GB2069492A - Novel sulphur compounds - Google Patents
Novel sulphur compounds Download PDFInfo
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- GB2069492A GB2069492A GB8104411A GB8104411A GB2069492A GB 2069492 A GB2069492 A GB 2069492A GB 8104411 A GB8104411 A GB 8104411A GB 8104411 A GB8104411 A GB 8104411A GB 2069492 A GB2069492 A GB 2069492A
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- compound
- acid addition
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/32—Sulfur atoms
- C07D213/34—Sulfur atoms to which a second hetero atom is attached
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Abstract
The invention relates to sulphoxide compounds of formula I <IMAGE> wherein R represents hydrogen, lower alkyl, aryl or aralkyl, R<1> represents hydrogen or fluorine, R<2> represents hydrogen, fluorine, chlorine, or trifluoromethyl, n is 1 or 2, and pharmaceutically acceptable acid addition salts thereof. The preparation of the sulphoxides by oxidation of corresponding thioethers is also covered as well as some of the thioethers themselves which are novel. The use of the sulphoxides in the treatment of ulcers and hypersecretion is disclosed together with pharmaceutical compositions.
Description
SPECIFICATION
Novel sulphur compounds
The invention relates to novel sulphur compounds which have activity in tests for anti-ulcer and/or anti-secretory activity.
The invention provides compounds of formula
wherein R represents hydrogen, lower alkyl, aryl or aralkyl, R1 represents hydrogen or fluorine, R2 represents hydrogen, fluorine, chlorine, or trifluoromethyl, n is 1 or 2, and pharmaceutically acceptable acid addition salts thereof.
Preferably not more than two R2 groups are chlorine or trifluoromethyl.
In this specification lower alkyl group has from 1 to 6 carbon atoms eg methyl, ethyl, n-propyl, isopropyl, n-butyl, s-butyl, t-butyl, n-pentyl and n-hexyl. A loweralkoxy substituent is alkoxy in which the alkyl portion is as defined for a lower alkyl group. Whenever the term lower alkyl is used as part of another radical, eg arylloweralkyl, the lower alkyl or lower alkoxy portion has 1 to 6 carbon atoms unless otherwise stated.
The aryl group R is preferably phenyl or substituted phenyl, substituents being halogen, lower alkyl, lower alkoxy and so on.
The acid addition salts of compounds of formula I may be of an organic or inorganic acid, eg hydrochloric, hydrobromic, phosphoric, sulphuric, nitric, citric, acetic, formic, fumaric, maleic tartaric, embonic, methane sulphonic and p-toluene sulphonic acids.
The compounds of formula I and their acid addition salts may be used in pharmaceutical compositions.
For the pharmaceutical compositions any suitable carrier known in the art can be used. In such a composition, the carrier may be a solid, liquid, or mixture of a solid and a liquid. Solid form compositions include powders, tablets and capsules. A solid carrier can be one or more substances which may also act as flavouring agents, lubricants, solubilisers, suspending agents, binders, or tablet disintegrating agents; it can also be encapsulating material. In powders the carrier is a finely divided solid which is in admixture with the finely divided active ingredient. In tablets the active ingredient is mixed with a carrier having the necessary binding properties in suitable proportions and compacted in the shape and size desired. The powders and tablets preferably contain from 5 to 99, preferably 1080% of the active ingredient.Suitable solid carriers are magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, starch, gelatin, tragacanth, methyl cellulose, sodium carboxymethyl cellulose, a low melting wax and cocoa butter. The term "composition" is intended to include the formulation of an active ingredient with encapsulating material as carrier, to give a capsule in which the active ingredient (with or without other carriers) is surrounded by carriers, which is thus in association with it. Similarly cachets are included.
Sterile liquid form compositions include sterile solutions, suspensions, emulsions, syrups and elixirs. The active ingredient can be dissolved or suspended in a pharmaceutically acceptable carrier, such as sterile water, sterile organic solvent or a mixture of both. The active ingredient can often be dissolved in a suitable organic solvent, for instance aqueous propylene glycol containing from 10 to 75% of the glycol by weight is generally suitable. In other instances compositions can be made by dispersing the finely-divided active ingredient in aqueous starch or sodium carboxymethyl cellulose solution, or in a suitable oil, for instance arachis oil.
