CA2078700C - Imidazolylmethyl-pyridines - Google Patents
Imidazolylmethyl-pyridines Download PDFInfo
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- CA2078700C CA2078700C CA002078700A CA2078700A CA2078700C CA 2078700 C CA2078700 C CA 2078700C CA 002078700 A CA002078700 A CA 002078700A CA 2078700 A CA2078700 A CA 2078700A CA 2078700 C CA2078700 C CA 2078700C
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- compound
- alkyl
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- 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
- C07D401/06—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 carbon chain containing only aliphatic carbon atoms
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Neurosurgery (AREA)
- Veterinary Medicine (AREA)
- Neurology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Psychiatry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hospice & Palliative Care (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Polymers With Sulfur, Phosphorus Or Metals In The Main Chain (AREA)
- Luminescent Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
Compounds of formula I, (see formula I) wherein R1 to R4 possess the significances given in the description, may be used in the treatment of senile dementia, Alzheimer's disease and depression.
Description
recv inn ~s~~t I!lIDAZOLYL?iETHYL-PYRIDINES
The present invention relates to imidazolylmethyl-pyridines, their production, their use as pharmaceuticals and pharmaceutical compositions containing them.
More particularly the present invention provides compounds of formula I, N _N
(I) wherein R1 is alkyl (1-4 C), halogen with an atomic number of 9 to 35 or amino optionally mono- or disubstituted by alkyl (1-4 C), Rz and R3 independently of one another are hydrogen or alkyl (1-4 C) and R9 is hydrogen, hydroxy, alkyl (1-4 C), alkoxy (1-4 C) or halogen with an atomic number of 9 to 35, in free base or acid addition salt form, hereinafter referred to as new compounds.
The present invention relates to imidazolylmethyl-pyridines, their production, their use as pharmaceuticals and pharmaceutical compositions containing them.
More particularly the present invention provides compounds of formula I, N _N
(I) wherein R1 is alkyl (1-4 C), halogen with an atomic number of 9 to 35 or amino optionally mono- or disubstituted by alkyl (1-4 C), Rz and R3 independently of one another are hydrogen or alkyl (1-4 C) and R9 is hydrogen, hydroxy, alkyl (1-4 C), alkoxy (1-4 C) or halogen with an atomic number of 9 to 35, in free base or acid addition salt form, hereinafter referred to as new compounds.
Insofar as above-defined alkyl or alkoxy groups are present in the new compounds, these preferably have one or two carbon atoms and especially signify methyl or methoxy.
The imidazolylmethyl radical is preferably in position 2 of the pyridine.
R1 is preferably methyl. Rz and R3 are preferably each hydrogen. R9 is preferably hydrogen. The compound of Example 1 is preferred.
In a particular group of new compounds, R1 is alkyl (1-4 C), RZ and R3 independently of one another are hydrogen or alkyl (1-4 C) and R~, is hydrogen, alkyl (1-4 C) or halogen with an atomic number of 9 to 35.
In accordance with the invention, the new compounds are obtained by reacting a compound of formula II, /N \X
(II) R~
wherein R4 is defined as above, and X is halogen, with a compound of formula III, Rl HN N
(III) wherein R1, RZ and R3 are defined as above, P
The imidazolylmethyl radical is preferably in position 2 of the pyridine.
R1 is preferably methyl. Rz and R3 are preferably each hydrogen. R9 is preferably hydrogen. The compound of Example 1 is preferred.
In a particular group of new compounds, R1 is alkyl (1-4 C), RZ and R3 independently of one another are hydrogen or alkyl (1-4 C) and R~, is hydrogen, alkyl (1-4 C) or halogen with an atomic number of 9 to 35.
In accordance with the invention, the new compounds are obtained by reacting a compound of formula II, /N \X
(II) R~
wherein R4 is defined as above, and X is halogen, with a compound of formula III, Rl HN N
(III) wherein R1, RZ and R3 are defined as above, P
and recovering the resulting compound of formula I in free base form or in acid addition salt form.
The reaction of the compound of formula II with the compound of formula II may take place in known manner, in a solvent which is inert under the reaction conditions, e.g. in dimethylformamide or a lower alcohol. In formula II, X is preferably chlorine.
Working up of the reaction mixtures obtained and purification of the compounds of formula I thus produced may take place in accordance with known methods.
The compounds of formula I may be present in free form or in the form of their acid addition salts. Acid addition salts may be produced from the free bases in known manner, and vice versa.
The starting compounds of formulae II and III are known or may be produced in accordance with known processes, resp. analogously to known processes.
