EP1003752A1 - 3-substituierte 3,4,5,7-tetrahydro-pyrrolo 3',4':4,5] thieno 2,3-d] pyrimidin-derivate, ihre herstellung und verwendung als 5ht-antagonisten - Google Patents
3-substituierte 3,4,5,7-tetrahydro-pyrrolo 3',4':4,5] thieno 2,3-d] pyrimidin-derivate, ihre herstellung und verwendung als 5ht-antagonistenInfo
- Publication number
- EP1003752A1 EP1003752A1 EP98942610A EP98942610A EP1003752A1 EP 1003752 A1 EP1003752 A1 EP 1003752A1 EP 98942610 A EP98942610 A EP 98942610A EP 98942610 A EP98942610 A EP 98942610A EP 1003752 A1 EP1003752 A1 EP 1003752A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- ethyl
- tetrahydro
- thieno
- pyrrolo
- pyrimidin
- 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.)
- Withdrawn
Links
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- UXBDIUBADZDARJ-UHFFFAOYSA-N ethyl 2-(ethoxymethylideneamino)-5-ethyl-6,7-dihydro-4h-thieno[3,2-c]pyridine-3-carboxylate Chemical compound C1CN(CC)CC2=C1SC(N=COCC)=C2C(=O)OCC UXBDIUBADZDARJ-UHFFFAOYSA-N 0.000 description 1
- ZIUSEGSNTOUIPT-UHFFFAOYSA-N ethyl 2-cyanoacetate Chemical compound CCOC(=O)CC#N ZIUSEGSNTOUIPT-UHFFFAOYSA-N 0.000 description 1
- DQYGBMLEVQLDQC-UHFFFAOYSA-N ethyl 3-oxopyrrolidine-1-carboxylate Chemical compound CCOC(=O)N1CCC(=O)C1 DQYGBMLEVQLDQC-UHFFFAOYSA-N 0.000 description 1
- OHUWMXNZLVSOKK-UHFFFAOYSA-N ethyl 7-(2-hydroxyethyl)-8-oxo-1,3-dihydropyrrolo[2,3]thieno[2,4-d]pyrimidine-2-carboxylate Chemical compound N1=CN(CCO)C(=O)C2=C1SC1=C2CN(C(=O)OCC)C1 OHUWMXNZLVSOKK-UHFFFAOYSA-N 0.000 description 1
- XWNGDLOIWXIPGP-UHFFFAOYSA-N ethyl 7-[2-(4-naphthalen-1-ylpiperazin-1-yl)ethyl]-8-oxo-1,3-dihydropyrrolo[2,3]thieno[2,4-d]pyrimidine-2-carboxylate Chemical compound C1=CC=C2C(N3CCN(CC3)CCN3C=NC=4SC=5CN(CC=5C=4C3=O)C(=O)OCC)=CC=CC2=C1 XWNGDLOIWXIPGP-UHFFFAOYSA-N 0.000 description 1
- YDOXKFQSOLLULC-UHFFFAOYSA-N ethyl 7-[2-[4-(2,3-dihydro-1h-inden-4-yl)piperazin-1-yl]ethyl]-8-oxo-1,3-dihydropyrrolo[2,3]thieno[2,4-d]pyrimidine-2-carboxylate Chemical compound O=C1C=2C=3CN(C(=O)OCC)CC=3SC=2N=CN1CCN(CC1)CCN1C1=CC=CC2=C1CCC2 YDOXKFQSOLLULC-UHFFFAOYSA-N 0.000 description 1
- XTIVWXPNPMQFNA-UHFFFAOYSA-N ethyl 7-[2-[4-(2-chlorophenyl)piperazin-1-yl]propyl]-8-oxo-1,3-dihydropyrrolo[2,3]thieno[2,4-d]pyrimidine-2-carboxylate Chemical compound O=C1C=2C=3CN(C(=O)OCC)CC=3SC=2N=CN1CC(C)N(CC1)CCN1C1=CC=CC=C1Cl XTIVWXPNPMQFNA-UHFFFAOYSA-N 0.000 description 1
- XUVVLBWUZCSVQW-UHFFFAOYSA-N ethyl 7-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-8-oxo-1,3-dihydropyrrolo[2,3]thieno[2,4-d]pyrimidine-2-carboxylate Chemical compound O=C1C=2C=3CN(C(=O)OCC)CC=3SC=2N=CN1CCN(CC1)CCN1C1=CC=CC=C1OC XUVVLBWUZCSVQW-UHFFFAOYSA-N 0.000 description 1
- AXADUMDRJYXYOG-UHFFFAOYSA-N ethyl 7-[2-[4-(2-methylnaphthalen-1-yl)piperazin-1-yl]ethyl]-8-oxo-1,3-dihydropyrrolo[2,3]thieno[2,4-d]pyrimidine-2-carboxylate Chemical compound C1=CC=C2C(N3CCN(CC3)CCN3C=NC=4SC=5CN(CC=5C=4C3=O)C(=O)OCC)=C(C)C=CC2=C1 AXADUMDRJYXYOG-UHFFFAOYSA-N 0.000 description 1
- BVKMTRLDZGMOLA-UHFFFAOYSA-N ethyl 7-[2-[4-(2-methylphenyl)piperazin-1-yl]ethyl]-8-oxo-1,3-dihydropyrrolo[2,3]thieno[2,4-d]pyrimidine-2-carboxylate Chemical compound O=C1C=2C=3CN(C(=O)OCC)CC=3SC=2N=CN1CCN(CC1)CCN1C1=CC=CC=C1C BVKMTRLDZGMOLA-UHFFFAOYSA-N 0.000 description 1
