium and pantoprazole sodium sesquihydrate
WO2009066317A2 (en) * 2007-08-20 2009-05-28 Macleods Pharmaceuticals Limited Process for the preparation of pantoprazole sodium
US8106210B2 (en) 2007-10-08 2012-01-31 Hetero Drugs Limited Polymorphs of esomeprazole salts
CN101450939B (en) * 2007-12-05 2013-06-19 沈阳药科大学 Novel benzimidazoles compounds
CA2716367C (en) 2008-02-20 2015-05-26 The Curators Of The University Of Missouri Composition comprising a combination of omeprazole and lansoprazole, and a buffering agent, and methods of using same
US8911787B2 (en) 2008-02-26 2014-12-16 Ranbaxy Laboratories Limited Stable oral benzimidazole compositions and process of preparation thereof
AR072858A1 (en) * 2008-04-15 2010-09-29 Schering Corp HIGH DENSITY COMPOSITIONS CONTAINING POSACONAZOL AND FORMULATIONS THAT INCLUDE IT
AU2009236290A1 (en) * 2008-04-15 2009-10-22 Merck Sharp & Dohme Corp. Oral pharmaceutical compositions in a solid dispersion comprising preferably posaconazole and HPMCAS
KR101044880B1 (en) * 2008-06-12 2011-06-28 일양약품주식회사 Process for Preparing Intermediate Compound for Synthesizing an Antiulcerant
EP2147918A1 (en) 2008-07-21 2010-01-27 LEK Pharmaceuticals D.D. Process for the preparation of S-omeprazole magnesium in a stable form
CH699302B1 (en) * 2008-08-11 2012-03-15 Mepha Gmbh An oral pharmaceutical formulation for omeprazole containing a specific release layer.
EA201100313A1 (en) 2008-09-09 2011-10-31 Астразенека Аб METHOD OF DELIVERY OF THE PHARMACEUTICAL COMPOSITION TO THE PATIENT NEEDING THIS
CA2740095A1 (en) * 2008-10-10 2010-04-15 Celtaxsys, Inc. Method of inducing negative chemotaxis
EP2264024A1 (en) 2008-10-14 2010-12-22 LEK Pharmaceuticals d.d. Process for the preparation of enantiomerically enriched proton pump inhibitors
EP2435825B8 (en) 2009-05-27 2015-09-02 Biotempus Limited Methods of treating diseases
AU2010263304A1 (en) 2009-06-25 2012-02-02 Astrazeneca Ab Method for treating a patient at risk for developing an NSAID-associated ulcer
WO2010151697A1 (en) * 2009-06-25 2010-12-29 Pozen Inc. Method for treating a patient in need of aspirin therapy
WO2011058569A1 (en) 2009-11-12 2011-05-19 Hetero Research Foundation Process for the resolution of omeprazole
WO2011080502A2 (en) 2009-12-29 2011-07-07 Orexo Ab New pharmaceutical dosage form for the treatment of gastric acid-related disorders
EP2519229A2 (en) 2009-12-29 2012-11-07 Novartis AG New pharmaceutical dosage form for the treatment of gastric acid-related disorders
WO2011080500A2 (en) 2009-12-29 2011-07-07 Orexo Ab New pharmaceutical dosage form for the treatment of gastric acid-related disorders
EP2345408A3 (en) 2010-01-08 2012-02-29 Dr. Reddy's Laboratories Ltd. Acid labile drug formulations
CN102140099A (en) 2010-02-02 2011-08-03 山东轩竹医药科技有限公司 Novel pyridine derivative
US9623622B2 (en) * 2010-02-24 2017-04-18 Michael Baines Packaging materials and methods
US20130156720A1 (en) 2010-08-27 2013-06-20 Ironwood Pharmaceuticals, Inc. Compositions and methods for treating or preventing metabolic syndrome and related diseases and disorders
US9233103B2 (en) 2011-03-25 2016-01-12 Takeda Pharmaceuticals U.S.A., Inc. Methods for treating heartburn, gastric bleeding or hemorrhage in patients receiving clopidogrel therapy
US20140343104A1 (en) 2011-08-26 2014-11-20 National University Corporation Nagoya University Osteogenesis promoter and use thereof
