JP5544296B2 - 代謝障害のためのカルボキサミド、スルホンアミド、およびアミン化合物 - Google Patents
代謝障害のためのカルボキサミド、スルホンアミド、およびアミン化合物 Download PDFInfo
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- JP5544296B2 JP5544296B2 JP2010534263A JP2010534263A JP5544296B2 JP 5544296 B2 JP5544296 B2 JP 5544296B2 JP 2010534263 A JP2010534263 A JP 2010534263A JP 2010534263 A JP2010534263 A JP 2010534263A JP 5544296 B2 JP5544296 B2 JP 5544296B2
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- JP
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- Prior art keywords
- piperidin
- alkyl
- yloxy
- phenyl
- trifluoromethyl
- 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.)
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- -1 amine compounds Chemical class 0.000 title claims description 388
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- 229940124530 sulfonamide Drugs 0.000 title description 5
- 208000030159 metabolic disease Diseases 0.000 title description 4
- 150000003456 sulfonamides Chemical class 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims description 449
- 125000000217 alkyl group Chemical group 0.000 claims description 360
- 125000001072 heteroaryl group Chemical group 0.000 claims description 113
- 125000003118 aryl group Chemical group 0.000 claims description 107
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 99
- 125000001188 haloalkyl group Chemical group 0.000 claims description 93
- 229910052799 carbon Inorganic materials 0.000 claims description 70
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 65
- 229910052736 halogen Inorganic materials 0.000 claims description 51
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- 125000004122 cyclic group Chemical group 0.000 claims description 48
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 40
- 150000003839 salts Chemical class 0.000 claims description 36
- 239000012453 solvate Substances 0.000 claims description 31
- 150000001204 N-oxides Chemical class 0.000 claims description 30
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 30
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 29
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- 101000783681 Homo sapiens 5'-AMP-activated protein kinase catalytic subunit alpha-2 Proteins 0.000 claims description 27
- 125000001424 substituent group Chemical group 0.000 claims description 21
- 125000005605 benzo group Chemical group 0.000 claims description 17
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
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- 125000004076 pyridyl group Chemical group 0.000 claims description 7
- IIYPLRFMIACDPN-UHFFFAOYSA-N 1-[(4-fluorophenyl)methyl]-n-[5-[1-[4-(trifluoromethyl)phenyl]piperidin-4-yl]oxy-2,3-dihydro-1h-inden-1-yl]piperidin-4-amine Chemical compound C1=CC(F)=CC=C1CN1CCC(NC2C3=CC=C(OC4CCN(CC4)C=4C=CC(=CC=4)C(F)(F)F)C=C3CC2)CC1 IIYPLRFMIACDPN-UHFFFAOYSA-N 0.000 claims description 6
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- JGGUDZHAKXSMBF-UHFFFAOYSA-N n-[5-[1-[4-(trifluoromethyl)phenyl]piperidin-4-yl]oxy-2,3-dihydro-1h-inden-1-yl]piperidin-4-amine Chemical compound C1=CC(C(F)(F)F)=CC=C1N1CCC(OC=2C=C3CCC(C3=CC=2)NC2CCNCC2)CC1 JGGUDZHAKXSMBF-UHFFFAOYSA-N 0.000 claims description 3
