AU2002215159A1 - Combination of GABA agonists and sorbitol dehydrogenase inhibitors - Google Patents
Combination of GABA agonists and sorbitol dehydrogenase inhibitorsInfo
- Publication number
- AU2002215159A1 AU2002215159A1 AU2002215159A AU1515902A AU2002215159A1 AU 2002215159 A1 AU2002215159 A1 AU 2002215159A1 AU 2002215159 A AU2002215159 A AU 2002215159A AU 1515902 A AU1515902 A AU 1515902A AU 2002215159 A1 AU2002215159 A1 AU 2002215159A1
- Authority
- AU
- Australia
- Prior art keywords
- alkyl
- pyrimidin
- optionally substituted
- piperazin
- hydroxy
- 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.)
- Abandoned
Links
- 239000003477 4 aminobutyric acid receptor stimulating agent Substances 0.000 title claims description 69
- 108010009384 L-Iditol 2-Dehydrogenase Proteins 0.000 title description 4
- 102100026974 Sorbitol dehydrogenase Human genes 0.000 title description 4
- 239000003112 inhibitor Substances 0.000 title description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 259
- -1 vinylenylcarbonyl Chemical group 0.000 claims description 168
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 161
- 125000001153 fluoro group Chemical group F* 0.000 claims description 137
- 229940002612 prodrug Drugs 0.000 claims description 99
- 239000000651 prodrug Substances 0.000 claims description 99
- 229910052739 hydrogen Inorganic materials 0.000 claims description 94
- 239000001257 hydrogen Substances 0.000 claims description 94
- 125000003545 alkoxy group Chemical group 0.000 claims description 71
- 150000003839 salts Chemical class 0.000 claims description 65
- 150000001875 compounds Chemical class 0.000 claims description 55
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 52
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 48
- 239000008194 pharmaceutical composition Substances 0.000 claims description 46
- 125000005843 halogen group Chemical group 0.000 claims description 42
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 34
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 33
- UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 claims description 33
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 32
- 125000001424 substituent group Chemical group 0.000 claims description 30
- 125000004076 pyridyl group Chemical group 0.000 claims description 28
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 20
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 18
- 125000005466 alkylenyl group Chemical group 0.000 claims description 17
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 16
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 16
- 125000002541 furyl group Chemical group 0.000 claims description 16
- 125000002757 morpholinyl group Chemical group 0.000 claims description 16
- 125000002971 oxazolyl group Chemical group 0.000 claims description 16
- 125000004193 piperazinyl group Chemical group 0.000 claims description 16
- 125000003386 piperidinyl group Chemical group 0.000 claims description 16
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 16
- 229920006395 saturated elastomer Polymers 0.000 claims description 16
- 125000000335 thiazolyl group Chemical group 0.000 claims description 16
- 125000001544 thienyl group Chemical group 0.000 claims description 16
- 125000002947 alkylene group Chemical group 0.000 claims description 15
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 14
- 229960002870 gabapentin Drugs 0.000 claims description 14
- ZJQHPWUVQPJPQT-UHFFFAOYSA-N muscimol Chemical group NCC1=CC(=O)NO1 ZJQHPWUVQPJPQT-UHFFFAOYSA-N 0.000 claims description 14
- 229910052757 nitrogen Chemical group 0.000 claims description 14