Preferably the pharmaceutical composition is in unit dosage form, the composition is sub-divided in unit doses containing appropriate quantities of the active ingredient; the unit dosage form can be a packaged composition, the package containing specific quantities of compositions, for example packeted powders or vials or ampoules. The unit dosage form can be a capsule, cachet or tablet itself, or it can be the appropriate number of any of these in packaged form. The quantity of active ingredient in a unit dose of composition may be varied or adjusted from 10 to 500 mg or more, eg 25 mg to 250 mg, according to the particular need and the activity of the active ingredient. The invention also includes the compounds in the absence of carrier where the compounds are in unit dosage form.
The anti-ulcer compositions of the invention will be administered orally in either liquid or solid composition form. These compositions may include one or more antacid ingredients, eg aluminium hydroxide, magnesium hydroxide or bismuth carbonate, aluminium glycinate, calcium carbonate, magnesium trisilicate, sodium bicarbonate or the alumina gel described in British Specification No 1,284,394.
Anti-ulcer activity was determined by the stress-induced erosion test of Senay s Levine, Proc Soc
Exp Biol Med, 124, 1221-3(1967) and anti-secretory activity by the test of H Shay, D Sun and H
Gruenstein, Gastroenterology, 1954,26,903-13 as exemplified by Beattie et al J Med Chem 20,714 (1977). Compounds which possess one or both these activities are considered to be anti-ulcer agents which can be used for the treatment of ulcers or hypersecretion in mammals. The compounds of formula I which we have tested possess one or both of the above activities.
In another aspect the invention provides as an anti-ulcer agent a compound of formula I or an acid addition salt thereof as defined above.
The invention also includes a method for preparing a compound of formula I, or an acid addition salt thereof, which method comprises oxidising a corresponding compound of formula II
or an acid addition salt thereof wherein R, R', R2 and n are as defined in connection with formula I, and if desired converting the product to an acid addition salt.
Oxidation may be effected by any suitable means for forming a sulphoxide from a thioether (see
Kharasch, Organic Sulphur Compounds, Pergamon Press, New York, 1961,Volume 1, pages 157-159), for example by a per acid or peroxide. Examples of per acids are perbenzoic, mchloroperbenzoic or peracetic acid. Hydrogen peroxide may also be used. Preferably an addition salt of compound Il is used in order to prevent or minimise attack of the pyridine nitrogen by the oxidising agent.
The starting materials of formula II are either known compounds or may be prepared by standard methods, eg reaction of a thiol compound of formula Ill, or alkali metal salt thereof
where R1 and R2 are as defined above with a pyridine derivative of formula IV
wherein n is 1 or 2 and Hal is a halogen atom, especially chlorine, bromine or iodine and R is as defined above.
The invention includes a method of treating ulcers or hypersecretion in a mammal, which method comprises administering to said mammal an effective amount of a compound of formula I or an acid addition salt thereof. The amount of compound used will depend on the activity of the compound and the needs of the mammal being treated. Doses may range from 1 to 100 mg/kg.
The invention is illustrated by the following Examples:
EXAMPLE 1 2-(KPhenylsulphinylmethylJpyridine) A) Thiophenol (21 ml) was added to a solution of sodium (4.6 g) in ethanol (100 ml). To the resulting solution use was added 2-picolyl chloride, hydrochloride (15 g) and the mixture was heated at reflux for 2 hours. Precipitated sodium chloride was removed by filtration and the solution was acidified with ethereal HCI. The solvent was removed by evaporation and the residue induced to crystallise by trituration with ether. Recrystallisation from ethanol-ether gave 2-((phenylthio) methyl)pyridine, hydrochloride (5.0 g) mp 142--40C (Found: C,60.6; H,5.25; N,5.5 C,2H"NS,HCI requires C,60.6; H,5.1;
N,5.9%).
B) A solution of 2-((phenylthio)methylpyridine, hydrochloride (1g) in chloroform (10 ml) was cooled to 50C and treated with m-chloroperoxybenzoic acid (1 g) and the mixture was stirred for 2 hour.
The solution was washed with saturated Na2CO3 solution dried (MgSO4) and evaporated. The residue was converted into the hydrochloride in ether with ethereal HCI and this was triturated with ether and with acetone to give a solid which was removed by filtration and dried to give the title compound as the hydrochloride (0.8 g) mp 140-1 0C decomp (Found: C, 55.8; H, 4.9; N, 5.4 C,2H"NOS, HCl-41H2O requires C, 55.65; H, 4.7; N, 5.5%).