US20130065874A1 (en) 2011-09-09 2013-03-14 Cubist Pharmaceuticals, Inc. Methods for treating intrapulmonary infections
WO2013081566A1 (en) 2011-11-25 2013-06-06 Mahmut Bilgic A formulation comprising benzimidazole
EP2601947A1 (en) 2011-12-05 2013-06-12 Abo Bakr Mohammed Ali Al-Mehdar Fixed-dose combination for treatment of helicobacter pylori associated diseases
WO2013101897A2 (en) 2011-12-28 2013-07-04 Pozen Inc. Improved compositions and methods for delivery of omeprazole plus acetylsalicylic acid
CN102584792B (en) * 2012-01-06 2014-06-11 南京优科生物医药研究有限公司 Method for preparing high-purity esomeprazole
US8809314B1 (en) 2012-09-07 2014-08-19 Cubist Pharmacueticals, Inc. Cephalosporin compound
US8476425B1 (en) 2012-09-27 2013-07-02 Cubist Pharmaceuticals, Inc. Tazobactam arginine compositions
JP6716255B2 (en) 2013-01-15 2020-07-01 アイロンウッド ファーマシューティカルズ，インコーポレーテッドＩｒｏｎｗｏｏｄ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． Gastroretentive sustained release oral dosage form of bile acid scavenger
US20140275000A1 (en) 2013-03-15 2014-09-18 Cubist Pharmaceuticals, Inc. Ceftolozane pharmaceutical compositions
AU2014227660B2 (en) 2013-03-15 2014-11-06 Merck Sharp & Dohme Llc Ceftolozane antibiotic compositions
US9872906B2 (en) 2013-03-15 2018-01-23 Merck Sharp & Dohme Corp. Ceftolozane antibiotic compositions
GB201306720D0 (en) 2013-04-12 2013-05-29 Special Products Ltd Formulation
ES2800603T3 (en) 2013-09-09 2021-01-04 Merck Sharp & Dohme Treatment of infections with ceftolozane / tazobactam in patients with renal impairment
US20150094293A1 (en) 2013-09-27 2015-04-02 Calixa Therapeutics, Inc. Solid forms of ceftolozane
US9457011B2 (en) 2014-02-25 2016-10-04 Muslim D. Shahid Compositions and methods for the treatment of acid-related gastrointestinal disorders containing a dithiolane compound and a gastric acid secretion inhibitor
FR3018812A1 (en) 2014-03-21 2015-09-25 Minakem NOVEL INTERMEDIATE PHASE OF FORM A OF MAGNESIUM SALT DIHYDRATE OF AN OMEPRAZOLE ENANTIOMER
EP2929885A1 (en) 2014-04-11 2015-10-14 Sanovel Ilac Sanayi ve Ticaret A.S. Pharmaceutical combinations of rivaroxaban and proton pump inhibitors
US10130618B2 (en) 2014-04-11 2018-11-20 Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi Pharmaceutical combinations of dabigatran and proton pump inhibitors
CN104045627A (en) * 2014-05-21 2014-09-17 丽珠医药集团股份有限公司 Purification method of omeprazole
CA2952069C (en) 2014-06-16 2022-06-14 University Of Rochester Small molecule anti-scarring agents
WO2016126625A1 (en) 2015-02-03 2016-08-11 Ironwood Pharmaceuticals, Inc. Methods of treating upper gastrointestinal disorders in ppi refractory gerd
US20170042806A1 (en) 2015-04-29 2017-02-16 Dexcel Pharma Technologies Ltd. Orally disintegrating compositions
US10736855B2 (en) 2016-02-25 2020-08-11 Dexcel Pharma Technologies Ltd. Compositions comprising proton pump inhibitors
US10076494B2 (en) 2016-06-16 2018-09-18 Dexcel Pharma Technologies Ltd. Stable orally disintegrating pharmaceutical compositions
AU2017310506B2 (en) * 2016-08-11 2019-11-21 Dmk Pharmaceuticals Corporation Drug compositions
EP3292862A1 (en) 2016-09-07 2018-03-14 Sandoz Ag Omeprazole formulations
EP3720844A4 (en) 2017-12-08 2021-08-11 Adamis Pharmaceuticals Corporation Drug compositions
CN110317164B (en) * 2019-07-06 2022-08-19 抚州三和医药化工有限公司 Preparation method of omeprazole intermediate
US20220257597A1 (en) 2021-01-29 2022-08-18 Abbvie Inc. Methods of Administering Elagolix

