NO333118B1 - 1-fenylalkankarboksylsyrederivater til behandling av nevrodegenerative sykdommer. - Google Patents
1-fenylalkankarboksylsyrederivater til behandling av nevrodegenerative sykdommer. Download PDFInfo
- Publication number
- NO333118B1 NO333118B1 NO20053855A NO20053855A NO333118B1 NO 333118 B1 NO333118 B1 NO 333118B1 NO 20053855 A NO20053855 A NO 20053855A NO 20053855 A NO20053855 A NO 20053855A NO 333118 B1 NO333118 B1 NO 333118B1
- Authority
- NO
- Norway
- Prior art keywords
- chf
- alkyl
- branched
- compound according
- linear
- Prior art date
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- 230000004770 neurodegeneration Effects 0.000 title claims abstract description 7
- 208000015122 neurodegenerative disease Diseases 0.000 title claims abstract description 7
- 239000002253 acid Substances 0.000 title abstract description 5
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 10
- 150000001875 compounds Chemical class 0.000 claims description 44
- 229910052731 fluorine Inorganic materials 0.000 claims description 19
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 17
- 239000011737 fluorine Substances 0.000 claims description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- 229910052799 carbon Inorganic materials 0.000 claims description 12
- 150000001721 carbon Chemical group 0.000 claims description 11
- 239000000203 mixture Substances 0.000 claims description 11
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 10
- 125000000623 heterocyclic group Chemical group 0.000 claims description 10
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 7
- 229940079593 drug Drugs 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 6
- XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 claims description 6
- LIYLTQQDABRNRX-UHFFFAOYSA-N 1-[4-(3,4-dichlorophenyl)-3-fluorophenyl]cyclopropane-1-carboxylic acid Chemical compound C=1C=C(C=2C=C(Cl)C(Cl)=CC=2)C(F)=CC=1C1(C(=O)O)CC1 LIYLTQQDABRNRX-UHFFFAOYSA-N 0.000 claims description 5
- 125000003289 ascorbyl group Chemical group [H]O[C@@]([H])(C([H])([H])O*)[C@@]1([H])OC(=O)C(O*)=C1O* 0.000 claims description 5
- 150000002148 esters Chemical class 0.000 claims description 5
- 230000001225 therapeutic effect Effects 0.000 claims description 5
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
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- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 4
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 4
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- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 4
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- TXCDCPKCNAJMEE-UHFFFAOYSA-N dibenzofuran Chemical compound C1=CC=C2C3=CC=CC=C3OC2=C1 TXCDCPKCNAJMEE-UHFFFAOYSA-N 0.000 claims description 4
- IYYZUPMFVPLQIF-UHFFFAOYSA-N dibenzothiophene Chemical compound C1=CC=C2C3=CC=CC=C3SC2=C1 IYYZUPMFVPLQIF-UHFFFAOYSA-N 0.000 claims description 4
- -1 ethylenedioxy Chemical group 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 4
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
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- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 2
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- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 claims description 2
- ABADUMLIAZCWJD-UHFFFAOYSA-N 1,3-dioxole Chemical compound C1OC=CO1 ABADUMLIAZCWJD-UHFFFAOYSA-N 0.000 claims description 2
- VMLKTERJLVWEJJ-UHFFFAOYSA-N 1,5-naphthyridine Chemical compound C1=CC=NC2=CC=CN=C21 VMLKTERJLVWEJJ-UHFFFAOYSA-N 0.000 claims description 2
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 2
- ODMMNALOCMNQJZ-UHFFFAOYSA-N 1H-pyrrolizine Chemical compound C1=CC=C2CC=CN21 ODMMNALOCMNQJZ-UHFFFAOYSA-N 0.000 claims description 2
- VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 claims description 2
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 claims description 2