EXAMPLE 2 2-(((4-Chlorophenyl)sulphinyl)methyl)pyrid!ne A) 4-Chlorobenzenethiol (5 g) in warm ethanol (5 ml) was added to a solution of sodium hydroxide (2.8 g) in ethanol (50 ml). To the solution was added a solution of 2-picolyl chloride, hydrochloride (5.7 g) in ethanol (25 ml) and the mixture was stirred at ambient temperature for 6 hours. The mixture was filtered and evaporated and the residue was converted into the hydrochloride with ethereal HCI solution and this was recrystallised from ethanol-ether to give 2-(((4-chlorophenyl)thio)methyl)pyridine, hydrochloride (8 g) mp 1 96-80C (Found: C, 52.95; H, 4.1; N, 5.15 C12H10ClNS.HCl requires C, 53.1; H, 4.2; N,4.9%).
B) A suspension of 2-(((4-chlorophenyl)thio)methyl) pyridine, hydrochloride (2.0 g) in methylene chloride (50 ml) at OOC was treated with a solution of m-chloroperoxybenzoic acid (1.7 g) in CH2CI2 (25 ml). The mixture was allowed to warm to ambient temperature and was stirred for 5 hours. The solution was washed with saturated sodium carbonate solution and water, then dried (MgSO4). The residue was dissolved in acetone and converted into the hydrochloride with ethereal HCI. N.m.r. showed approximately 20% of starting material remaining so the material was suspended in methylene chloride (50 ml) and treated with further m-chloroperoxybenzoic acid (2 x 500 g).The solution was washed with saturated sodium carbonate solution and water, dried (MgSO4) evaporated and the residue was dissolved in acetone and the hydrochloride precipitated with ethereal HCI solution. Recrystallisation from acetone-ether gave the title compound as the hydrochloride (0.7 g) mp 1 700C decomp. (Found: C, 49.2; H, 3.8; N, 4.5 C12HloCINOS.HCl.H20 requires C,49.2; H, 4.0; N,4.8%).
EXAMPLE 3 2 -(((3,4-Dichlorophen y!)sulphin yI)me thyl)pyridine A) 3,4-Dichlorobenzenethiol (5 g) was added to a solution of sodium hydroxide 2.25 g) in ethanol (50 ml) and the resulting solution was treated with 2-picolyl chloride, hydrochloride (4.6 g) in ethanol (25 ml). After stirring for 4 hours at ambient temperature the mixture was filtered and the solvent removed by evaporation. The residue was converted into the hydrochloride with ethereal HCI and this was recrystallised from ethanol/ether to give 2-(((3,4-dichlorophenyl)thio)methyl)pyridine, hydrochloride (5.5 g) mp 213--40C (Found: C, 46.7; H, 3.3; N, 4.4 C12H9Cl2NS.HCl requires C,47.0; H,3.3; N, 4.6%).
B) A suspension of 2-(((3,4-dichlorophenyl)thio)methyl)pyridine, hydrochloride (2.0 g) in methylene chloride (50 ml) at OOC was treated with a solution of m-chloroperoxybenzoic acid (1.5 g) in methylene chloride (25 ml). The mixture was allowed to warm to ambient temperature and was stirred for 5 hours. The solution was washed with saturated sodium carbonate solution and water, then dried (MgS04). The residue was dissolved in acetone and converted into the hydrochloride with ethereal HCI.
N.m.r. showed approximately 35% of starting material remaining so the material was suspended in methylene chloride (50 ml) and treated with further m-chloroperoxybenzoic acid (2 x 500 g). The solution was washed with saturated sodium carbonate solution and water, dried (MgSO4), evaporated and the residue was dissolved in acetone and the hydrochloride precipitated with ethereal HCI solution.
Recrystallisation from propan-2-ol/ether gave the title compound, hydrochloride (0.6 g) mp 1780C decomp (Found: C, 44.7; H, 3.2; N, 4.2. C12HgCI2NOS.HCI requires C, 44.7; H, 3.1; N, 4.3%).