The compounds of formula I and their physiologically acceptable salts, hereinafter referred to as compounds according to the invention, exhibit interesting pharmacological activities and may therefore be used as pharmaceuticals.
In the sieep/wake cycle of the long-term implanted rat [for the method, see J.-M. Vigouret et al., J. Pharmacol 10, 503 (1978)], the compounds according to the invention when administered at 1 to 100 mg/kg p.o. effect an increase in vigilance by prolonging the wake phases.
~ ~'~ ~'~ ~;
The reaction of the compound of formula II with the compound of formula II may take place in known manner, in a solvent which is inert under the reaction conditions, e.g. in dimethylformamide or a lower alcohol. In formula II, X is preferably chlorine.
Working up of the reaction mixtures obtained and purification of the compounds of formula I thus produced may take place in accordance with known methods.
The compounds of formula I may be present in free form or in the form of their acid addition salts. Acid addition salts may be produced from the free bases in known manner, and vice versa.
The starting compounds of formulae II and III are known or may be produced in accordance with known processes, resp. analogously to known processes.
The compounds of formula I and their physiologically acceptable salts, hereinafter referred to as compounds according to the invention, exhibit interesting pharmacological activities and may therefore be used as pharmaceuticals.
In the sieep/wake cycle of the long-term implanted rat [for the method, see J.-M. Vigouret et al., J. Pharmacol 10, 503 (1978)], the compounds according to the invention when administered at 1 to 100 mg/kg p.o. effect an increase in vigilance by prolonging the wake phases.
~ ~'~ ~'~ ~;
Moreover after administration of 1 to 100 mg/kg p.o. to rats with bilateral lesions of the Locus coeruleus (LC) and the Nucleus basalis Meynert (NBM), the compounds according to the invention improve significantly the cognitive performance as measured by the ability to avoid an electric shock in the shuttle box.
The method is similar to that described by V. Haroutunian et al. in Brain Research SU7 (1990) 261 - 266. Male OFA rats (300 g) are anaesthetized with pentobarbital and positioned in a stereotaxic apparatus with the upper incisor bar set 5 mm (LC) or 3.3 rnm (NBM) below the interaural line. The lesions are carried out with a radia frequency lesion generator ar 60 ° C during 10 seconds. 5 weeks after lesioning, behavioral testing is performed, using the active avoidance test in the shuttle box as described by A.R. Dravid, A.-L. Jaton and E.B. Van Deusen in Experimental Brain Research, suppl. 13, p. 249 (1986).
The compounds according to the invention are therefore useful for the treatment of senile dementia, Alzheimer's disease and further degenerative diseases such as Huntington's chorea, Morbus Parkinson, Steel-Richardson syndrome, tardive dyskinesias, hyperkinesia, acute confusion disorders, Down's syndrome, myasthenia gravis and Friedrich's ataxia, furthermore as antidepressants.
An indicated daily dosage is in the range from about 1 mg to about 100 mg of a compound according to the invention, conveniently administered, for example, in divided doses up to four tunes a day.
'fhe compounds according to the invention may be administered by any conventional route, in particular enterally, preferably orally, for example in the form of tablets or capsules, or parenterally, for example in the form of injectable solutions or suspensions.
~~~~~G' In accordance with the foregoing, the present invention also provides a compound according to the invention, for use as a pharmaceutical, e.g. for the treatment of senile dementia, Alzheimer's disease and further degenerative diseases such as Huntington's chorea, Morbus Parkinson, Steel-Richardson syndrome, tardive dyskinesias, hyperkinesia, acute confusion disorders, Down's syndrome, myasthenia gravis and Friedrich's ataxia, and for the treatment of depression.
The present invention furthermore provides a pharmaceutical composition cornprising a compound according to the invention in association with at least one pharmaceutical carrier or diluent. Such compositions may be manufactured in conventional manner. Unit dosage forms contain, for example, from about 0.25 mg to about 50 mg of a compound according to this invention.
The following examples illustrate the invention. The temperatures are given in degrees Celsius and are uncorrected.
The method is similar to that described by V. Haroutunian et al. in Brain Research SU7 (1990) 261 - 266. Male OFA rats (300 g) are anaesthetized with pentobarbital and positioned in a stereotaxic apparatus with the upper incisor bar set 5 mm (LC) or 3.3 rnm (NBM) below the interaural line. The lesions are carried out with a radia frequency lesion generator ar 60 ° C during 10 seconds. 5 weeks after lesioning, behavioral testing is performed, using the active avoidance test in the shuttle box as described by A.R. Dravid, A.-L. Jaton and E.B. Van Deusen in Experimental Brain Research, suppl. 13, p. 249 (1986).