- RTJCPJPIPFHECW-UHFFFAOYSA-N tert-butyl 4-[[6-[1-[4-(trifluoromethyl)phenyl]piperidin-4-yl]oxypyridin-3-yl]sulfonylamino]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1NS(=O)(=O)C(C=N1)=CC=C1OC1CCN(C=2C=CC(=CC=2)C(F)(F)F)CC1 RTJCPJPIPFHECW-UHFFFAOYSA-N 0.000 claims description 3
- MCLGXPUTSWJSRB-UHFFFAOYSA-N 1-(pyridin-4-ylmethyl)-n-[5-[1-[4-(trifluoromethyl)phenyl]piperidin-4-yl]oxy-2,3-dihydro-1h-inden-1-yl]piperidin-4-amine Chemical compound C1=CC(C(F)(F)F)=CC=C1N1CCC(OC=2C=C3CCC(C3=CC=2)NC2CCN(CC=3C=CN=CC=3)CC2)CC1 MCLGXPUTSWJSRB-UHFFFAOYSA-N 0.000 claims description 2
- BYHWWOPUEYHTSB-UHFFFAOYSA-N 4-[[4-[[5-[1-[4-(trifluoromethyl)phenyl]piperidin-4-yl]oxy-2,3-dihydro-1h-inden-1-yl]amino]piperidin-1-yl]methyl]benzonitrile Chemical compound C1=CC(C(F)(F)F)=CC=C1N1CCC(OC=2C=C3CCC(C3=CC=2)NC2CCN(CC=3C=CC(=CC=3)C#N)CC2)CC1 BYHWWOPUEYHTSB-UHFFFAOYSA-N 0.000 claims description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
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- 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
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
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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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- A61P3/06—Antihyperlipidemics
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- A—HUMAN NECESSITIES
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- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
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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
- 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
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/46—Oxygen atoms attached in position 4 having a hydrogen atom as the second substituent in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
-
- 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
- C07D401/12—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 chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
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- Public Health (AREA)
- General Health & Medical Sciences (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Endocrinology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Emergency Medicine (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Hydrogenated Pyridines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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| EP2079694B1 (en) | 2006-12-28 | 2017-03-01 | Rigel Pharmaceuticals, Inc. | N-substituted-heterocycloalkyloxybenzamide compounds and methods of use |
| KR101573091B1 (ko) | 2007-11-16 | 2015-11-30 | 리겔 파마슈티칼스, 인크. | 대사성 장애를 위한 카르복스아미드, 술폰아미드 및 아민 화합물 |
| CA2707047C (en) * | 2007-12-12 | 2017-11-28 | Rigel Pharmaceuticals, Inc. | Carboxamide, sulfonamide and amine compounds for metabolic disorders |
