JP2008504274A - アミド化合物およびその医薬としての使用 - Google Patents
アミド化合物およびその医薬としての使用 Download PDFInfo
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- JP2008504274A JP2008504274A JP2007518256A JP2007518256A JP2008504274A JP 2008504274 A JP2008504274 A JP 2008504274A JP 2007518256 A JP2007518256 A JP 2007518256A JP 2007518256 A JP2007518256 A JP 2007518256A JP 2008504274 A JP2008504274 A JP 2008504274A
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- Prior art keywords
- aryl
- alkyl
- cycloalkyl
- heteroaryl
- haloalkyl
- Prior art date
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- 125000000217 alkyl group Chemical group 0.000 claims description 183
- 125000001072 heteroaryl group Chemical group 0.000 claims description 179
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 128
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- 125000005843 halogen group Chemical group 0.000 claims description 83
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 77
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 77
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 77
- 125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims description 76
- 238000000034 method Methods 0.000 claims description 68
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 53
- 229910052799 carbon Inorganic materials 0.000 claims description 48
- 229910052739 hydrogen Inorganic materials 0.000 claims description 47
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- 125000003545 alkoxy group Chemical group 0.000 claims description 36
- 125000004429 atom Chemical group 0.000 claims description 35
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- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 24
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- YVYUWSZAJHKIGM-UHFFFAOYSA-N 1,3,3a,4,5,9b-hexahydrobenzo[e]isoindol-2-yl-[1-(benzenesulfonyl)piperidin-3-yl]methanone Chemical compound C1C2CCC3=CC=CC=C3C2CN1C(=O)C(C1)CCCN1S(=O)(=O)C1=CC=CC=C1 YVYUWSZAJHKIGM-UHFFFAOYSA-N 0.000 claims description 2
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- JUPAKBAVGWUQPS-GNZRSQJKSA-N 3,4,4a,5,6,7,8,8a-octahydro-2h-quinolin-1-yl-[(3s)-1-(3-bromophenyl)sulfonylpiperidin-3-yl]methanone Chemical compound BrC1=CC=CC(S(=O)(=O)N2C[C@H](CCC2)C(=O)N2C3CCCCC3CCC2)=C1 JUPAKBAVGWUQPS-GNZRSQJKSA-N 0.000 claims description 2
- AHXMVKYKVRBJSO-FDYSRKEFSA-N 3,4,4a,5,6,7,8,8a-octahydro-2h-quinolin-1-yl-[(3s)-1-(3-chloro-2-methylphenyl)sulfonylpiperidin-3-yl]methanone Chemical compound CC1=C(Cl)C=CC=C1S(=O)(=O)N1C[C@@H](C(=O)N2C3CCCCC3CCC2)CCC1 AHXMVKYKVRBJSO-FDYSRKEFSA-N 0.000 claims description 2
- PXUURYWUNSXDKI-QGZVFWFLSA-N 3,4-dihydro-2h-quinolin-1-yl-[(3r)-1-(2-nitrophenyl)sulfonylpiperidin-3-yl]methanone Chemical compound [O-][N+](=O)C1=CC=CC=C1S(=O)(=O)N1C[C@H](C(=O)N2C3=CC=CC=C3CCC2)CCC1 PXUURYWUNSXDKI-QGZVFWFLSA-N 0.000 claims description 2
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- DQICGTZZGCTBOK-KSZLIROESA-N [(3ar,7as)-1,3,3a,4,5,6,7,7a-octahydroisoindol-2-yl]-[(3s)-1-(3-chloro-2-methylphenyl)sulfonylpiperidin-3-yl]methanone Chemical compound CC1=C(Cl)C=CC=C1S(=O)(=O)N1C[C@@H](C(=O)N2C[C@@H]3CCCC[C@@H]3C2)CCC1 DQICGTZZGCTBOK-KSZLIROESA-N 0.000 claims description 2
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- ZKOOSEKUIZQMKP-GOSISDBHSA-N [(3r)-1-(benzenesulfonyl)piperidin-3-yl]-(3,4-dihydro-2h-quinolin-1-yl)methanone Chemical compound C([C@H](C1)C(=O)N2C3=CC=CC=C3CCC2)CCN1S(=O)(=O)C1=CC=CC=C1 ZKOOSEKUIZQMKP-GOSISDBHSA-N 0.000 claims description 2