- KYNSBQPICQTCGU-UHFFFAOYSA-N Benzopyrane Chemical compound C1=CC=C2C=CCOC2=C1 KYNSBQPICQTCGU-UHFFFAOYSA-N 0.000 claims description 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 2
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- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 2
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 238000000126 in silico method Methods 0.000 claims description 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 2
- 125000004043 oxo group Chemical group O=* 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 claims description 2
- 230000003449 preventive effect Effects 0.000 claims description 2
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 2
- GVIJJXMXTUZIOD-UHFFFAOYSA-N thianthrene Chemical compound C1=CC=C2SC3=CC=CC=C3SC2=C1 GVIJJXMXTUZIOD-UHFFFAOYSA-N 0.000 claims description 2
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- 101000795849 Calliactis parasitica Delta-hormotoxin-Cpt1b Proteins 0.000 claims 1
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- 238000000034 method Methods 0.000 abstract description 13
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C15/00—Cyclic hydrocarbons containing only six-membered aromatic rings as cyclic parts
- C07C15/12—Polycyclic non-condensed hydrocarbons
- C07C15/14—Polycyclic non-condensed hydrocarbons all phenyl groups being directly linked
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/62—Halogen-containing esters
- C07C69/65—Halogen-containing esters of unsaturated acids
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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
-
- 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
- A61P25/28—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/02—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
- C07C233/11—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with carbon atoms of carboxamide groups bound to carbon atoms of an unsaturated carbon skeleton containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
- C07C57/52—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing halogen
- C07C57/58—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing halogen containing six-membered aromatic rings
- C07C57/60—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing halogen containing six-membered aromatic rings having unsaturation outside the rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
- C07C57/52—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing halogen
- C07C57/62—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing halogen containing six-membered aromatic rings and other rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C61/00—Compounds having carboxyl groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C61/16—Unsaturated compounds
- C07C61/40—Unsaturated compounds containing halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Epidemiology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrane Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ITMI20030311 ITMI20030311A1 (it) | 2003-02-21 | 2003-02-21 | Acidi 2-fenil-2-dialchil-acetici per il trattamento della malattia di alzheimer. |
| ITMI20032068 ITMI20032068A1 (it) | 2003-10-23 | 2003-10-23 | Derivati dell'acido 1-fenilcicloalcancarbossilico per il trattamento delle malattie neurodegenerative. |
| PCT/EP2004/001596 WO2004074232A1 (en) | 2003-02-21 | 2004-02-19 | 1-phenylalkanecarboxylic acid derivatives for the treatment of neurodegenerative diseases |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO20053855D0 NO20053855D0 (no) | 2005-08-18 |
| NO20053855L NO20053855L (no) | 2005-11-21 |
| NO333118B1 true NO333118B1 (no) | 2013-03-04 |
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| EP (1) | EP1594833B1 (pt) |
| JP (1) | JP4472691B2 (pt) |
| KR (2) | KR101152448B1 (pt) |
| AT (1) | ATE409176T1 (pt) |
| AU (1) | AU2004213145B2 (pt) |
| BR (1) | BRPI0407662B8 (pt) |
| CA (1) | CA2514384C (pt) |
| CY (1) | CY1108514T1 (pt) |