| CA2722139C (en) * | 2008-04-23 | 2017-04-11 | Rigel Pharmaceuticals, Inc. | Carboxamide compounds for the treatment of metabolic disorders |
| HRP20150355T1 (hr) | 2009-01-12 | 2015-06-19 | Pfizer Limited | Sulfonamidni derivati |
| NZ594556A (en) | 2009-01-28 | 2013-11-29 | Rigel Pharmaceuticals Inc | Carboxamide compounds and methods for using the same |
| MX2011013016A (es) | 2009-06-05 | 2012-04-20 | Link Medicine Corp | Derivados de aminopirrolidinona y usos de los mismos. |
| CN102666485A (zh) * | 2009-09-21 | 2012-09-12 | 霍夫曼-拉罗奇有限公司 | 烯烃羟吲哚衍生物及其用于治疗肥胖症,糖尿病和高脂血症的应用 |
| WO2011107494A1 (de) | 2010-03-03 | 2011-09-09 | Sanofi | Neue aromatische glykosidderivate, diese verbindungen enthaltende arzneimittel und deren verwendung |
| WO2011115106A1 (ja) * | 2010-03-16 | 2011-09-22 | 国立大学法人 東京大学 | 擬似運動療法のための医薬 |
| WO2011123681A1 (en) * | 2010-03-31 | 2011-10-06 | Rigel Pharmaceuticals, Inc. | Methods for using carboxamide, sulfonamide and amine compounds |
| TW201211053A (en) * | 2010-05-10 | 2012-03-16 | Nissan Chemical Ind Ltd | Spiro compound and drug for activating adiponectin receptor |
| 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 |
| US8697911B2 (en) | 2010-07-07 | 2014-04-15 | Boehringer Ingelheim International Gmbh | Rho kinase inhibitors |
| US9079880B2 (en) | 2010-07-07 | 2015-07-14 | Boehringer Ingelheim International Gmbh | Rho kinase inhibitors |
| EP2590972B1 (en) | 2010-07-09 | 2015-01-21 | Pfizer Limited | N-sulfonylbenzamides as inhibitors of voltage-gated sodium channels |
| CA2806341C (en) | 2010-07-29 | 2020-03-24 | Rigel Pharmaceuticals, Inc. | Ampk-activating heterocyclic compounds and methods for using the same |
| JP5769326B2 (ja) | 2010-10-19 | 2015-08-26 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Rhoキナーゼ阻害薬 |
| US9005909B2 (en) | 2011-01-06 | 2015-04-14 | Rigel Pharmaceuticals, Inc. | Whole blood assay for measuring AMPK activation |
| 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 |
| US9409884B2 (en) * | 2012-02-01 | 2016-08-09 | Rigel Pharmaceuticals, Inc. | 5- or 6-substituted benzofuran-2-carboxamide compounds and methods for using them |
| US8889730B2 (en) | 2012-04-10 | 2014-11-18 | Pfizer Inc. | Indole and indazole compounds that activate AMPK |
| JP6233855B2 (ja) * | 2012-08-08 | 2017-11-22 | ノバルティス・ティーアゲズントハイト・アクチェンゲゼルシャフトNovartis Tiergesundheit Ag | 殺虫剤としての置換されたアジン類 |
| US8729263B2 (en) | 2012-08-13 | 2014-05-20 | Novartis Ag | 1,4-disubstituted pyridazine analogs there of and methods for treating SMN-deficiency-related conditions |
| CA2905242C (en) | 2013-03-15 | 2016-11-29 | Pfizer Inc. | Indole compounds that activate ampk |
| MX2020011652A (es) | 2013-07-31 | 2022-09-27 | Novartis Ag | Derivados de piridazina 1,4-disustituida, y su uso para el tratamiento de afecciones relacionadas con la deficiencia de smn. |
| WO2015046595A1 (ja) | 2013-09-30 | 2015-04-02 | 国立大学法人東京大学 | アディポネクチン受容体活性化化合物 |
| EP3231802B1 (en) * | 2014-12-08 | 2021-05-05 | Jiangsu Hengrui Medicine Co., Ltd. | Pyridine-2-carboxamide derivatives, preparation method therefor and pharmaceutical uses thereof |