EXAMPLE 4 2-(((4-Fluorophen yI)sulphin yI)me th yI)p yridine A) 4-Fluorobenzenethiol (5 g) was added to a solution of sodium hydroxide (3.14 g) in ethanol (50 ml) and the resulting solution was treated with 2-picolyl chloride, hydrochloride (6.4 g) in ethanol (25 ml) and the mixture was stirred for 6 hours at ambient temperature. The mixture was filtered, the solvent removed by evaporation and the residue was converted into the hydrochloride with ethereal
HCI. Recrystallisation from ethanol-ether gave 2-(((4-fluorophenyl)thio)methyl)pyridine, hydrochloride (7 g) mp 1 90-2'C (Found: C, 56.1, H, 4.4; N, 5.2 C12H10FNS.HCl requires C,56.4; H, 4.3; N, 5.4%).
B) A stirred suspension of 2-(((4-fluorophenyl)thio)methyl)pyridine, hydrochloride (2 g) in methylene chloride (50 ml) at OOC was treated portionwise with m-chloroperoxybenzoic acid (1.8 g) over 2 hour. The mixture was allowed to warm to ambient temperature and the mixture was stirred for a further 4 hours. The solution was washed with saturated Na2CO3 solution and water, dried (MgS04) and evaporated. The residue was recrystallised from diisopropyl ether to give the title compound (1.0 g) mp 92--40C (Found: C, 60.9; H, 4.6; N,5.6 C12HloFNOS requires C, 61.3; H, 4.3; N, 5.95%).
EXAMPLE 5 2-(((Pentafluorophenyl)sulph!nyl)methyj)pyr!dine A) Pentafluorothiophenol (5 g) was added to a solution of sodium hydroxide (2.0 g) in ethanol (50 ml) and the resulting solution was treated with a solution of 2-picolyl chloride, hydrochloride (4.1 g) in ethanol (25 ml). The mixture was stirred at ambient temperature for 4 hours, filtered through Kieselghur and the solvent removed by evaporation. The residue was converted into the hydrochloride with ethereal HCI solution and this was recrystallised from acetone -- ether to give 2 (((pentafluorophenyl)thio)methyl)pyridine, hydrochloride (5.0 g) mp 1 57-80C (Found: C, 44.0; H, 2.4;
N, 4.0; C12H6F5NS.HCl requires C, 44.0; H, 2.15; N, 4.3%).
B) A stirred suspension of 2-(((pentafluorophenyl)thio)methyl)pyridine, hydrochloride (2.0 g) in methylene chloride (50 ml) at OOC was treated portionwise with m-chloroperoxybenzoic acid (1.41 g) over T hour. The mixture was allowed to warm to ambient temperature, sufficient methylene chloride was added to form a solution, and the mixture was stirred a further + hour. The solution was washed with saturated Na2CO3 solution and water, dried (MgSO4) and evaporated. The residue was converted into the hydrochloride in acetone with ethereal HCI solution to give the title compound, hydrochloride (1.3 g) mp 1 54-60C (Found: C, 41.6; H, 2.15; N, 3.8 C2H"F5NOS.HCí requires C, 41.9; H, 2.05; N, 4.1%).
EXAMPLE 6 2- 3-Trifluoromethylphenyl)sulphinyl)methyl)pyridine A) m-Trifluoromethylbenzenethiol (5 g) was added to a solution of NaOH (2.25 g) in ethanol (50 ml) and the resulting solution was treated with a solution of 2-picolyl chloride, hydrochloride (4.6 g) in ethanol (25 ml) and the mixture was stirred for 5 hours. The resulting suspension was filtered through kieselguhr and the solvent was removed by evaporation. The residue was converted into the hydrochloride in ether with ethereal HCl and recrystallised From acetone-ether to give 2-(((3 trifluoromethylphenyl)thio)methyl)pyridine hydrochloride (4.8 g) mp 145-60C (Found: C, 51.1; H, 4.0;
N, 4.7 C13H10F3NS.HCl requires C, 51.0; H, 3.6; N, 4.6%).