| DE (1) | DE602004016729D1 (pt) |
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| HK (1) | HK1087398A1 (pt) |
| NO (1) | NO333118B1 (pt) |
| PT (1) | PT1594833E (pt) |
| SI (1) | SI1594833T1 (pt) |
| WO (1) | WO2004074232A1 (pt) |
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| EP1284729A4 (en) * | 2000-04-13 | 2007-12-19 | Mayo Foundation | REDUCTION AGENTS OF A (BETA) 42 |
| EP1603548A4 (en) * | 2003-02-05 | 2007-10-10 | Myriad Genetics Inc | COMPOSITION AND METHOD FOR TREATING NEURODEGENERATIVE DISORDERS |
| ES2312964T3 (es) * | 2003-02-21 | 2009-03-01 | Chiesi Farmaceutici S.P.A. | Derivados de acidos 1-fenilalcanocarboxilicos para el tratamiento de enfermedades neurodegenerativas. |
| EP1651195A4 (en) * | 2003-07-11 | 2007-10-03 | Myriad Genetics Inc | PHARMACEUTICAL PROCESSES, DOSIERSCHEMATA AND DOSAGE FORMS FOR THE TREATMENT OF ALZHEIMER DISEASE |
| US20070293538A1 (en) * | 2004-04-13 | 2007-12-20 | Myriad Genetics, Incorporated | Pharmaceutical Composition And Methods For Treating Neurodegenerative Disorders |
| EP1745180A1 (en) * | 2004-04-29 | 2007-01-24 | Keystone Retaining Wall Systems, Inc. | Veneers for walls, retaining walls and the like |
| DE602005007912D1 (de) | 2004-08-03 | 2008-08-14 | Chiesi Farma Spa | Derivate von 1-phenylalkancarbonsäuren zur behandlung von neurodegenerativen krankheiten |
| CA2618985A1 (en) * | 2004-08-11 | 2006-02-23 | Myriad Genetics, Inc. | Pharmaceutical composition and method for treating neurodegenerative disorders |
| WO2006020850A2 (en) * | 2004-08-11 | 2006-02-23 | Myriad Genetics, Inc. | Pharmaceutical composition and method for treating neurodegenerative disorders |
| WO2006020852A2 (en) * | 2004-08-11 | 2006-02-23 | Myriad Genetics, Inc. | Pharmaceutical composition and method for treating neurodegenerative disorders |
| BRPI0613611A2 (pt) * | 2005-07-22 | 2011-01-18 | Myriad Genetics Inc | formulações de alta concentração de fármaco e formas de dosagens |
| EP2046119A2 (en) * | 2006-07-07 | 2009-04-15 | Myriad Genetics, Inc. | Treatment of psychiatric disorders |
| JO3598B1 (ar) | 2006-10-10 | 2020-07-05 | Infinity Discovery Inc | الاحماض والاسترات البورونية كمثبطات اميد هيدروليز الحامض الدهني |
| CA2710477A1 (en) | 2007-12-20 | 2009-07-09 | Envivo Pharmaceuticals, Inc. | Tetrasubstituted benzenes |
| EP2133322A1 (en) | 2008-06-11 | 2009-12-16 | CHIESI FARMACEUTICI S.p.A. | Process of preparing derivatives of 1-(2-halobiphenyl-4-yl)-cyclopropanecarboxylic acid |
| SG178239A1 (en) * | 2009-08-04 | 2012-03-29 | Chiesi Farma Spa | Process for the preparation of derivatives of 1-(2-halobiphenyl-4-yl)-cyclopropanecarboxylic acid |
| RU2569061C2 (ru) | 2010-02-03 | 2015-11-20 | Инфинити Фармасьютикалз, Инк. | Ингибиторы амид-гидролазы жирных кислот |
| EP2552881A1 (en) * | 2010-04-01 | 2013-02-06 | Chiesi Farmaceutici S.p.A. | Novel polymorphs and salts |
| WO2011131661A1 (en) | 2010-04-21 | 2011-10-27 | Chiesi Farmaceutici S.P.A. | 1-(2-fluorobiphenyl-4-yl)-alkyl carboxylic acid derivatives for the therapy of transthyretin amyloidosis |
| RU2012151850A (ru) | 2010-06-04 | 2014-07-20 | КЬЕЗИ ФАРМАЧЕУТИЧИ С.п.А. | Производные 1-(2-фторбифенил-4-ил)циклопропанкарбоновой кислоты для терапии прионных болезней |
| US9592210B2 (en) | 2011-12-22 | 2017-03-14 | Chiesi Farmaceutici S.P.A. | 1-phenylalkanecarboxylic acid derivatives for the treatment of cognitive impairment |
| US8835494B2 (en) | 2012-04-04 | 2014-09-16 | Chiesi Farmaceutici S.P.A. | Derivatives of 1-(2-halo-biphenyl-4-yl)-Alkanecarboxylic for the treatment of neurodegenerative diseases |
| US8889730B2 (en) | 2012-04-10 | 2014-11-18 | Pfizer Inc. | Indole and indazole compounds that activate AMPK |
| CA2905242C (en) | 2013-03-15 | 2016-11-29 | Pfizer Inc. | Indole compounds that activate ampk |
| EP3013786B1 (en) | 2013-06-24 | 2018-04-04 | Chiesi Farmaceutici S.p.A. | Improved process for the preparation of derivatives of 1-(2-fluoro[1,1'-biphenyl]-4-yl)-cyclopropanecarboxylic acid |