| EP3959205B1 (en) * | 2019-04-26 | 2025-11-12 | Merck Sharp & Dohme LLC | Process for the preparation of intermediates useful for making (2s,5r)-7-oxo-n-piperidin-4-yl-6-(sulfoxy)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide |
| WO2022072397A1 (en) | 2020-09-30 | 2022-04-07 | Bioverativ Therapeutics Inc. | Ampk activators and methods of use thereof |
Family Cites Families (69)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8820115D0 (en) * | 1988-08-24 | 1988-09-28 | Ici Plc | Insecticidal compounds |
| US6137002A (en) * | 1993-07-22 | 2000-10-24 | Eli Lilly And Company | Glycoprotein IIb/IIIa antagonists |
| NZ331490A (en) | 1996-03-28 | 2000-06-23 | Glaxo Group Ltd | Pyrrolopyrrolone derivatives for the treatment or prophylaxis of inflammatory disease such as chronic bronchitis, obstructive pulmonary disease and asthma |
| GB9715584D0 (en) | 1997-07-23 | 1997-10-01 | Eisai Co Ltd | Compounds |
| DE19738615A1 (de) * | 1997-09-04 | 1999-03-11 | Clariant Gmbh | Neue Lichtschutzmittel auf Basis von sterisch gehinderten Aminen |
| US6589954B1 (en) | 1998-05-22 | 2003-07-08 | Scios, Inc. | Compounds and methods to treat cardiac failure and other disorders |
| EP1107758A2 (en) | 1998-08-28 | 2001-06-20 | Scios Inc. | Use of piperidines and/or piperazines as inhibitors of p38-alpha kinase |
| US6953855B2 (en) * | 1998-12-11 | 2005-10-11 | Targacept, Inc. | 3-substituted-2(arylalkyl)-1-azabicycloalkanes and methods of use thereof |
| DK1218380T3 (da) * | 1999-10-08 | 2004-03-15 | Gruenenthal Gmbh | Bicykliske imidazo-3-yl-aminoderivater substitueret i seksledsringen |
| US6436965B1 (en) | 2000-03-02 | 2002-08-20 | Merck Frosst Canada & Co. | PDE IV inhibiting amides, compositions and methods of treatment |
| US7273868B2 (en) * | 2000-04-28 | 2007-09-25 | Tanabe Seiyaku Co., Ltd. | Pyrazine derivatives |
| AU2001273040A1 (en) | 2000-06-27 | 2002-01-08 | Du Pont Pharmaceuticals Company | Factor xa inhibitors |
| DE10050663A1 (de) * | 2000-10-13 | 2002-04-18 | Gruenenthal Gmbh | Verwendung von substituierten Imidazo[1,2-a]pyridin-, -pyrimidin- und pyrazin-3-yl-amin-Derivaten zur Herstellung von Medikamenten zur NOS-Inhibierung |
| HU230302B1 (hu) * | 2000-10-20 | 2015-12-28 | Eisai R&D Management Co., Ltd. | Nitrogéntartalmú aromás származékok és ezeket tartalmazó gyógyászati készítmények |
| WO2002089749A2 (en) | 2001-05-10 | 2002-11-14 | Abbott Gmbh & Co.Kg | Arylsulfonamide ethers, and methods of use thereof |
| BR0212123A (pt) | 2001-08-24 | 2004-07-20 | Upjohn Co | 7-aza[2.2.1]biciclo-heptanos substituìdos com arila para o tratamento de doenças |
| EP1425286B1 (en) | 2001-09-12 | 2007-02-28 | Pharmacia & Upjohn Company LLC | Substituted 7-aza-[2.2.1]bicycloheptanes for the treatment of diseases |
| CA2476681A1 (en) | 2002-02-19 | 2003-08-28 | Bruce N. Rogers | Fused bicyclic-n-bridged-heteroaromatic carboxamides for the treatment of disease |
| MXPA04007083A (es) * | 2002-02-20 | 2004-10-29 | Upjohn Co | Compuestos azabiciclicos para el tratamiento de enfermedades. |
| AU2003245669A1 (en) | 2002-06-21 | 2004-01-06 | Cellular Genomics, Inc. | Certain aromatic monocycles as kinase modulators |