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1234058A (en) * 1968-10-21 1971-06-03
US4045564A (en) * 1974-02-18 1977-08-30 Ab Hassle Benzimidazole derivatives useful as gastric acid secretion inhibitors
SE418966B (en) * 1974-02-18 1981-07-06 Haessle Ab ANALOGY PROCEDURE FOR THE PREPARATION OF COMPOUNDS WITH Gastric Acid Secretion Inhibitory Effects
SE416649B (en) * 1974-05-16 1981-01-26 Haessle Ab PROCEDURE FOR THE PREPARATION OF SUBSTANCES WHICH PREVENT Gastric acid secretion
IN148930B (en) * 1977-09-19 1981-07-25 Hoffmann La Roche

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995012590A1 (en) 1993-11-04 1995-05-11 Torcan Chemical Ltd. Preparation of omeprazole and lansoprazole and intermediates useful therein
US6121454A (en) * 1997-05-06 2000-09-19 Pdi-Research Laboratories, Inc. Synthesis of pharmaceutically useful pyridine derivatives
US6437139B1 (en) 1997-05-06 2002-08-20 Pdi-Research Laboratories, Inc. Synthesis of pharmaceutically useful pyridine derivatives
US6077541A (en) * 1997-11-14 2000-06-20 Andrx Pharmaceuticals, Inc. Omeprazole formulation
US6096340A (en) * 1997-11-14 2000-08-01 Andrx Pharmaceuticals, Inc. Omeprazole formulation
US6780435B2 (en) 1997-11-14 2004-08-24 Andrx Pharmaceuticals, Inc. Omeprazole formulation
US6855336B2 (en) 1998-08-28 2005-02-15 Andrx Pharmaceuticals, Inc. Omeprazole formulation
US6174548B1 (en) 1998-08-28 2001-01-16 Andrx Pharmaceuticals, Inc. Omeprazole formulation
US6733778B1 (en) 1999-08-27 2004-05-11 Andrx Pharmaceuticals, Inc. Omeprazole formulation
US7129358B2 (en) 2001-02-02 2006-10-31 Teva Pharmaceutical Industries Ltd. Processes for the production of substituted 2-(2-pyridylmethyl) sulfinyl-1H-benzimidazoles
EP1970374A1 (en) 2001-02-02 2008-09-17 Teva Pharmaceutical Industries Ltd. Process for the production of substituted 2-(pyridin-2-ylmethylsulfinyl)-1H-benzimidazoles
WO2010134099A1 (en) 2009-05-21 2010-11-25 Cadila Healthcare Limited One pot process for preparing omeprazole and related compounds
WO2013108068A1 (en) 2012-01-21 2013-07-25 Jubilant Life Sciences Limited Process for the preparation of 2-pyridinylmethylsulfinyl benzimidazoles, their analogs and optically active enantiomers