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- XOZBTMPFBWBSMA-MOPGFXCFSA-N [(3s)-1-(3-chloro-2-methylphenyl)sulfonylpiperidin-3-yl]-[(3s)-3-pyridin-3-ylpyrrolidin-1-yl]methanone Chemical compound CC1=C(Cl)C=CC=C1S(=O)(=O)N1C[C@@H](C(=O)N2C[C@@H](CC2)C=2C=NC=CC=2)CCC1 XOZBTMPFBWBSMA-MOPGFXCFSA-N 0.000 claims description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
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- 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
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
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- 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
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
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- A—HUMAN NECESSITIES
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- 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
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
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- A—HUMAN NECESSITIES
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- 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
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/92—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with a hetero atom directly attached to the ring nitrogen atom
- C07D211/96—Sulfur atom
-
- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
-
- 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
- C07D401/14—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 three or more hetero rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Rheumatology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Physical Education & Sports Medicine (AREA)
- Urology & Nephrology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Emergency Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Pain & Pain Management (AREA)
- Endocrinology (AREA)
- Psychiatry (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Hydrogenated Pyridines (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US58247804P | 2004-06-24 | 2004-06-24 | |
| PCT/US2005/022170 WO2006012173A1 (en) | 2004-06-24 | 2005-06-23 | Amido compounds and their use as pharmaceuticals |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2008504274A true JP2008504274A (ja) | 2008-02-14 |
| JP2008504274A5 JP2008504274A5 (OSRAM) | 2008-08-07 |
Family
ID=35786518
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007518256A Withdrawn JP2008504274A (ja) | 2004-06-24 | 2005-06-23 | アミド化合物およびその医薬としての使用 |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US20050288317A1 (OSRAM) |
| EP (1) | EP1758882A4 (OSRAM) |
| JP (1) | JP2008504274A (OSRAM) |
| CN (1) | CN101001850A (OSRAM) |
| AU (1) | AU2005267331A1 (OSRAM) |
| BR (1) | BRPI0512630A (OSRAM) |
| CA (1) | CA2569507A1 (OSRAM) |
| MX (1) | MXPA06014573A (OSRAM) |
| WO (1) | WO2006012173A1 (OSRAM) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008531616A (ja) * | 2005-03-03 | 2008-08-14 | エフ．ホフマン−ラ ロシュ アーゲー | ＩＩ型糖尿病の処置用の１１−β−ヒドロキシステロイド・デヒドロゲナーゼのインヒビターとしての１−スルホニル−ピペリジン−３−カルボン酸アミド誘導体 |
| JP2010535834A (ja) * | 2007-08-13 | 2010-11-25 | エフ．ホフマン−ラ ロシュ アーゲー | 新規ピペラジンアミド誘導体 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7880001B2 (en) | 2004-04-29 | 2011-02-01 | Abbott Laboratories | Inhibitors of the 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme |
| US20100222316A1 (en) | 2004-04-29 | 2010-09-02 | Abbott Laboratories | Inhibitors of the 11-beta-hydroxysteroid dehydrogenase type 1 enzyme |
| US8415354B2 (en) | 2004-04-29 | 2013-04-09 | Abbott Laboratories | Methods of use of inhibitors of the 11-beta-hydroxysteroid dehydrogenase type 1 enzyme |