| AU2003254157A1 (en) * | 2002-07-24 | 2004-02-09 | Ptc Therapeutics, Inc. | Acetylamino benzoic acid compounds and their use for nonsense suppression and the treatment of disease |
| EP1569646A2 (en) | 2002-12-13 | 2005-09-07 | Smithkline Beecham Corporation | Piperidine derivatives as ccr5 antagonists |
| US7208491B2 (en) * | 2003-02-07 | 2007-04-24 | Hoffmann-La Roche Inc. | N-monoacylated o-phenylenediamines |
| GB2400101A (en) | 2003-03-28 | 2004-10-06 | Biofocus Discovery Ltd | Compounds capable of binding to the active site of protein kinases |
| GB0314054D0 (en) | 2003-06-17 | 2003-07-23 | Pfizer Ltd | Amide derivatives as selective serotonin re-uptake inhibitors |
| TWI372050B (en) | 2003-07-03 | 2012-09-11 | Astex Therapeutics Ltd | (morpholin-4-ylmethyl-1h-benzimidazol-2-yl)-1h-pyrazoles |
| EP1663204B1 (en) | 2003-08-29 | 2014-05-07 | Exelixis, Inc. | C-kit modulators and methods of use |
| JP2007516256A (ja) | 2003-12-12 | 2007-06-21 | イーライ リリー アンド カンパニー | オピオイド受容体拮抗物質 |
| US7544803B2 (en) * | 2004-01-23 | 2009-06-09 | Amgen Inc. | Vanilloid receptor ligands and their use in treatments |
| US20050234095A1 (en) * | 2004-03-25 | 2005-10-20 | Wenge Xie | Indazoles, benzothiazoles, benzoisothiazoles, benzisoxazoles, and preparation and uses thereof |
| PE20060315A1 (es) | 2004-05-24 | 2006-05-15 | Irm Llc | Compuestos de tiazol como moduladores de ppar |
| CN1960727B (zh) * | 2004-06-02 | 2011-02-16 | 霍夫曼-拉罗奇有限公司 | 用作组胺-3受体的配体的萘衍生物 |
| CN1972926B (zh) * | 2004-06-21 | 2011-02-16 | 霍夫曼-拉罗奇有限公司 | 作为组胺受体拮抗剂的吲哚衍生物 |
| WO2006038594A1 (ja) * | 2004-10-04 | 2006-04-13 | Ono Pharmaceutical Co., Ltd. | N型カルシウムチャネル阻害薬 |
| ATE517882T1 (de) | 2004-10-19 | 2011-08-15 | Hoffmann La Roche | Chinolinderivate |
| AU2005300150A1 (en) | 2004-10-29 | 2006-05-04 | Astrazeneca Ab | Novel sulphonamide derivatives as glucocorticoid receptor modulators for the treatment of inflammatory diseases |
| CN101098870B (zh) | 2004-11-08 | 2010-11-03 | 万有制药株式会社 | 新型稠环咪唑衍生物 |
| US20080125432A1 (en) | 2004-12-01 | 2008-05-29 | Devgen Nv | 5-Carboxamido Substituted Thiazole Derivatives that Interact With Ion Channels, In Particular With Ion Channels From the Kv Family |
| BRPI0517211B8 (pt) | 2004-12-17 | 2021-05-25 | Glenmark Pharmaceuticals Sa | composto, composição farmacêutica e seu uso. |
| EP1838312A4 (en) | 2004-12-17 | 2010-01-20 | Smithkline Beecham Corp | CHEMICAL COMPOUNDS |
| GB0428235D0 (en) | 2004-12-23 | 2005-01-26 | Glaxo Group Ltd | Novel compounds |
| US20060187891A1 (en) | 2005-02-24 | 2006-08-24 | Jussi-Pekka Sairanen | Provision of services in a communication system |
| CA2599987A1 (en) | 2005-03-03 | 2006-09-08 | Sirtris Pharmaceuticals, Inc. | Fused heterocyclic compounds and their use as sirtuin modulators |
| US7893267B2 (en) | 2005-03-14 | 2011-02-22 | High Point Pharmaceuticals, Llc | Benzazole derivatives, compositions, and methods of use as β-secretase inhibitors |
| EP1863810A4 (en) | 2005-03-22 | 2010-03-31 | Astrazeneca Ab | NEW TETRAHYDRO-1H-PYRIDO [4,3-B] INDOLDERIVATE AS CB1 'RECEPTOR LIGANDS |