B) A stirred suspension of 2-(((3-trifluoromethylphenyl)thio) methylpyridine, hydrochloride (2.0 g) in methylene chloride (50 ml) at OOC was treated porionwise with m-chloroperoxybenzoic acid (1.5 g) over T hour. The mixture was allowed to warm to ambient temperature and the mixture was stirred a further > hour. The solution was washed with saturated Na2CO3 solution and water, dried (MgSO4) and evaporated. The residue was converted into the hydrochloride, in acetone with ethereal HCI solution, which was recrystallised from acetone-ether to give the title compound, hydrochloride (1.0 g) mp 1 35-60C. (Found: C, 48.3; H, 3.7; N, 4.0 C13H10F3NOS.HCl requires C, 48.4; H, 3.45; N, 4.35%).
EXAMPLE 7 2-Methyl-6-{Kphenylsulphinyl)methyl)pyridine A) Following the method of Example 1A thiophenol is reacted with 6-methyl-2-picolyl chloride hydrochloride in the presence of sodium ethoxide to give 2-methyl-6-((phenylthio)methyl)pyridine.
B) A solution of 2-methyl-6-((phenylthio)methyl) pyridine is reacted with m-chloroperoxybenzoic acid according to the method of Example 1 B to give the title compound.
Pharmacological Test Results
Compound Stress-induced [Product of erosion Anti-secretory Example No] (Senay & Levine) (Shay et al) Dose r % Dose r % change mg/kg inhibition mg/kg in vol 1B 100 60 30 -50 30 NS 2B 100 NS 30 -41 3B 100 64 30 -40 30 NS 4B 100 64 30 -35NS 30 NS 5B 100 73 30 -53 30 73 6B 100 64 30 NS 30 NS NS = not significant
Pharmaceutical Compositions
The following examples illustrate the preparation of unit dosage form of pharmaceutical compositions according to the invention.
EXAMPLE A
Antacid Tablet (chewable)
Saccharin 1.0 mg
Hydrated alumina sucrose powder 750.0 mg 2-((Phenylsulphinylmethyl)pyridine)hydrochloride 100.0 mg
Mannitol BP 170.0 mg
Maize starch BP dried 30.0 mg
Talc purified BP 28.0 mg
Magnesium stearate BP 20.0 mg
Peppermint oil BP 1.0 mg
1100.0 mg
Antacid tablets of the above formulation are prepared by the following procedure. Triturate peppermint oil with talc (screen 40 mesh). Add the triturate, and other ingredients to a blender and mix thoroughly. Slug the powder to large hard slugs. Granulate the slugs through a 14 mesh screen.
Compress the granules on a suitable compression machine to give tablets of the required size.
EXAMPLE B
Anti-ulcer tablet (without antacid) mg/tablet 2-((Phenylsulphinylmethyl)pyridine 1b0.0 mg
Celutab 147.5 mg
Mg Stearate 2.5 mg
250.0 mg
The tablets are prepared by the following method. Blend the ingredients in a suitable blender.
Compress the blended ingredients on a suitable compression machine to form tablets of the above composition. Celutab is a commercial product comprising 90-2% dextrose, 3-5% maltose, the remainder being higher glucose saccharides. The product is spray crystallised.
EXAMPLE C to G
Example A is repeated but replacing 2-((phenylsulphinylmethyl)pyridine)hydrochloride with 100 mg of the products of Examples 2B, 3B, 4B, 5B, and 6B respectively.
EXAMPLES H to M
Example B is repeated but replacing 2-((phenylsulphinylmethyl)pyridine)hydrochloride with 100 mg of the products of Examples 2B to 6B respectively.
The invention also concerns novel intermediates of formula Il
wherein R, R', R2 and n are as defined in connection with formula I and at least one of R, R' and R2 is other than hydrogen, and the pharmaceutically acceptable acid addition salts thereof.
Claims (31)
1. A compound of formula I
wherein R represents hydrogen, lower alkyl, aryl or aralkyl, R1 represents hydrogen or fluorine, R2 represents hydrogen, fluorine, chlorine, or trifluoromethyl, n is 1 or 2, and pharmaceutically acceptable acid addition salts thereof.
2. A compound as claimed in Claim 1, wherein R is hydrogen, R' represents hydrogen or fluorine,
R2 represents hydrogen, fluorine, chlorine or trifluoromethyl, n is 1 or 2 or a pharmaceutically acceptable acid addition salt thereof.
3. 2-(Phenylsulphinylmethyl)pyridine or a pharmaceutically acceptable acid addition salt thereof.