| EP2818460A1 (en) | 2013-06-24 | 2014-12-31 | ZaCh System S.p.A. | Cyclopropanation of substituted phenylacetonitriles or phenyl acetates |
| WO2015109109A1 (en) | 2014-01-15 | 2015-07-23 | Forum Pharmaceuticals Inc. | Fused morpholinopyrimidines and methods of use thereof |
| US20150320706A1 (en) | 2014-05-12 | 2015-11-12 | Chiesi Farmaceutici S.P.A. | Formulations and methods of treating alzheimer's disease and other proteinopathies by combination therapy |
| US20150335596A1 (en) | 2014-05-26 | 2015-11-26 | Chiesi Farmaceutici S.P.A. | 1-(2-fluorobiphenyl-4-yl)-cyclopropanecarboxylic acid derivatives for the treatment of down's syndrome |
| US9802927B2 (en) | 2015-06-10 | 2017-10-31 | Denali Therapeutics, Inc. | Oxadiazine compounds and methods of use thereof |
| CN117897174A (zh) | 2021-08-31 | 2024-04-16 | 塞雷斯皮尔股份有限公司 | 共晶 |
Family Cites Families (12)
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| BE735385A (pt) * | 1968-07-04 | 1969-12-01 | ||
| JPS4994680A (pt) | 1973-01-22 | 1974-09-09 | ||
| JPS5046669A (pt) | 1973-03-28 | 1975-04-25 | ||
| JPS58177977A (ja) | 1982-04-09 | 1983-10-18 | Grelan Pharmaceut Co Ltd | ４−フエニルピラゾ−ル類 |
| AU2936295A (en) * | 1994-07-13 | 1996-02-16 | Taisho Pharmaceutical Co., Ltd. | Thiopheneacetic acid derivative |
| JPH0994680A (ja) * | 1995-07-24 | 1997-04-08 | Toyota Motor Corp | 摩擦圧接装置 |
| US5994379A (en) | 1998-02-13 | 1999-11-30 | Merck Frosst Canada, Inc. | Bisaryl COX-2 inhibiting compounds, compositions and methods of use |
| EP1284729A4 (en) | 2000-04-13 | 2007-12-19 | Mayo Foundation | REDUCTION AGENTS OF A (BETA) 42 |
| EP1587798A4 (en) * | 2003-01-14 | 2007-06-27 | Merck & Co Inc | NSAID DERIVATIVES WITH GEMINAL DISUBSTITUTION AS ABETA REDUCING AGENTS 42 |
| ES2312964T3 (es) * | 2003-02-21 | 2009-03-01 | Chiesi Farmaceutici S.P.A. | Derivados de acidos 1-fenilalcanocarboxilicos para el tratamiento de enfermedades neurodegenerativas. |
| DE602005007912D1 (de) * | 2004-08-03 | 2008-08-14 | Chiesi Farma Spa | Derivate von 1-phenylalkancarbonsäuren zur behandlung von neurodegenerativen krankheiten |
| EP2133322A1 (en) * | 2008-06-11 | 2009-12-16 | CHIESI FARMACEUTICI S.p.A. | Process of preparing derivatives of 1-(2-halobiphenyl-4-yl)-cyclopropanecarboxylic acid |
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2004
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- 2004-02-19 CA CA2514384A patent/CA2514384C/en not_active Expired - Fee Related
- 2004-02-19 BR BRPI0407662A patent/BRPI0407662B8/pt not_active IP Right Cessation
- 2004-02-19 SI SI200430900T patent/SI1594833T1/sl unknown
- 2004-02-19 AT AT04712483T patent/ATE409176T1/de active
- 2004-02-19 JP JP2006501896A patent/JP4472691B2/ja not_active Expired - Lifetime
- 2004-02-19 EP EP04712483A patent/EP1594833B1/en not_active Expired - Lifetime
- 2004-02-19 DE DE602004016729T patent/DE602004016729D1/de not_active Expired - Lifetime
- 2004-02-19 PT PT04712483T patent/PT1594833E/pt unknown
- 2004-02-19 KR KR1020117008239A patent/KR101152448B1/ko active IP Right Grant
- 2004-02-19 DK DK04712483T patent/DK1594833T3/da active
- 2004-02-19 US US10/546,190 patent/US7662995B2/en active Active
- 2004-02-19 AU AU2004213145A patent/AU2004213145B2/en not_active Ceased
- 2004-02-19 KR KR1020057014850A patent/KR101088272B1/ko active IP Right Grant
- 2004-02-19 WO PCT/EP2004/001596 patent/WO2004074232A1/en active IP Right Grant
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2005
- 2005-08-18 NO NO20053855A patent/NO333118B1/no not_active IP Right Cessation
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2006
- 2006-07-07 HK HK06107643.0A patent/HK1087398A1/xx not_active IP Right Cessation
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- 2008-11-14 CY CY20081101310T patent/CY1108514T1/el unknown
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- 2009-12-24 US US12/647,069 patent/US8022250B2/en not_active Expired - Lifetime
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