| GB0508472D0 (en) | 2005-04-26 | 2005-06-01 | Glaxo Group Ltd | Compounds |
| JP2009500419A (ja) | 2005-07-05 | 2009-01-08 | アリックス セラピューティクス、インコーポレイテッド | 立体異性体のピリジル及びピリドニル化合物並びに消化管障害及び中枢神経系障害の治療方法 |
| CA2622677A1 (en) * | 2005-09-23 | 2007-04-05 | Richard Schumacher | Indazoles, benzothiazoles, benzoisothiazoles, benzisoxazoles, pyrazolopyridines, isothiazolopyridines, and preparation and uses thereof |
| KR101047204B1 (ko) * | 2005-11-30 | 2011-07-06 | 에프. 호프만-라 로슈 아게 | H3 조절제로서 사용하기 위한1,1-다이옥소-싸이오모폴린일 인돌일 메탄온 유도체 |
| ES2342979T3 (es) * | 2005-11-30 | 2010-07-20 | F. Hoffmann-La Roche Ag | Derivados de indol-2-carboxamida sustituidos en 5. |
| CN101316840B (zh) * | 2005-11-30 | 2012-08-08 | 霍夫曼-拉罗奇有限公司 | 1,5-取代的吲哚-2-基酰胺衍生物 |
| WO2007075688A2 (en) * | 2005-12-21 | 2007-07-05 | Schering Corporation | Substituted aniline derivatives useful as histamine h3 antagonists |
| JP2009524689A (ja) | 2006-01-25 | 2009-07-02 | スミスクライン ビーチャム コーポレーション | 化合物 |
| TW200738711A (en) | 2006-01-25 | 2007-10-16 | Smithkline Beecham Corp | Chemical compounds |
| WO2007098086A2 (en) * | 2006-02-17 | 2007-08-30 | Avalon Pharmaceuticals | Hydroxypiperidine derivatives and uses thereof |
| WO2007099423A1 (en) | 2006-03-02 | 2007-09-07 | Pfizer Products Inc. | 1-pyrrolidine indane derivatives as histamine-3 receptor antagonists |
| NL2000581C2 (nl) | 2006-04-20 | 2008-01-03 | Pfizer Prod Inc | Aangecondenseerde fenylamidoheterocyclische verbindingen. |
| WO2007125405A2 (en) * | 2006-05-01 | 2007-11-08 | Pfizer Products Inc. | Substituted 2-amino-fused heterocyclic compounds |
| EP2032566A4 (en) | 2006-06-12 | 2009-07-08 | Merck Frosst Canada Ltd | AZETIDINE DERIVATIVES AS INHIBITORS OF STEAROYL-COENZYME-A-DELTA-9-DESATURASE |
| CA2654098A1 (en) | 2006-06-13 | 2007-12-21 | Merck Frosst Canada Ltd. | Azacyclopentane derivatives as inhibitors of stearoyl-coenzyme a delta-9 desaturase |
| TW200821303A (en) | 2006-08-08 | 2008-05-16 | Speedel Experimenta Ag | Organic compounds |
| EP2079694B1 (en) * | 2006-12-28 | 2017-03-01 | Rigel Pharmaceuticals, Inc. | N-substituted-heterocycloalkyloxybenzamide compounds and methods of use |
| JP2010527915A (ja) * | 2007-04-26 | 2010-08-19 | アバロン ファーマシューティカルズ,インコーポレイテッド | 多重環化合物及びその用途 |
| SG183049A1 (en) * | 2007-07-20 | 2012-08-30 | Nerviano Medical Sciences Srl | Substituted indazole derivatives active as kinase inhibitors |
| KR101573091B1 (ko) | 2007-11-16 | 2015-11-30 | 리겔 파마슈티칼스, 인크. | 대사성 장애를 위한 카르복스아미드, 술폰아미드 및 아민 화합물 |
| CA2707047C (en) * | 2007-12-12 | 2017-11-28 | Rigel Pharmaceuticals, Inc. | Carboxamide, sulfonamide and amine compounds for metabolic disorders |
| EA018703B1 (ru) * | 2008-04-07 | 2013-10-30 | Айрм Ллк | Соединения и композиции в качестве модуляторов активности gpr119 |
| CA2722139C (en) | 2008-04-23 | 2017-04-11 | Rigel Pharmaceuticals, Inc. | Carboxamide compounds for the treatment of metabolic disorders |
| JP2010090067A (ja) * | 2008-10-09 | 2010-04-22 | Taisho Pharmaceutical Co Ltd | 含窒素複素環誘導体 |
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