4. 2-(((4-Chlorophenyl)sulphinyl)methyl)-pyridine or a pharmaceutically acceptable acid addition salt thereof.
5.2-(((3,4-Dichlorophenyl)sulphinyl)methyl)-pyridine or a pharmaceutically acceptable acid addition salt thereof.
6. 2-(((Fluorophenyl)sulphinyl)methyl)pyridine or a pharmaceutically acceptable acid addition salt thereof.
7.2-(((Pentafluorophenyl)sulphinyl)methyl)pyridine or a pharmaceutically acceptable acid addition salt thereof.
8. 2-(((3-Trifluoromethylphenyl)sulphinyl)methyl) pyridine or a pharmaceutically acceptable acid addition salt thereof.
9. A compound as claimed in Claim 1, substantially as described in any one of Examples 1 B, 2B, 3B, 4B, SB, 6B or 7B.
10. A pharmaceutical composition comprising a compound as claimed in any one of claims 1-9, and a pharmaceutically acceptable carrier.
11. A pharmaceutical composition as claimed in Claim 10 in unit dosage form.
1 2. A pharmaceutical composition as claimed in Claim 11 in the form of a tablet or capsule.
13. A pharmaceutical composition as claimed in Claim 10 substantially as described in any one of
Examples A to M.
14. A compound as claimed in any one of claims 1 to 9 for use in the treatment of ulcers or hypersecretion.
1 5. A compound of formula Il
wherein R represents hydrogen, loweralkyl, aryl or aralkyl, R' represents hydrogen or fluorine, R2 represents hydrogen, fluorine, chlorine or trifluoromethyl, n is 1 or 2 and at least one of R, R1 and R2 is other than hydrogen, and the pharmaceutically acceptable acid addition salts thereof.
16. 2-(((4-Chlorophenyl)thio)methyl)pyridine or a pharmaceutically acceptable acid addition salt thereof.
1 7. 2-(((3,4-Dichlorophenyl)thio)methyl)pyridine or a pharmaceutically acceptable acid addition salt thereof.
18. 2-(((4-Fluorophenyl)thio)methyl)pyridine or a pharmaceutically acceptable acid addition salt thereof.
1 9. 2-(((Pentafluorophenyl)thio)methyl)pyridine or a pharmaceutically acceptable acid addition salt thereof.
20. 2-(((3-Trifluoromethylphenyl)thio)methyl)pyridine or a pharmaceutically acceptable acid addition salt thereof.
21. A compound as claimed in Claim 1 5 substantially as hereinbefore described in any one of
Examples 2A. 3A, 4A, 5A, 6A or 7A.
22. A process for preparing a compound as claimed in Claim 1, which comprises oxidising a corresponding compound of formula ll
or an acid addition salt thereof wherein R, Rl, R2 and n are as defined in Claim 1, and if desired or necessary converting the product to an acid addition salt.
23. A process as claimed in Claim 22 wherein the oxidising agent is a per acid.
24. A process as claimed in Claim 23, wherein the oxidising agent is m-chloroperbenzoic acid.
25. A process as claimed in any one of claims 22 to 24, wherein the compound prepared is a compound as claimed in any one of claims 1 to 8.
26. A process as claimed in Claim 22, substantially as hereinbefore described in any one of
Examples 1 B, 2B, 3B, 4B, SB or 6B.
27. A compound of formula I, whenever prepared by a process as claimed in any one of claims 22 to 26.
28. A process for preparing a compound of formula ll as claimed in Claim 15, or a pharmaceutically acceptable acid additions salt thereof, which process comprises reacting a thiol compound of formula Ill, or an alkali-metal salt thereof
wherein R' and R2 are as defined in Claim 15, with a pyridine derivative of formula IV
wherein n is 1 or 2 and Hal is a halogen atom, especially chlorine, bromine or iodine and R is as defined in Claim 1 5, and if desired converting the product to an acid addition salt.
29. A process as claimed in Claim 28, wherein the compound of formula Il which is prepared is a compound as claimed in any one of claims 16 to 20.
30. A process as claimed in Claim 28, substantially as hereinbefore described in any one of
Examples 2A, 3A, 4A, 5A or 6A.