The compounds according to the invention are therefore useful for the treatment of senile dementia, Alzheimer's disease and further degenerative diseases such as Huntington's chorea, Morbus Parkinson, Steel-Richardson syndrome, tardive dyskinesias, hyperkinesia, acute confusion disorders, Down's syndrome, myasthenia gravis and Friedrich's ataxia, furthermore as antidepressants.
An indicated daily dosage is in the range from about 1 mg to about 100 mg of a compound according to the invention, conveniently administered, for example, in divided doses up to four tunes a day.
'fhe compounds according to the invention may be administered by any conventional route, in particular enterally, preferably orally, for example in the form of tablets or capsules, or parenterally, for example in the form of injectable solutions or suspensions.
~~~~~G' In accordance with the foregoing, the present invention also provides a compound according to the invention, for use as a pharmaceutical, e.g. for the treatment of senile dementia, Alzheimer's disease and further degenerative diseases such as Huntington's chorea, Morbus Parkinson, Steel-Richardson syndrome, tardive dyskinesias, hyperkinesia, acute confusion disorders, Down's syndrome, myasthenia gravis and Friedrich's ataxia, and for the treatment of depression.
The present invention furthermore provides a pharmaceutical composition cornprising a compound according to the invention in association with at least one pharmaceutical carrier or diluent. Such compositions may be manufactured in conventional manner. Unit dosage forms contain, for example, from about 0.25 mg to about 50 mg of a compound according to this invention.
The following examples illustrate the invention. The temperatures are given in degrees Celsius and are uncorrected.
EXAHPLE l: (2-(2-methylimidazol-1-yl)methyl]pyridine 9.7 g (75 mM) of 2-(chloromethyl)pyridine and 42 g (512 mM) of 2-methyl-imidazole are suspended in 40 ml dimethylformamide, then stirred for 3 hours at 105 °. The dimethylformamide is distilled off and the crystalline residue is diluted with ethyl acetate and a little hexane. Following filtration, the mother solution is concentrated by evaporation and the dimethylformamide distilled off, and then shaken out several times between water and methylene chloride. 10.3 g of the oily title cornpound are obtained.
9.3 g of the obtained basa_ i.n ethanol are mixed with 12.7 g of furnaric acid. The resulting bis(base)-tris(hydrogen fumarate)crystallizes from ethanol/ethyl acetate and is recrystallized once from ethanol/ethyl acetate. It is uniform upon thin-layer chromatography and melts at 109 - 110 °.
The following [2-(imidazol-1-yl)methyl]pyridines are produced analogously to example 1:
~Example R I R4 M.p.
I
i T ~
I ~
~ ~ ~
I 3 I CH3 CH3 H H I 250 - 253 (decomp.) I I **
I 4 I CE33 H CH3 I H 213 - 220 (decomp.) I I I **
m * fumarate ** dihydrochloride ~~~~~~~~!
9.3 g of the obtained basa_ i.n ethanol are mixed with 12.7 g of furnaric acid. The resulting bis(base)-tris(hydrogen fumarate)crystallizes from ethanol/ethyl acetate and is recrystallized once from ethanol/ethyl acetate. It is uniform upon thin-layer chromatography and melts at 109 - 110 °.
The following [2-(imidazol-1-yl)methyl]pyridines are produced analogously to example 1:
~Example R I R4 M.p.
I
i T ~
I ~
~ ~ ~
I 3 I CH3 CH3 H H I 250 - 253 (decomp.) I I **
I 4 I CE33 H CH3 I H 213 - 220 (decomp.) I I I **
m * fumarate ** dihydrochloride ~~~~~~~~!
as well as the following [4-(imidazol-1-y1)methyl]pyridine:
Example ~ Rz R3 R9 M.p.
R1 ~ ~ ~ ~
i i i i i i ~ CH3 ~ H H H ~ 155 - 156 *
~ ~
* fumarate
Example ~ Rz R3 R9 M.p.