| TWI350168B (en) | 2004-05-07 | 2011-10-11 | Incyte Corp | Amido compounds and their use as pharmaceuticals |
| JP2008504280A (ja) * | 2004-06-24 | 2008-02-14 | インサイト・コーポレイション | ２−メチルプロパンアミドおよびその医薬としての使用 |
| JP2008504279A (ja) * | 2004-06-24 | 2008-02-14 | インサイト・コーポレイション | アミド化合物およびその医薬としての使用 |
| WO2006002349A1 (en) * | 2004-06-24 | 2006-01-05 | Incyte Corporation | Amido compounds and their use as pharmaceuticals |
| CA2570694A1 (en) * | 2004-06-24 | 2006-02-02 | Incyte Corporation | Amido compounds and their use as pharmaceuticals |
| EP1758580A4 (en) | 2004-06-24 | 2008-01-16 | Incyte Corp | N-SUBSTITUTED PIPERIDINE AND ITS USE AS A MEDICAMENT |
| MX2007001540A (es) * | 2004-08-10 | 2007-04-23 | Incyte Corp | Compuestos amido y sus usos como farmaceuticos. |
| US8110581B2 (en) | 2004-11-10 | 2012-02-07 | Incyte Corporation | Lactam compounds and their use as pharmaceuticals |
| US20060116382A1 (en) * | 2004-11-10 | 2006-06-01 | Wenqing Yao | Lactam compounds and their use as pharmaceuticals |
| KR20070097441A (ko) * | 2004-11-18 | 2007-10-04 | 인사이트 산 디에고 인코포레이티드 | 11-β 하이드록실 스테로이드 데하이드로게나제 유형 1의억제제 및 이를 사용하는 방법 |
| EP1846362A2 (en) | 2005-01-05 | 2007-10-24 | Abbott Laboratories | Inhibitors of the 11-beta-hydroxysteroid dehydrogenase type 1 enzyme |
| US20090192198A1 (en) | 2005-01-05 | 2009-07-30 | Abbott Laboratories | Inhibitors of the 11-beta-hydroxysteroid dehydrogenase type 1 enzyme |
| US8198331B2 (en) | 2005-01-05 | 2012-06-12 | Abbott Laboratories | Inhibitors of the 11-beta-hydroxysteroid dehydrogenase type 1 enzyme |
| KR101496206B1 (ko) | 2005-01-05 | 2015-02-27 | 애브비 인코포레이티드 | 11-베타-하이드록시스테로이드 데하이드로게나제 타입 1 효소의 억제제로서의 아다만틸 유도체 |
| US7759339B2 (en) * | 2005-03-31 | 2010-07-20 | Takeda San Diego, Inc. | Hydroxysteroid dehydrogenase inhibitors |
| MY144968A (en) | 2005-04-11 | 2011-11-30 | Xenon Pharmaceuticals Inc | Spiro-oxindole compounds and their uses as therapeutic agents |
| AR053710A1 (es) | 2005-04-11 | 2007-05-16 | Xenon Pharmaceuticals Inc | Compuestos espiroheterociclicos y sus usos como agentes terapeuticos |
| US20060235028A1 (en) * | 2005-04-14 | 2006-10-19 | Li James J | Inhibitors of 11-beta hydroxysteroid dehydrogenase type I |
| EP1931652A2 (en) * | 2005-09-21 | 2008-06-18 | Incyte Corporation | Amido compounds and their use as pharmaceuticals |
| TW200804382A (en) | 2005-12-05 | 2008-01-16 | Incyte Corp | Lactam compounds and methods of using the same |
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| BRPI0715160A2 (pt) | 2006-08-08 | 2013-06-11 | Sanofi Aventis | imidazolidina-2,4-dionas substituÍdas por arilamimoaril-alquil-, processo para preparÁ-las, medicamentos compeendendo estes compostos, e seu uso |
| MX2009003876A (es) | 2006-10-12 | 2009-05-11 | Xenon Pharmaceuticals Inc | Uso de compuestos de espiro-oxindol como agentes terapeuticos. |
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| ES2375586T3 (es) * | 2007-03-30 | 2012-03-02 | F. Hoffmann-La Roche Ag | Derivados de imidazolidinona. |
| CL2008001839A1 (es) | 2007-06-21 | 2009-01-16 | Incyte Holdings Corp | Compuestos derivados de 2,7-diazaespirociclos, inhibidores de 11-beta hidroxil esteroide deshidrogenasa tipo 1; composicion farmaceutica que comprende a dichos compuestos; utiles para tratar la obesidad, diabetes, intolerancia a la glucosa, diabetes tipo ii, entre otras enfermedades. |
| EP2025674A1 (de) | 2007-08-15 | 2009-02-18 | sanofi-aventis | Substituierte Tetrahydronaphthaline, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| JP5736098B2 (ja) | 2007-08-21 | 2015-06-17 | アッヴィ・インコーポレイテッド | 中枢神経系障害を治療するための医薬組成物 |