31. A compound of formula II, whenever prepared by a process as claimed in any one of claims 28 to 30.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8104411A GB2069492B (en) | 1980-02-20 | 1981-02-12 | Sulphur compounds |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8005668 | 1980-02-20 | ||
| GB8104411A GB2069492B (en) | 1980-02-20 | 1981-02-12 | Sulphur compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB2069492A true GB2069492A (en) | 1981-08-26 |
| GB2069492B GB2069492B (en) | 1984-02-29 |
Family
ID=26274568
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB8104411A Expired GB2069492B (en) | 1980-02-20 | 1981-02-12 | Sulphur compounds |
Country Status (1)
| Country | Link |
|---|---|
| GB (1) | GB2069492B (en) |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0146370A2 (en) * | 1983-12-16 | 1985-06-26 | JOHN WYETH & BROTHER LIMITED | Imidazoquinolines containing other heterocyclic groups |
| EP0146369A2 (en) * | 1983-12-16 | 1985-06-26 | JOHN WYETH & BROTHER LIMITED | Imidazoquinoline derivatives |
| FR2578540A1 (en) * | 1985-03-08 | 1986-09-12 | Leo Pharm Prod Ltd | NOVEL DERIVATIVES OF PYRIDYLMETHOXY- AND -METHYLMERCAPTOANILINES, USED IN PARTICULAR AS ANTIASTHMATICS, THEIR MANUFACTURE AND MEDICAMENTS CONTAINING SAME |
| US4631287A (en) * | 1985-04-16 | 1986-12-23 | Usv Pharmaceutical Corp. | Aryl and heteroaryl ethers as agents for the treatment of hypersensitive ailments |
| US4703044A (en) * | 1983-12-16 | 1987-10-27 | John Wyeth & Brother Limited | Imidazoquinolines containing other heterocyclic groups, useful as anti-ulcer or anti-secretory agents |
| FR2645536A1 (en) * | 1989-04-10 | 1990-10-12 | Rhone Poulenc Agrochimie | HERBICIDAL COMPOUNDS AND COMPOSITIONS CONTAINING SAME |
| 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 |
-
1981
- 1981-02-12 GB GB8104411A patent/GB2069492B/en not_active Expired
Cited By (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4703044A (en) * | 1983-12-16 | 1987-10-27 | John Wyeth & Brother Limited | Imidazoquinolines containing other heterocyclic groups, useful as anti-ulcer or anti-secretory agents |
| EP0146369A2 (en) * | 1983-12-16 | 1985-06-26 | JOHN WYETH & BROTHER LIMITED | Imidazoquinoline derivatives |
| EP0146369A3 (en) * | 1983-12-16 | 1986-04-16 | John Wyeth & Brother Limited | Imidazoquinoline derivatives |
| EP0146370A3 (en) * | 1983-12-16 | 1986-04-23 | John Wyeth & Brother Limited | Imidazoquinolines containing other heterocyclic groups |
| EP0146370A2 (en) * | 1983-12-16 | 1985-06-26 | JOHN WYETH & BROTHER LIMITED | Imidazoquinolines containing other heterocyclic groups |
| FR2578540A1 (en) * | 1985-03-08 | 1986-09-12 | Leo Pharm Prod Ltd | NOVEL DERIVATIVES OF PYRIDYLMETHOXY- AND -METHYLMERCAPTOANILINES, USED IN PARTICULAR AS ANTIASTHMATICS, THEIR MANUFACTURE AND MEDICAMENTS CONTAINING SAME |
| US4631287A (en) * | 1985-04-16 | 1986-12-23 | Usv Pharmaceutical Corp. | Aryl and heteroaryl ethers as agents for the treatment of hypersensitive ailments |
| FR2645536A1 (en) * | 1989-04-10 | 1990-10-12 | Rhone Poulenc Agrochimie | HERBICIDAL COMPOUNDS AND COMPOSITIONS CONTAINING SAME |
| US5123953A (en) * | 1989-04-10 | 1992-06-23 | Rhone-Poulenc Agrochimie | Dihalogenated herbicidal sulphones |
| EP0398818A1 (en) * | 1989-04-10 | 1990-11-22 | Rhone-Poulenc Agrochimie | Dihalogenated herbicidal sulfones |
| 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 |
|---|---|
| GB2069492B (en) | 1984-02-29 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PE20 | Patent expired after termination of 20 years |
Effective date: 20010211 |