- ZWRXAKFXQXOFFG-UHFFFAOYSA-N ethyl 7-[3-[4-(2-cyanophenyl)piperazin-1-yl]propyl]-8-oxo-1,3-dihydropyrrolo[2,3]thieno[2,4-d]pyrimidine-2-carboxylate Chemical compound O=C1C=2C=3CN(C(=O)OCC)CC=3SC=2N=CN1CCCN(CC1)CCN1C1=CC=CC=C1C#N ZWRXAKFXQXOFFG-UHFFFAOYSA-N 0.000 description 1
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- 239000007941 film coated tablet Substances 0.000 description 1
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- 208000037870 generalized anxiety Diseases 0.000 description 1
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- 239000012442 inert solvent Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000006984 memory degeneration Effects 0.000 description 1
- 208000023060 memory loss Diseases 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- KFOPKOFKGJJEBW-ZSSYTAEJSA-N methyl 2-[(1s,7r,8s,9s,10r,13r,14s,17r)-1,7-dihydroxy-10,13-dimethyl-3-oxo-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl]acetate Chemical compound C([C@H]1O)C2=CC(=O)C[C@H](O)[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](CC(=O)OC)[C@@]1(C)CC2 KFOPKOFKGJJEBW-ZSSYTAEJSA-N 0.000 description 1
- 230000004899 motility Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
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- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 208000019906 panic disease Diseases 0.000 description 1
- 229960002296 paroxetine Drugs 0.000 description 1
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- 239000011591 potassium Substances 0.000 description 1
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- 210000001609 raphe nuclei Anatomy 0.000 description 1
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- 239000011780 sodium chloride Substances 0.000 description 1
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- 230000000638 stimulation Effects 0.000 description 1
- IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid Chemical compound NS(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 description 1
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- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D495/14—Ortho-condensed systems
-
- 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
-
- 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
- A61P25/24—Antidepressants
Definitions
- the invention relates to new 3-substituted 3, 4, 5, 7-tetrahydro-pyrrolo [3 ', 4': 4, 5] thieno [2, 3-d] pyrimidine derivatives, their preparation and their use in the preparation of active pharmaceutical ingredients f en.
- SSRIs serotonin reuptake inhibitors
- the antidepressant effect only occurs after a treatment of at least 3 weeks , in addition, about 30% of the patients are resistant to therapy.
- the blockade of presynaptic serotonin autoreceptors increases the release of the serotonin by canceling the negative coupling and thus the current transmitter concentration in the synaptic cleft. This increase in transmitter concentration is considered the antidepressant principle.
- This mechanism of action differs from the previously known antidepressants, which simultaneously activate the 5 presynaptic and somatodendritic autoreceptors and therefore lead to a delayed onset of action only after desensitization of these autoreceptors.