| MX2010007968A (es) * | 2008-02-12 | 2010-08-04 | Hoffmann La Roche | Derivados de sulfonamida piperidina. |
| WO2010003624A2 (en) | 2008-07-09 | 2010-01-14 | Sanofi-Aventis | Heterocyclic compounds, processes for their preparation, medicaments comprising these compounds, and the use thereof |
| PT2350090E (pt) | 2008-10-17 | 2015-11-13 | Xenon Pharmaceuticals Inc | Composto espiro-oxindol e suas utilizações como agentes terapêuticos |
| WO2010045197A1 (en) | 2008-10-17 | 2010-04-22 | Xenon Pharmaceuticals, Inc. | Spiro-oxindole compounds and their use as therapeutic agents |
| WO2010068601A1 (en) | 2008-12-08 | 2010-06-17 | Sanofi-Aventis | A crystalline heteroaromatic fluoroglycoside hydrate, processes for making, methods of use and pharmaceutical compositions thereof |
| ES2350077B1 (es) | 2009-06-04 | 2011-11-04 | Laboratorios Salvat, S.A. | Compuestos inhibidores de 11beta-hidroxiesteroide deshidrogenasa de tipo 1. |
| AR077252A1 (es) | 2009-06-29 | 2011-08-10 | Xenon Pharmaceuticals Inc | Enantiomeros de compuestos de espirooxindol y sus usos como agentes terapeuticos |
| ES2443016T3 (es) | 2009-08-26 | 2014-02-17 | Sanofi | Nuevos hidratos cristalinos de fluoroglicósidos heteroaromáticos, productos farmacéuticos que comprenden estos compuestos, y su empleo |
| PE20121350A1 (es) | 2009-10-14 | 2012-10-20 | Xenon Pharmaceuticals Inc | Metodos sinteticos para compuestos espiro-oxoindol |
| PE20121699A1 (es) | 2010-02-26 | 2012-12-22 | Xenon Pharmaceuticals Inc | Composiciones farmaceuticas del compuesto espiro-oxindol para administracion topica |
| WO2011107494A1 (de) | 2010-03-03 | 2011-09-09 | Sanofi | Neue aromatische glykosidderivate, diese verbindungen enthaltende arzneimittel und deren verwendung |
| US8933024B2 (en) | 2010-06-18 | 2015-01-13 | Sanofi | Azolopyridin-3-one derivatives as inhibitors of lipases and phospholipases |
| US8530413B2 (en) | 2010-06-21 | 2013-09-10 | Sanofi | Heterocyclically substituted methoxyphenyl derivatives with an oxo group, processes for preparation thereof and use thereof as medicaments |
| TW201215388A (en) | 2010-07-05 | 2012-04-16 | Sanofi Sa | (2-aryloxyacetylamino)phenylpropionic acid derivatives, processes for preparation thereof and use thereof as medicaments |
| TW201221505A (en) | 2010-07-05 | 2012-06-01 | Sanofi Sa | Aryloxyalkylene-substituted hydroxyphenylhexynoic acids, process for preparation thereof and use thereof as a medicament |
| TW201215387A (en) | 2010-07-05 | 2012-04-16 | Sanofi Aventis | Spirocyclically substituted 1,3-propane dioxide derivatives, processes for preparation thereof and use thereof as a medicament |
| EP2683701B1 (de) | 2011-03-08 | 2014-12-24 | Sanofi | Mit benzyl- oder heteromethylengruppen substituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| US8895547B2 (en) | 2011-03-08 | 2014-11-25 | Sanofi | Substituted phenyl-oxathiazine derivatives, method for producing them, drugs containing said compounds and the use thereof |
| US8871758B2 (en) | 2011-03-08 | 2014-10-28 | Sanofi | Tetrasubstituted oxathiazine derivatives, method for producing them, their use as medicine and drug containing said derivatives and the use thereof |
| WO2012120053A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Verzweigte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| EP2683702B1 (de) | 2011-03-08 | 2014-12-24 | Sanofi | Neue substituierte phenyl-oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