- AYXYPKUFHZROOJ-ZETCQYMHSA-N pregabalin Chemical compound CC(C)C[C@H](CN)CC(O)=O AYXYPKUFHZROOJ-ZETCQYMHSA-N 0.000 claims description 14
- 229960001233 pregabalin Drugs 0.000 claims description 14
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 12
- CXOFVDLJLONNDW-UHFFFAOYSA-N Phenytoin Chemical compound N1C(=O)NC(=O)C1(C=1C=CC=CC=1)C1=CC=CC=C1 CXOFVDLJLONNDW-UHFFFAOYSA-N 0.000 claims description 12
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 12
- KJADKKWYZYXHBB-XBWDGYHZSA-N Topiramic acid Chemical compound C1O[C@@]2(COS(N)(=O)=O)OC(C)(C)O[C@H]2[C@@H]2OC(C)(C)O[C@@H]21 KJADKKWYZYXHBB-XBWDGYHZSA-N 0.000 claims description 12
- PYZRQGJRPPTADH-UHFFFAOYSA-N lamotrigine Chemical compound NC1=NC(N)=NN=C1C1=CC=CC(Cl)=C1Cl PYZRQGJRPPTADH-UHFFFAOYSA-N 0.000 claims description 12
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 claims description 12
- PBJUNZJWGZTSKL-MRXNPFEDSA-N tiagabine Chemical compound C1=CSC(C(=CCCN2C[C@@H](CCC2)C(O)=O)C2=C(C=CS2)C)=C1C PBJUNZJWGZTSKL-MRXNPFEDSA-N 0.000 claims description 12
- 241000124008 Mammalia Species 0.000 claims description 10
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 10
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 10
- 150000002431 hydrogen Chemical group 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 125000001624 naphthyl group Chemical group 0.000 claims description 10
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- 208000002249 Diabetes Complications Diseases 0.000 claims description 9
- 206010012655 Diabetic complications Diseases 0.000 claims description 9
- 239000003085 diluting agent Substances 0.000 claims description 9
- 229960001848 lamotrigine Drugs 0.000 claims description 9
- 229960002036 phenytoin Drugs 0.000 claims description 9
- 229960001918 tiagabine Drugs 0.000 claims description 9
- 229960004394 topiramate Drugs 0.000 claims description 9
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 8
- 125000002785 azepinyl group Chemical group 0.000 claims description 8
- 125000002393 azetidinyl group Chemical group 0.000 claims description 8
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 8
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 8
- 229960000623 carbamazepine Drugs 0.000 claims description 8
- FFGPTBGBLSHEPO-UHFFFAOYSA-N carbamazepine Chemical compound C1=CC2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 FFGPTBGBLSHEPO-UHFFFAOYSA-N 0.000 claims description 8
- 125000002883 imidazolyl group Chemical group 0.000 claims description 8
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 8
- 229910052760 oxygen Inorganic materials 0.000 claims description 8
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 8
- 125000005493 quinolyl group Chemical group 0.000 claims description 8
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 8
- 239000011593 sulfur Chemical group 0.000 claims description 8
- PJDFLNIOAUIZSL-UHFFFAOYSA-N vigabatrin Chemical compound C=CC(N)CCC(O)=O PJDFLNIOAUIZSL-UHFFFAOYSA-N 0.000 claims description 8
- KPYSYYIEGFHWSV-UHFFFAOYSA-N Baclofen Chemical compound OC(=O)CC(CN)C1=CC=C(Cl)C=C1 KPYSYYIEGFHWSV-UHFFFAOYSA-N 0.000 claims description 7
- 229960000794 baclofen Drugs 0.000 claims description 7
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 7
- 229960002752 progabide Drugs 0.000 claims description 7
- IBALRBWGSVJPAP-HEHNFIMWSA-N progabide Chemical compound C=1C(F)=CC=C(O)C=1C(=N/CCCC(=O)N)/C1=CC=C(Cl)C=C1 IBALRBWGSVJPAP-HEHNFIMWSA-N 0.000 claims description 7
- 229960005318 vigabatrin Drugs 0.000 claims description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
- 125000002619 bicyclic group Chemical group 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 6