- the direct auto-receptor blockade circumvents this effect.
- the presynaptic serotonin autoreceptor is the 5-HT- B subtype (Fink et al., Arch. Pharmacol. 352 (1995), p. 451). Its selective blockage by S-HTi B / D 'antagonists increases the release of serotonin in the brain: GW Price et al., Behavioral Brain Research 73 (1996), 5 pp. 79-82; PH Hutson et al., Neuropharmacology Vol. 34, No. 4 (1995), pp. 383-392.
- the selective 5-HT- B antagonist GR 127 935 surprisingly reduces the release of serotonin in the cortex after systemic administration.
- One explanation could be the stimulation of somatodendritic 5-HT ⁇ A receptors in the raphe region by the released serotonin, which inhibits the rate of fire of serotonergic neurons and thus the release of serotonin (M. Skingle et al., Neuropharmacology Vol. 34 No. 4 (1995), pp. 377-382, pp. 393-402).
- 5 A strategy to circumvent the auto-inhibitory effects in serotonergic regions of origin follows the blockade of the presynaptic 5-HT 1B receptors. This hypothesis is supported by the observation that the influence of paroxetine on the serotonin release in the dorsal raphe nucleus of the rat by the
- the second strategy involves blocking both types of auto-receptors, namely the 5-HT 1A receptors to increase neuronal firing and the 5-HT 1 B receptors to increase terminal serotonin release (Starkey and Skingle, Neuropharmacology 33. (3-4) (1994), 393).
- 5-HT IB / D "antagonists alone or coupled with a 5-HT- A receptor antagonistic component should therefore increase the release of serotonin in the brain and could therefore include advantages in the therapy of depression and related mental illnesses.
- R 1 is a hydrogen atom, a C 1 -C 4 -alkyl group, an acetyl group, a phenylalkyl C 1 -C 4 radical, the aromatic optionally being replaced by halogen, C 1 -C 4 -alkyl, trifluoromethyl, hydroxy, C 1 -C 4 4 -alkoxy, amino, cyano or nitro groups is substituted or a carboxylic acid C ! -C 3 -alkyl ester residue means
- R 2 is a halogen or CC 4 alkyl, trifluoroethyl, trifluoromethoxy, hydroxy, Ci-CValkoxy, amino, monomethylamino, prostitute hylamino, cyano or nitro groups which are mono- or disubstituted phenyl, pyridyl, optionally by halogen atoms, CC 4 alkyl -, Pyrimidinyl or pyrazinyl group, optionally with a benzene nucleus, optionally by halogen atoms, Ci-CValkyl, hydroxy, tri. fluoromethyl, Ci-C ⁇ -alkoxy, amino, cyano or nitro groups can be mono- or disubstituted and optionally 1 stick Can contain substance atom, or with a 5- or 6-membered
- Ring which can contain 1-2 oxygen atoms, can be fused
- A represents NH or an oxygen atom
- Z represents a nitrogen atom, carbon atom or CH, where the bond between Y and Z can also be a double bond,
- n represents the number 2, 3 or 4,
- R 1 is hydrogen, ethyl, carboxylic acid ethyl ester
- R 2 o-methoxyphenyl, 1-naphthyl, 2-methoxy-1-naphthyl, 2-methyl-1-naphthyl
- Z is a nitrogen atom
- n is the number 2 and 3.
- the compounds of formula I according to the invention can be prepared by using a compound of formula II
- R 1 has the meaning given above
- R 3 represents a cyano group or a C 3 -3 -alkyl-carboxylic acid ester group
- R 4
- C 3 alkyl means with a primary A in the formula III
- R 2 has the meaning given above, and the compound thus obtained is optionally converted into the acid addition salt of a physiologically acceptable acid.
- reaction is conveniently carried out in an inert organic solvent, especially a lower alcohol, e.g. Methanol or ethanol, or a cyclic saturated ether, especially tetrahydrofuran or dioxane.
- a lower alcohol e.g. Methanol or ethanol
- a cyclic saturated ether especially tetrahydrofuran or dioxane.