Also Published As

Publication number Publication date
NO1994027I1 (en) 1994-12-21
AT374471B (en) 1984-04-25
HU179022B (en) 1982-08-28
LU88305I2 (en) 1994-05-04
NL930075I2 (en) 1994-02-16
JPS58192880A (en) 1983-11-10
ATA290483A (en) 1989-08-15
JPS6034956B2 (en) 1985-08-12
NO152785B (en) 1985-08-12
NL930074I2 (en) 1994-02-16
NO152216C (en) 1985-08-21
AU529654B2 (en) 1983-06-16
CS261851B2 (en) 1989-02-10
IE790785L (en) 1979-10-14
SG63383G (en) 1984-07-27
DK150510C (en) 1987-12-07
FI65067B (en) 1983-11-30
DE2960293D1 (en) 1981-08-06
JPS54141783A (en) 1979-11-05
MY8500074A (en) 1985-12-31
EP0005129A1 (en) 1979-10-31
NL930075I1 (en) 1993-09-16
LU88307I2 (en) 1994-05-04
NZ190203A (en) 1984-03-16
SU878196A3 (en) 1981-10-30
IE48370B1 (en) 1984-12-26
EP0005129B1 (en) 1981-04-29
BG61492B2 (en) 1997-09-30
US4508905A (en) 1985-04-02
FI65067C (en) 1984-03-12
NO1995006I1 (en) 1995-06-14
DK151179A (en) 1979-10-15
DK150510B (en) 1987-03-16
CY1232A (en) 1984-06-29
NO791227L (en) 1979-10-16
US4255431A (en) 1981-03-10
US4337257A (en) 1982-06-29
SU873880A3 (en) 1981-10-15
NO1995005I1 (en) 1995-06-14
SU895292A3 (en) 1981-12-30
AT389995B (en) 1990-02-26
NO152785C (en) 1985-11-20
AU4602779A (en) 1979-10-18
LT2274B (en) 1993-12-15
FI791219A (en) 1979-10-15
ZA791586B (en) 1980-04-30
NO152216B (en) 1985-05-13
JPS6353191B2 (en) 1988-10-21
SU873879A3 (en) 1981-10-15
DD142882A5 (en) 1980-07-16
NL930074I1 (en) 1993-09-16
HK15284A (en) 1984-03-02
NO840112L (en) 1979-10-16
CS254979A2 (en) 1988-07-15
ATA273279A (en) 1983-09-15
SE7804231L (en) 1979-10-15

Similar Documents

Publication Publication Date Title
CA1127158A (en) 2-pyridylmethylsulfinyl-benzimidazole compounds
CA1055033A (en) 2-(2-heterocyclic-methylsulphinyl)-benzimidazole compounds
US4359465A (en) Methods for treating gastrointestinal inflammation
US4045564A (en) Benzimidazole derivatives useful as gastric acid secretion inhibitors
US5039808A (en) Therapeutically active cyclopropyl substituted compound
CA1060448A (en) Gastric acid secretion agents
EP0654471B1 (en) Pyridine derivatives, pharmaceutical compositions comprising the same, the use of the same for the manufacture of medicaments having therapeutic or preventative value, and process for preparing the same
CA1226223A (en) Pharmaceutical compositions containing benzimidazole compounds
HU187521B (en) Process for producing new substituted benzimidazoles
IL129724A (en) Production of crystals of benzimidazole derivatives
AU639429B2 (en) Compound with gastric acid inhibitory effect and process for its preparation
CA1129417A (en) Gastric acid secretion inhibiting substituted 2-(2- benzimidazolyl)-pyridines, their preparation, pharmaceutical preparations containing same, and method for inhibiting gastricacid secretion
EP0354788B1 (en) Novel imidazole derivatives
US5049674A (en) Therapeutically active fluoro substituted benzimidazoles
NZ198426A (en) 2-(di- or tri-methylpyrid-2-ylmethylsulphinyl) benzimidazoles
CS261874B2 (en) Process for preparing 2-pyridylmethylsulphinylbenzimidazoles
BE834973A (en) AGENTS AFFECTING GASTRIC ACID SECRETION
JPH01207277A (en) Quaternary salt of benzimidazole derivative

Legal Events

Date Code Title Description
MKEX Expiry