| WO2012120055A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| US8828994B2 (en) | 2011-03-08 | 2014-09-09 | Sanofi | Di- and tri-substituted oxathiazine derivatives, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof |
| EP2683698B1 (de) | 2011-03-08 | 2017-10-04 | Sanofi | Mit adamantan- oder noradamantan substituierte benzyl-oxathiazinderivate, diese verbindungen enthaltende arzneimittel und deren verwendung |
| EP2766349B1 (de) | 2011-03-08 | 2016-06-01 | Sanofi | Mit carbozyklen oder heterozyklen substituierte oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
| WO2013037390A1 (en) | 2011-09-12 | 2013-03-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| WO2013045413A1 (en) | 2011-09-27 | 2013-04-04 | Sanofi | 6-(4-hydroxy-phenyl)-3-alkyl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| TW201636017A (zh) | 2015-02-05 | 2016-10-16 | 梯瓦製藥國際有限責任公司 | 以螺吲哚酮化合物之局部調配物治療帶狀疱疹後遺神經痛之方法 |
| EP3235813A1 (en) | 2016-04-19 | 2017-10-25 | Cidqo 2012, S.L. | Aza-tetra-cyclo derivatives |
| KR102351054B1 (ko) * | 2019-11-11 | 2022-01-14 | 엠비디 주식회사 | 신규한 퀴놀린 화합물 및 이의 용도 |
Family Cites Families (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4439606A (en) * | 1982-05-06 | 1984-03-27 | American Cyanamid Company | Antiatherosclerotic 1-piperazinecarbonyl compounds |
| DE4234295A1 (de) * | 1992-10-12 | 1994-04-14 | Thomae Gmbh Dr K | Carbonsäurederivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
| FR2705343B1 (fr) * | 1993-05-17 | 1995-07-21 | Fournier Ind & Sante | Dérivés de beta,beta-diméthyl-4-pipéridineéthanamine, leur procédé de préparation et leur utilisation en thérapeutique. |
| FR2724656B1 (fr) * | 1994-09-15 | 1996-12-13 | Adir | Nouveaux derives du benzopyranne, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| IL115420A0 (en) * | 1994-09-26 | 1995-12-31 | Zeneca Ltd | Aminoheterocyclic derivatives |
| FR2736053B1 (fr) * | 1995-06-28 | 1997-09-19 | Sanofi Sa | Nouvelles 1-phenylalkyl-1,2,3,6-tetrahydropyridines |
| US6087368A (en) * | 1998-06-08 | 2000-07-11 | Bristol-Myers Squibb Company | Quinazolinone inhibitors of cGMP phosphodiesterase |
| US7294637B2 (en) * | 2000-09-11 | 2007-11-13 | Sepracor, Inc. | Method of treating addiction or dependence using a ligand for a monamine receptor or transporter |
| JP4597480B2 (ja) * | 2001-05-11 | 2010-12-15 | プロキシマゲン・リミテッド | 肥満、ｉｉ型糖尿病およびｃｎｓ疾患の処置のための新規アリールスルホンアミド化合物 |
| US7365205B2 (en) * | 2001-06-20 | 2008-04-29 | Daiichi Sankyo Company, Limited | Diamine derivatives |
| US6547958B1 (en) * | 2001-07-13 | 2003-04-15 | Chevron U.S.A. Inc. | Hydrocarbon conversion using zeolite SSZ-59 |
| US6818772B2 (en) * | 2002-02-22 | 2004-11-16 | Abbott Laboratories | Antagonists of melanin concentrating hormone effects on the melanin concentrating hormone receptor |
| GB0213715D0 (en) * | 2002-06-14 | 2002-07-24 | Syngenta Ltd | Chemical compounds |
| AU2002354054A1 (en) * | 2002-10-18 | 2004-05-04 | Ono Pharmaceutical Co., Ltd. | Spiroheterocyclic derivative compounds and drugs comprising the compounds as the active ingredient |
| DE602004027171D1 (de) * | 2003-04-11 | 2010-06-24 | High Point Pharmaceuticals Llc | Verbindungen mit Aktivität an der 11Beta-Hydroxasteroiddehydrogenase |
| TWI350168B (en) * | 2004-05-07 | 2011-10-11 | Incyte Corp | Amido compounds and their use as pharmaceuticals |
| JP2008504279A (ja) * | 2004-06-24 | 2008-02-14 | インサイト・コーポレイション | アミド化合物およびその医薬としての使用 |
| EP1758580A4 (en) * | 2004-06-24 | 2008-01-16 | Incyte Corp | N-SUBSTITUTED PIPERIDINE AND ITS USE AS A MEDICAMENT |
| JP2008504280A (ja) * | 2004-06-24 | 2008-02-14 | インサイト・コーポレイション | ２−メチルプロパンアミドおよびその医薬としての使用 |