- the implementation usually takes place at temperatures of
- R 1 has the meaning given above
- R 3 is a cyano group or a C 3 -3 -alkyl-carboxylic acid ester group and R 4 is C 3 -3 -alkyl, with a primary amino alcohol of the formula IV
- halogenating agent e.g.
- the compounds of the formula I according to the invention can either be recrystallized by recrystallization from the customary organic solvents, preferably from a lower alcohol, such as ethanol, or purified by column chromatography.
- the free 3-substituted 3, 4, 5,7-tetrahydro-pyrrolo [3 ', 4': 4,5] thieno [2, 3-d] pyrimidine derivatives of the formula I can in the usual way in the acid addition salts of a solution with the stoichiometric amount of the corresponding acid.
- Pharmaceutically acceptable acids are, for example, hydrochloric acid, phosphoric acid, sulfuric acid, methanesulfonic acid, amidosulfonic acid, maleic acid, fumaric acid, oxalic acid, tartaric acid or citric acid.
- the invention also relates to a therapeutic agent, characterized in that it contains a compound of the formula I or its pharmacologically acceptable acid addition salt as active ingredient in addition to conventional carriers and diluents, and the use of the new compounds in combating diseases.
- the compounds according to the invention can be administered in the usual way orally or parenterally, intravenously or intramuscularly.
- the dosage depends on the age, condition and weight of the patient and on the type of application.
- the daily dose of active substance is between approximately 1 and 100 mg / kg body weight when administered orally and between 0.1 and 10 mg / kg body weight when administered parenterally.
- the new compounds can be used in common galenical application forms, solid or liquid, e.g. as tablets, film-coated tablets, capsules, powders, granules, dragees, suppositories, solutions, ointments, creams or sprays. These are manufactured in the usual way.
- the active ingredients can be processed with the usual pharmaceutical auxiliaries such as tablet binders, fillers, preservatives, tablet disintegrants, flow regulators, plasticizers, wetting agents, dispersants, emulsifiers, solvents, retardants, antioxidants and / or propellants (see H. Sucker et. Al : Pharmaceutical Technology, Thieme-Verlag, Stuttgart, 1978).
- the administration forms obtained in this way normally contain the active ingredient in an amount of 1 to 99% by weight.
- the compounds of the invention have a high affinity for the serotonin receptors 5-HT ⁇ B , 5-HT ⁇ D and 5-HT ⁇ A.
- the affinity for these receptors is approximately the same, at least of the same order of magnitude.
- some of the compounds according to the invention have good serotonin reuptake inhibition - a principle which is implemented in most antidepressants.
- These compounds are suitable as medicaments for the treatment of disease states in which the serotonin concentration is reduced and in which one wishes to block the activity of the presynaptic receptors 5-HT ⁇ B , 5-HT ⁇ A , 5-HTI D as part of a therapy without to strongly influence other receptors. Depression, for example, is such an illness.
- the compounds of the present invention can also be used for
- central nervous disorders such as seasonal mood disorders and dysthymia
- This also includes anxiety such as generalized anxiety, panic attacks, sociophobia, obsessive-compulsive disorders and post-traumatic stress symptoms, memory disorders including dementia, amnesias and age-related memory loss as well as psychogenic eating disorders such as anorexia nervosa and bulimia nervosa.