- 239000001301 oxygen Substances 0.000 claims description 6
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 6
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 6
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 6
- 150000003254 radicals Chemical group 0.000 claims description 6
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 6
- 125000001425 triazolyl group Chemical group 0.000 claims description 6
- FTALBRSUTCGOEG-UHFFFAOYSA-N Riluzole Chemical compound C1=C(OC(F)(F)F)C=C2SC(N)=NC2=C1 FTALBRSUTCGOEG-UHFFFAOYSA-N 0.000 claims description 5
- NIJJYAXOARWZEE-UHFFFAOYSA-N di-n-propyl-acetic acid Natural products CCCC(C(O)=O)CCC NIJJYAXOARWZEE-UHFFFAOYSA-N 0.000 claims description 5
- 229960004181 riluzole Drugs 0.000 claims description 5
- MSRILKIQRXUYCT-UHFFFAOYSA-M valproate semisodium Chemical compound [Na+].CCCC(C(O)=O)CCC.CCCC(C([O-])=O)CCC MSRILKIQRXUYCT-UHFFFAOYSA-M 0.000 claims description 5
- 229960000604 valproic acid Drugs 0.000 claims description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- 125000005090 alkenylcarbonyl group Chemical group 0.000 claims description 4
- 125000003282 alkyl amino group Chemical group 0.000 claims description 4
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 4
- 125000005153 alkyl sulfamoyl group Chemical group 0.000 claims description 4
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 4
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 4
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 4
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 4
- 125000001041 indolyl group Chemical group 0.000 claims description 4
- 125000002950 monocyclic group Chemical group 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 125000004043 oxo group Chemical group O=* 0.000 claims description 4
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 4
- 125000005554 pyridyloxy group Chemical group 0.000 claims description 4
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 4
- 125000004588 thienopyridyl group Chemical group S1C(=CC2=C1C=CC=N2)* 0.000 claims description 4
- 125000004306 triazinyl group Chemical group 0.000 claims description 4
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 3
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 3
- CSDSSGBPEUDDEE-UHFFFAOYSA-N 2-formylpyridine Chemical compound O=CC1=CC=CC=N1 CSDSSGBPEUDDEE-UHFFFAOYSA-N 0.000 claims description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 2
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 claims description 2
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 claims description 2
- 239000004305 biphenyl Substances 0.000 claims description 2
- 235000010290 biphenyl Nutrition 0.000 claims description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 claims description 2
- NLUNLVTVUDIHFE-UHFFFAOYSA-N cyclooctylcyclooctane Chemical group C1CCCCCCC1C1CCCCCCC1 NLUNLVTVUDIHFE-UHFFFAOYSA-N 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 2
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 2
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
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- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 13
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Classifications
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- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
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- 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
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- 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
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/12—Ophthalmic agents for cataracts