R1 ~ ~ ~ ~
i i i i i i ~ CH3 ~ H H H ~ 155 - 156 *
~ ~
* fumarate
Claims (8)
1. A process for the production of a compound of formula I, wherein R1 is alkyl (1-4 C), halogen with an atomic number of 9 to 35 or amino optionally mono- or disubstituted by alkyl (1-4 C), R2 and R3 independently of one another are hydrogen or alkyl (1-4 C) and R4 is hydrogen, hydroxy, alkyl (1-4 C), alkoxy (1-4 C) or halogen with an atomic number of 9 to 35, in free base or acid addition salt form, which includes the step of reacting a compound of formula II, wherein R4 is defined as above, and X is halogen, with a compound of formula III, wherein R1, R2 and R3 are defined as above, and recovering the resulting compound of formula I in free base form or in acid addition salt form.
2. A compound of formula I in free base form or acid addition salt form, as defined in claim 1.
3. A compound of claim 2 wherein R1 is alkyl (1-4 C), R2 and R3 independently of one another are hydrogen or alkyl (1-4 C) and R4 is hydrogen, alkyl (1-4 C) or halogen with an atomic number of 9 to 35, in free base or acid addition salt form.
4. A compound of claim 2. which is the [2-(2-methylimidazol-1-yl)methyl]pyridine, in free base or acid addition salt form.
5. A compound of claim 4 in acid addition salt form, wherein the acid is fumaric acid.
6. A compound of claim 2 wherein - R1 = CH3, R2 = H, R3 = H, R4 = 6-CH3, or - R1 = CH3, R2 = CH3, R4 = H, R4 = H, or - R1 = CH3, R2 = H, R3 = CH3, R4 = H, and the imidazolylmethyl group is in position 2, or - R1 = CH3, R2 = H, R3 = H, R4 = H
and the imidazolylmethyl group is in position 4, in free base or acid addition salt form.
and the imidazolylmethyl group is in position 4, in free base or acid addition salt form.
7. A compound of any one of claims 2 to 6 in physiologically acceptable form, for use in the treatment of senile dementia, Alzheimer's disease, Huntington's chorea, Morbus Parkinson, Steel-Richardson syndrome, tardive dyskinesia, hyperkinesia, acute confusion disorders, Down's syndrome, myasthenia gravis or Friedrich's ataxia, or in the treatment of depression.
8. A pharmaceutical composition comprising a compound according to any one of claims 2 to 6 in physiologically acceptable form, in association with a pharmaceutical carrier or diluent.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEP4131584.7 | 1991-09-23 | ||
| DE4131584A DE4131584A1 (en) | 1991-09-23 | 1991-09-23 | IMIDAZOLYLMETHYL-PYRIDINE, THEIR PRODUCTION AND USE AS A PHARMACEUTICAL |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2078700A1 CA2078700A1 (en) | 1993-03-24 |
| CA2078700C true CA2078700C (en) | 2005-09-13 |
Family
ID=6441240
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002078700A Expired - Fee Related CA2078700C (en) | 1991-09-23 | 1992-09-21 | Imidazolylmethyl-pyridines |
Country Status (24)
| Country | Link |
|---|---|
| EP (1) | EP0534904B1 (en) |
| JP (1) | JP2568356B2 (en) |
| KR (1) | KR100254085B1 (en) |
| AT (1) | ATE144509T1 (en) |
| AU (1) | AU650569B2 (en) |
| CA (1) | CA2078700C (en) |
| CZ (1) | CZ281675B6 (en) |
| DE (2) | DE4131584A1 (en) |
| DK (1) | DK0534904T3 (en) |
| ES (1) | ES2092666T3 (en) |
| FI (1) | FI103887B (en) |
| GR (1) | GR3021444T3 (en) |
| HU (2) | HUT61993A (en) |
| IL (1) | IL103229A (en) |
| MX (1) | MX9205365A (en) |
| MY (1) | MY110450A (en) |
| NO (1) | NO301162B1 (en) |
| NZ (1) | NZ244420A (en) |
| RO (1) | RO109337B1 (en) |
| RU (1) | RU2058312C1 (en) |
| SG (1) | SG43079A1 (en) |
| SK (1) | SK289692A3 (en) |
| TW (1) | TW222630B (en) |
| ZA (1) | ZA927279B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018217631A1 (en) * | 2017-05-22 | 2018-11-29 | Torrey Pines Institute For Molecular Studies | Compositions, methods of use, and methods of treatment |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH10165349A (en) * | 1996-12-06 | 1998-06-23 | Matsushita Electric Ind Co Ltd | Dish washer |