| CA2570694A1 (en) * | 2004-06-24 | 2006-02-02 | Incyte Corporation | Amido compounds and their use as pharmaceuticals |
| WO2006002349A1 (en) * | 2004-06-24 | 2006-01-05 | Incyte Corporation | Amido compounds and their use as pharmaceuticals |
| MX2007001540A (es) * | 2004-08-10 | 2007-04-23 | Incyte Corp | Compuestos amido y sus usos como farmaceuticos. |
| US20060116382A1 (en) * | 2004-11-10 | 2006-06-01 | Wenqing Yao | Lactam compounds and their use as pharmaceuticals |
| KR20070097441A (ko) * | 2004-11-18 | 2007-10-04 | 인사이트 산 디에고 인코포레이티드 | 11-β 하이드록실 스테로이드 데하이드로게나제 유형 1의억제제 및 이를 사용하는 방법 |
| EP1846362A2 (en) * | 2005-01-05 | 2007-10-24 | Abbott Laboratories | Inhibitors of the 11-beta-hydroxysteroid dehydrogenase type 1 enzyme |
| KR100979577B1 (ko) * | 2005-03-03 | 2010-09-01 | 에프. 호프만-라 로슈 아게 | 2형 진성 당뇨병의 치료를 위한11-베타-하이드록시스테로이드 탈수소효소의 억제제로서1-설폰일-피페리딘-3-카복실산 아마이드 유도체 |
| EP1931652A2 (en) * | 2005-09-21 | 2008-06-18 | Incyte Corporation | Amido compounds and their use as pharmaceuticals |
| TW200804382A (en) * | 2005-12-05 | 2008-01-16 | Incyte Corp | Lactam compounds and methods of using the same |
| US7998959B2 (en) * | 2006-01-12 | 2011-08-16 | Incyte Corporation | Modulators of 11-β hydroxyl steroid dehydrogenase type 1, pharmaceutical compositions thereof, and methods of using the same |
| US20070197530A1 (en) * | 2006-01-31 | 2007-08-23 | Yun-Long Li | Amido compounds and their use as pharmaceuticals |
| TW200808807A (en) * | 2006-03-02 | 2008-02-16 | Incyte Corp | Modulators of 11-β hydroxyl steroid dehydrogenase type 1, pharmaceutical compositions thereof, and methods of using the same |
| WO2007103719A2 (en) * | 2006-03-03 | 2007-09-13 | Incyte Corporation | MODULATORS OF 11-β HYDROXYL STEROID DEHYDROGENASE TYPE 1, PHARMACEUTICAL COMPOSITIONS THEREOF, AND METHODS OF USING THE SAME |
| CA2649677A1 (en) * | 2006-05-01 | 2007-11-15 | Incyte Corporation | Tetrasubstituted ureas as modulators of 11-.beta. hydroxyl steroid dehydrogenase type 1 |
| JP2009537564A (ja) * | 2006-05-17 | 2009-10-29 | インサイト・コーポレイション | １１−βヒドロキシルステロイドデヒドロゲナーゼタイプＩの複素環阻害剤およびそれを用いる方法 |
-
2005
- 2005-06-23 WO PCT/US2005/022170 patent/WO2006012173A1/en not_active Ceased
- 2005-06-23 JP JP2007518256A patent/JP2008504274A/ja not_active Withdrawn
- 2005-06-23 US US11/159,863 patent/US20050288317A1/en not_active Abandoned
- 2005-06-23 MX MXPA06014573A patent/MXPA06014573A/es not_active Application Discontinuation
- 2005-06-23 CA CA002569507A patent/CA2569507A1/en not_active Abandoned
- 2005-06-23 CN CNA2005800205246A patent/CN101001850A/zh active Pending
- 2005-06-23 EP EP05762850A patent/EP1758882A4/en not_active Withdrawn
- 2005-06-23 BR BRPI0512630-4A patent/BRPI0512630A/pt not_active IP Right Cessation
- 2005-06-23 AU AU2005267331A patent/AU2005267331A1/en not_active Abandoned
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008531616A (ja) * | 2005-03-03 | 2008-08-14 | エフ．ホフマン−ラ ロシュ アーゲー | ＩＩ型糖尿病の処置用の１１−β−ヒドロキシステロイド・デヒドロゲナーゼのインヒビターとしての１−スルホニル−ピペリジン−３−カルボン酸アミド誘導体 |
| JP2010535834A (ja) * | 2007-08-13 | 2010-11-25 | エフ．ホフマン−ラ ロシュ アーゲー | 新規ピペラジンアミド誘導体 |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2005267331A1 (en) | 2006-02-02 |
| WO2006012173A1 (en) | 2006-02-02 |
| EP1758882A4 (en) | 2008-01-23 |
| CA2569507A1 (en) | 2006-02-02 |
| BRPI0512630A (pt) | 2008-03-25 |
| MXPA06014573A (es) | 2007-03-12 |
| CN101001850A (zh) | 2007-07-18 |
| US20050288317A1 (en) | 2005-12-29 |
| EP1758882A1 (en) | 2007-03-07 |
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