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Ophthalmology & Optometry (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Vascular Medicine (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Endocrinology (AREA)
- Dermatology (AREA)
- Emergency Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US25006900P | 2000-11-30 | 2000-11-30 | |
| US60/250,069 | 2000-11-30 | ||
| PCT/IB2001/002213 WO2002043762A2 (en) | 2000-11-30 | 2001-11-19 | Combination of gaba agonists and sorbitol dehydrogenase inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2002215159A1 true AU2002215159A1 (en) | 2002-06-11 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2002215159A Abandoned AU2002215159A1 (en) | 2000-11-30 | 2001-11-19 | Combination of GABA agonists and sorbitol dehydrogenase inhibitors |
Country Status (38)
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| US (1) | US6544998B2 (cs) |
| EP (1) | EP1337271B1 (cs) |
| JP (1) | JP2004514699A (cs) |
| KR (1) | KR20030059290A (cs) |
| CN (1) | CN1477975A (cs) |
| AP (1) | AP2001002360A0 (cs) |
| AR (1) | AR031431A1 (cs) |
| AT (1) | ATE281181T1 (cs) |
| AU (1) | AU2002215159A1 (cs) |
| BG (1) | BG107774A (cs) |
| BR (1) | BR0115783A (cs) |
| CA (1) | CA2430298A1 (cs) |
| CR (1) | CR6964A (cs) |
| CZ (1) | CZ20031399A3 (cs) |
| DE (1) | DE60106968T2 (cs) |
| DO (1) | DOP2001000289A (cs) |
| EA (1) | EA200300432A1 (cs) |
| EC (1) | ECSP034624A (cs) |
| EE (1) | EE200300248A (cs) |
| ES (1) | ES2230378T3 (cs) |
| HR (1) | HRP20030420A2 (cs) |
| HU (1) | HUP0302160A3 (cs) |
| IL (1) | IL155704A0 (cs) |
| IS (1) | IS6786A (cs) |
| MA (1) | MA26964A1 (cs) |
| MX (1) | MXPA03004870A (cs) |
| NO (1) | NO20032441L (cs) |
| OA (1) | OA12534A (cs) |
| PA (1) | PA8534101A1 (cs) |
| PE (1) | PE20020597A1 (cs) |
| PL (1) | PL365927A1 (cs) |
| PT (1) | PT1337271E (cs) |
| SK (1) | SK6192003A3 (cs) |
| SV (1) | SV2003000751A (cs) |
| TN (1) | TNSN01169A1 (cs) |
| UY (1) | UY27042A1 (cs) |
| WO (1) | WO2002043762A2 (cs) |
| ZA (1) | ZA200303381B (cs) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100491282B1 (ko) | 1996-07-24 | 2005-05-24 | 워너-램버트 캄파니 엘엘씨 | 통증 치료용 이소부틸가바 및 그의 유도체 |
| US6992109B1 (en) * | 1999-04-08 | 2006-01-31 | Segal Catherine A | Method for the treatment of incontinence |
| US7022678B2 (en) * | 2001-03-30 | 2006-04-04 | Warner-Lambert Company | Pregabalin lactose conjugates |
| SK286227B6 (sk) * | 2001-05-25 | 2008-05-06 | Warner-Lambert Company Llc | Kvapalná farmaceutická kompozícia obsahujúca analóg GABA a spôsob jej prípravy a použitie |
| CA2451267A1 (en) * | 2002-12-13 | 2004-06-13 | Warner-Lambert Company Llc | Pharmaceutical uses for alpha2delta ligands |
| KR20050036195A (ko) * | 2003-10-15 | 2005-04-20 | 고재영 | 신규한 망막병증 치료제 조성물 |
| US8007827B2 (en) * | 2004-04-02 | 2011-08-30 | Impax Laboratories, Inc. | Pharmaceutical dosage forms having immediate release and/or controlled release properties |
| CA2560995A1 (en) * | 2004-04-02 | 2005-10-20 | Impax Laboratories, Inc. | Controlled release dosage for gaba receptor agonist |
| US20050220873A1 (en) * | 2004-04-02 | 2005-10-06 | Chien-Hsuan Han | Pharmaceutical dosage forms having immediate and controlled release properties that contain a GABAB receptor agonist |
| US20050226927A1 (en) * | 2004-04-02 | 2005-10-13 | Impax Laboratories, Inc. | Pharmaceutical dosage forms having immediate release and/or controlled release properties that contain a GABAB receptor agonist |
| GB0420831D0 (en) | 2004-09-17 | 2004-10-20 | Glaxo Group Ltd | Novel compounds |
| ES2528674T3 (es) | 2005-02-17 | 2015-02-11 | Astellas Pharma Inc. | Piperidina y carboxilatos de piperacina como inhibidores de FAAH |
| GB0513553D0 (en) * | 2005-07-01 | 2005-08-10 | Fond D Amico Per La Ricerca Su | Rab3a |