| DE10000161A1 (en) * | 2000-01-06 | 2001-07-19 | Boehringer Ingelheim Pharma | Determining test substances that inhibit protease, involves incubating cells expressing fusion protein having substrate with cleavage site for protease and reporter, measuring cleaved reporter and comparing with standard |
| GB0009037D0 (en) * | 2000-04-13 | 2000-05-31 | Novartis Ag | Organic compounds |
| NZ565763A (en) * | 2005-07-29 | 2010-12-24 | Vanda Pharmaceuticals Inc | Method of improving wakefulness |
| JP5044572B2 (en) * | 2006-02-13 | 2012-10-10 | ヴァンダ ファーマシューティカルズ インコーポレイテッド | Stable dosage formulation of imidazolylalkyl-pyridine |
| WO2009097416A1 (en) * | 2008-01-29 | 2009-08-06 | Vanda Pharmaceuticals, Inc. | Imidazolylalkyl- pyridines as dbh inhibitors |
| KR20110071014A (en) | 2008-10-17 | 2011-06-27 | 위스콘신 얼럼나이 리서어치 화운데이션 | Method of making biologically active alpha-beta peptides |
| US9394290B2 (en) * | 2010-10-21 | 2016-07-19 | Universitaet Des Saarlandes Campus Saarbruecken | Selective CYP11B1 inhibitors for the treatment of cortisol dependent diseases |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2862340D1 (en) * | 1978-02-01 | 1983-11-24 | Wellcome Found | Imidazole derivatives and salts thereof, their synthesis, and pharmaceutical formulations thereof |
| GB2028317B (en) * | 1978-08-15 | 1982-11-10 | Pfizer Ltd | 2-(imidazol-1-ylmethyl)-pyridine and -quinoline thromboxane synthetase inhibitors |
| US4634711A (en) * | 1985-08-02 | 1987-01-06 | Smithkline Beckman Corporation | Pyridylalkyl imidazole-2-thiols |
| DE3811574A1 (en) * | 1988-03-31 | 1989-10-19 | Schering Ag | N-SUBSTITUTED IMIDAZOLES, METHODS FOR THEIR PRODUCTION AND THEIR USE IN MEDICINAL PRODUCTS |
-
1991
- 1991-09-23 DE DE4131584A patent/DE4131584A1/en not_active Withdrawn
-
1992
- 1992-09-09 HU HU9202886A patent/HUT61993A/en unknown
- 1992-09-18 MY MYPI92001673A patent/MY110450A/en unknown
- 1992-09-21 AU AU25226/92A patent/AU650569B2/en not_active Ceased
- 1992-09-21 IL IL10322992A patent/IL103229A/en not_active IP Right Cessation
- 1992-09-21 FI FI924233A patent/FI103887B/en not_active IP Right Cessation
- 1992-09-21 AT AT92810719T patent/ATE144509T1/en active
- 1992-09-21 NZ NZ244420A patent/NZ244420A/en not_active IP Right Cessation
- 1992-09-21 NO NO923653A patent/NO301162B1/en not_active IP Right Cessation
- 1992-09-21 SG SG1996003366A patent/SG43079A1/en unknown
- 1992-09-21 EP EP92810719A patent/EP0534904B1/en not_active Expired - Lifetime
- 1992-09-21 DK DK92810719.2T patent/DK0534904T3/en active
- 1992-09-21 CZ CS922896A patent/CZ281675B6/en not_active IP Right Cessation
- 1992-09-21 CA CA002078700A patent/CA2078700C/en not_active Expired - Fee Related
- 1992-09-21 SK SK2896-92A patent/SK289692A3/en not_active IP Right Cessation
- 1992-09-21 DE DE59207425T patent/DE59207425D1/en not_active Expired - Lifetime
- 1992-09-21 ES ES92810719T patent/ES2092666T3/en not_active Expired - Lifetime
- 1992-09-22 KR KR1019920017228A patent/KR100254085B1/en not_active IP Right Cessation
- 1992-09-22 MX MX9205365A patent/MX9205365A/en unknown
- 1992-09-22 RO RO92-01218A patent/RO109337B1/en unknown
- 1992-09-22 RU SU925052552A patent/RU2058312C1/en active
- 1992-09-22 JP JP4252692A patent/JP2568356B2/en not_active Expired - Fee Related
- 1992-09-23 ZA ZA927279A patent/ZA927279B/en unknown
- 1992-09-24 TW TW081107550A patent/TW222630B/zh active
-
1995
- 1995-06-13 HU HU95P/P00198P patent/HU211261A9/en unknown
-
1996
- 1996-10-24 GR GR960402593T patent/GR3021444T3/en unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018217631A1 (en) * | 2017-05-22 | 2018-11-29 | Torrey Pines Institute For Molecular Studies | Compositions, methods of use, and methods of treatment |
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