- the compounds of the invention may also be useful for the treatment of endocrine disorders such as hyperprolactinemia, as well as for the treatment of vascular spasms (particularly the brain vessels), hypertension and gastrointestinal disorders associated with motility and secretion disorders. Another area of application is sexual disorders.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19734444 | 1997-08-08 | ||
| DE19734444A DE19734444A1 (de) | 1997-08-08 | 1997-08-08 | 3-Substituierte 3,4,5,7-Tetrahydro-pyrrolo(3',4':4,5) thieno (2,3-d) pyrimidin-Derivate, ihre Herstellung und Verwendung |
| PCT/EP1998/004633 WO1999007711A1 (de) | 1997-08-08 | 1998-07-23 | 3-substituierte 3,4,5,7-tetrahydro-pyrrolo[3',4':4,5] thieno[2,3-d] pyrimidin-derivate, ihre herstellung und verwendung als 5ht-antagonisten |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP1003752A1 true EP1003752A1 (de) | 2000-05-31 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP98942610A Withdrawn EP1003752A1 (de) | 1997-08-08 | 1998-07-23 | 3-substituierte 3,4,5,7-tetrahydro-pyrrolo 3',4':4,5] thieno 2,3-d] pyrimidin-derivate, ihre herstellung und verwendung als 5ht-antagonisten |
Country Status (25)
| Country | Link |
|---|---|
| US (1) | US6355647B1 (cs) |
| EP (1) | EP1003752A1 (cs) |
| JP (1) | JP2001512734A (cs) |
| KR (1) | KR20010022658A (cs) |
| CN (1) | CN1267303A (cs) |
| AR (1) | AR016594A1 (cs) |
| AU (1) | AU749539B2 (cs) |
| BG (1) | BG104151A (cs) |
| BR (1) | BR9811091A (cs) |
| CA (1) | CA2300391A1 (cs) |
| CO (1) | CO4960665A1 (cs) |
| CZ (1) | CZ290678B6 (cs) |
| DE (1) | DE19734444A1 (cs) |
| HR (1) | HRP980435A2 (cs) |
| HU (1) | HUP0101311A3 (cs) |
| ID (1) | ID24222A (cs) |
| IL (1) | IL134161A0 (cs) |
| NO (1) | NO20000605L (cs) |
| NZ (1) | NZ502657A (cs) |
| PL (1) | PL340726A1 (cs) |
| SK (1) | SK1052000A3 (cs) |
| TR (1) | TR200000371T2 (cs) |
| TW (1) | TW513435B (cs) |
| WO (1) | WO1999007711A1 (cs) |
| ZA (1) | ZA987114B (cs) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US20040048874A1 (en) * | 2001-05-22 | 2004-03-11 | Bardsley Hazel Judith | New therapeutic use of 4-(2-fluorophenyl)-6-methyl-2-(1-piperazinyl)thieno[2,3-D]pyrimidine |
| GB0216027D0 (en) * | 2002-07-10 | 2002-08-21 | Arachnova Therapeutics Ltd | New therapeutic use |
| DE10259382A1 (de) * | 2002-12-18 | 2004-07-01 | Abbott Gmbh & Co. Kg | 3-Substituierte 3,4-Dihydro-thieno[2,3-d]pyrimidin-4-on-Derivate, ihre Herstellung und Verwendung |
| AU2004204825B2 (en) * | 2003-01-13 | 2007-07-19 | Dynogen Pharmaceuticals, Inc. | Method of treating functional bowel disorders |
| DE602004005814T2 (de) * | 2003-01-13 | 2008-01-10 | Dynogen Pharmaceuticals Inc., Waltham | Verfahren zur behandlung von übelkeit, erbrechen, würgereiz oder jede kombination daraus |
| US6846823B2 (en) * | 2003-04-04 | 2005-01-25 | Dynogen Pharmaceuticals, Inc. | Method of treating lower urinary tract disorders |
| US20050165025A1 (en) * | 2004-01-22 | 2005-07-28 | Recordati Ireland Ltd. | Combination therapy with 5HT 1A and 5HT 1B-receptor antagonists |
| US7375814B2 (en) * | 2005-03-11 | 2008-05-20 | Sandia Corporation | Natural gas leak mapper |
| WO2006105117A2 (en) * | 2005-03-28 | 2006-10-05 | Dynogen Pharmaceuticals, Inc. | Method of treating disorders and conditions using peripherally-restricted antagonists and inhibitors |