| DK2142529T3 (da) | 2007-04-27 | 2014-02-10 | Purdue Pharma Lp | Trpv1-antagonister og anvendelser deraf |
| JP5452494B2 (ja) * | 2007-10-09 | 2014-03-26 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | ベンフォチアミンと１または２種以上の医薬活性剤とを含む神経因性の疼痛状態の処置のための医薬組成物 |
| SG176464A1 (en) | 2008-05-09 | 2011-12-29 | Agency Science Tech & Res | Diagnosis and treatment of kawasaki disease |
| JP5815552B2 (ja) | 2009-12-08 | 2015-11-17 | ケース ウェスタン リザーブ ユニバーシティＣａｓｅ Ｗｅｓｔｅｒｎｒｅｓｅｒｖｅ Ｕｎｉｖｅｒｓｉｔｙ | 眼疾患を治療する化合物および方法 |
| DK2621282T3 (da) * | 2010-09-28 | 2020-05-04 | Univ California | Gaba-agonister i behandlingen af forstyrrelser forbundet med metabolisk syndrom og gaba-kombinationer i behandling eller profylakse af type i diabetes |
| CA2837178C (en) | 2011-06-22 | 2016-09-20 | Purdue Pharma L.P. | Trpv1 antagonists including dihydroxy substituent and uses thereof |
| US8652527B1 (en) | 2013-03-13 | 2014-02-18 | Upsher-Smith Laboratories, Inc | Extended-release topiramate capsules |
| US9101545B2 (en) | 2013-03-15 | 2015-08-11 | Upsher-Smith Laboratories, Inc. | Extended-release topiramate capsules |
| GB2571696B (en) | 2017-10-09 | 2020-05-27 | Compass Pathways Ltd | Large scale method for the preparation of Psilocybin and formulations of Psilocybin so produced |
| EP3955936A1 (en) | 2019-04-17 | 2022-02-23 | COMPASS Pathfinder Limited | Treatment of depression and other various disorders with psilocybin |
| JP2022531466A (ja) * | 2019-05-07 | 2022-07-06 | ユニバーシティ オブ マイアミ | 遺伝性ニューロパチーおよび関連障害の処置および検出 |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2409754A (en) | 1946-10-22 | Method for obtaining hydantoins | ||
| CH449645A (de) | 1963-07-09 | 1968-01-15 | Ciba Geigy | Verfahren zur Herstellung neuer Aminosäuren |
| CH427803A (de) | 1963-12-06 | 1967-01-15 | Geigy Ag J R | Verfahren zur Herstellung eines neuen Isoxazolderivates |
| DE2460891C2 (de) * | 1974-12-21 | 1982-09-23 | Gödecke AG, 1000 Berlin | 1-Aminomethyl-1-cycloalkanessigsäuren und deren Ester, Verfahren zu deren Herstellung und diese Verbindungen enthaltende Arzneimittel |
| US3960927A (en) | 1975-03-18 | 1976-06-01 | Richardson-Merrell Inc. | Olefinic derivatives of amino acids |
| FR2319338A1 (fr) * | 1975-08-01 | 1977-02-25 | Synthelabo | Nouveaux derives de a- phenyl benzylideniques des acides amines, leur preparation et les medicaments qui en contiennent |
| DK153787C (da) | 1979-06-01 | 1989-01-16 | Wellcome Found | Analogifremgangsmaade til fremstilling af substituerede 3,5-diamino-6-phenyl-1,2,4-triaziner og alfa-cyanobenzyliden-aminoguanidinforbindelser til anvendelse som mellemprodukter herved |
| FR2492258A1 (fr) * | 1980-10-17 | 1982-04-23 | Pharmindustrie | Nouveau medicament a base d'amino-2 trifluoromethoxy-6 benzothiazole |
| US4513006A (en) | 1983-09-26 | 1985-04-23 | Mcneil Lab., Inc. | Anticonvulsant sulfamate derivatives |
| DK288385D0 (da) | 1985-06-26 | 1985-06-26 | Novo Industri As | Aminosyrederivater |
| US6197819B1 (en) | 1990-11-27 | 2001-03-06 | Northwestern University | Gamma amino butyric acid analogs and optical isomers |
| KR950703539A (ko) * | 1992-09-28 | 1995-09-20 | 알렌 제이. 스피겔 | 당뇨병 합병증 치료용 치환된 피리미딘(substituted pyrimidines for control or diabetic complications) |
| AU3503300A (en) * | 1999-02-24 | 2000-09-14 | Regents Of The University Of California, The | Gaba receptors mediate inhibition of t cell responses |
| DE60009777T2 (de) * | 1999-04-01 | 2004-08-19 | Pfizer Products Inc., Groton | Verbindung für Behandlung und Vorsorge bei Diabetes |
| EP1185275A1 (en) * | 1999-04-01 | 2002-03-13 | Pfizer Products Inc. | Aminopyrimidines as sorbitol dehydrogenase inhibitors |
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