| WO2020183011A1 (en) | 2019-03-14 | 2020-09-17 | Institut Curie | Htr1d inhibitors and uses thereof in the treatment of cancer |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5001130A (en) | 1988-02-18 | 1991-03-19 | Bristol-Myers Company | Psychotropic heterobicycloalkylpiperazine derivatives |
| US4835157A (en) | 1988-03-15 | 1989-05-30 | Ortho Pharmaceutical Corporation | Thieno- and furopyrimidine-2,4-dione piperidine derivatives as serotonin antagonists and alpha adrenergic blocking agents |
| DE19636769A1 (de) | 1996-09-10 | 1998-03-12 | Basf Ag | 3-Substituierte Pyrido [4',3':4,5]thieno[2,3-d]pyrimidin-Derivate, ihre Herstellung und Verwendung |
-
1997
- 1997-08-08 DE DE19734444A patent/DE19734444A1/de not_active Withdrawn
-
1998
- 1998-07-23 EP EP98942610A patent/EP1003752A1/de not_active Withdrawn
- 1998-07-23 AU AU90683/98A patent/AU749539B2/en not_active Ceased
- 1998-07-23 NZ NZ502657A patent/NZ502657A/en unknown
- 1998-07-23 JP JP2000506214A patent/JP2001512734A/ja active Pending
- 1998-07-23 SK SK105-2000A patent/SK1052000A3/sk unknown
- 1998-07-23 IL IL13416198A patent/IL134161A0/xx unknown
- 1998-07-23 WO PCT/EP1998/004633 patent/WO1999007711A1/de not_active Application Discontinuation
- 1998-07-23 CA CA002300391A patent/CA2300391A1/en not_active Abandoned
- 1998-07-23 ID IDW20000239A patent/ID24222A/id unknown
- 1998-07-23 HU HU0101311A patent/HUP0101311A3/hu unknown
- 1998-07-23 PL PL98340726A patent/PL340726A1/xx not_active Application Discontinuation
- 1998-07-23 CZ CZ2000462A patent/CZ290678B6/cs not_active IP Right Cessation
- 1998-07-23 CN CN98808009A patent/CN1267303A/zh active Pending
- 1998-07-23 KR KR1020007001252A patent/KR20010022658A/ko not_active Withdrawn
- 1998-07-23 BR BR9811091-8A patent/BR9811091A/pt not_active IP Right Cessation
- 1998-07-23 TR TR2000/00371T patent/TR200000371T2/xx unknown
- 1998-07-23 US US09/485,188 patent/US6355647B1/en not_active Expired - Lifetime
- 1998-08-06 HR HR19734444.5A patent/HRP980435A2/hr not_active Application Discontinuation
- 1998-08-07 AR ARP980103914A patent/AR016594A1/es not_active Application Discontinuation
- 1998-08-07 TW TW087113048A patent/TW513435B/zh active
- 1998-08-07 ZA ZA9807114A patent/ZA987114B/xx unknown
- 1998-08-10 CO CO98045546A patent/CO4960665A1/es unknown
-
2000
- 2000-02-07 NO NO20000605A patent/NO20000605L/no not_active Application Discontinuation
- 2000-02-10 BG BG104151A patent/BG104151A/bg unknown
Non-Patent Citations (1)
| Title |
|---|
| See references of WO9907711A1 * |
Also Published As
| Publication number | Publication date |
|---|---|
| ZA987114B (en) | 2000-02-07 |
| CO4960665A1 (es) | 2000-09-25 |
| NO20000605D0 (no) | 2000-02-07 |
| BR9811091A (pt) | 2000-09-12 |
| TW513435B (en) | 2002-12-11 |
| US6355647B1 (en) | 2002-03-12 |
| SK1052000A3 (en) | 2000-08-14 |
| CA2300391A1 (en) | 1999-02-18 |
| JP2001512734A (ja) | 2001-08-28 |
| AU749539B2 (en) | 2002-06-27 |
| HUP0101311A1 (hu) | 2001-09-28 |
| DE19734444A1 (de) | 1999-02-11 |
| BG104151A (bg) | 2000-10-31 |
| IL134161A0 (en) | 2001-04-30 |
| WO1999007711A1 (de) | 1999-02-18 |
| NZ502657A (en) | 2001-06-29 |
| CN1267303A (zh) | 2000-09-20 |
| AU9068398A (en) | 1999-03-01 |
| CZ2000462A3 (cs) | 2000-05-17 |
| TR200000371T2 (tr) | 2000-11-21 |
| PL340726A1 (en) | 2001-02-26 |
| AR016594A1 (es) | 2001-07-25 |
| ID24222A (id) | 2000-07-13 |
| HUP0101311A3 (en) | 2002-10-28 |
| HRP980435A2 (en) | 1999-04-30 |
| KR20010022658A (ko) | 2001-03-26 |
| CZ290678B6 (cs) | 2002-09-11 |
| NO20000605L (no) | 2000-02-07 |
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