EA009647B1 - Арилсульфонамидные соединения и их применение для лечения ожирения и диабета типа ii - Google Patents
Арилсульфонамидные соединения и их применение для лечения ожирения и диабета типа ii Download PDFInfo
- Publication number
- EA009647B1 EA009647B1 EA200301232A EA200301232A EA009647B1 EA 009647 B1 EA009647 B1 EA 009647B1 EA 200301232 A EA200301232 A EA 200301232A EA 200301232 A EA200301232 A EA 200301232A EA 009647 B1 EA009647 B1 EA 009647B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- amino
- phenyl
- diazepan
- hydrochloride
- benzenesulfonamide
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 130
- 238000011282 treatment Methods 0.000 title claims abstract description 13
- 208000008589 Obesity Diseases 0.000 title claims abstract description 12
- 235000020824 obesity Nutrition 0.000 title claims abstract description 12
- 208000001072 type 2 diabetes mellitus Diseases 0.000 title claims abstract description 11
- -1 [2- {ethyl [(3-fluorophenyl) sulfonyl] amino} -4- (4-methyl-1-piperazinyl) phenyl] -3-fluorobenzenesulfonamide Chemical compound 0.000 claims description 236
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 131
- 238000000034 method Methods 0.000 claims description 125
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 78
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 63
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 34
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 28
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 18
- 125000000217 alkyl group Chemical group 0.000 claims description 18
- 239000002253 acid Substances 0.000 claims description 15
- 229920006395 saturated elastomer Polymers 0.000 claims description 14
- BPSUJSDZHLTNJR-UHFFFAOYSA-N sulfamide;hydrochloride Chemical compound Cl.NS(N)(=O)=O BPSUJSDZHLTNJR-UHFFFAOYSA-N 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 11
- 150000001412 amines Chemical class 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 125000000623 heterocyclic group Chemical group 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 10
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- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 7
- 230000000694 effects Effects 0.000 claims description 7
- 241001139947 Mida Species 0.000 claims description 6
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- QUDRWUPVTUGQOL-UHFFFAOYSA-N tert-butyl 4-[3-(methanesulfonamido)-4-nitrophenyl]-1,4-diazepane-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCCN1C1=CC=C([N+]([O-])=O)C(NS(C)(=O)=O)=C1 QUDRWUPVTUGQOL-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/10—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more 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
-
- 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
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- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
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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
- A61P25/24—Antidepressants
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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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- 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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- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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
- C07D215/36—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/08—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 not condensed with other rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/12—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/135—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
-
- 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
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Diabetes (AREA)
- Psychiatry (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pain & Pain Management (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Child & Adolescent Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Quinoline Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
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| SE0101659A SE0101659D0 (sv) | 2001-05-11 | 2001-05-11 | New compounds |
| SE0101660A SE0101660D0 (sv) | 2001-05-11 | 2001-05-11 | New compounds |
| US29410201P | 2001-05-29 | 2001-05-29 | |
| US29413201P | 2001-05-29 | 2001-05-29 | |
| SE0101958A SE0101958D0 (sv) | 2001-06-05 | 2001-06-05 | New compounds |
| PCT/SE2002/000906 WO2002092585A1 (en) | 2001-05-11 | 2002-05-08 | Novel, arylsusfonamide compounds for the treatment of obesity, type ii diabetes and cns-disorders |
Publications (2)
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| EA200301232A1 EA200301232A1 (ru) | 2004-04-29 |
| EA009647B1 true EA009647B1 (ru) | 2008-02-28 |
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| JP (2) | JP4597480B2 (enExample) |
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| CN (1) | CN1329382C (enExample) |
| AU (1) | AU2002303061B2 (enExample) |
| BR (1) | BR0209558A (enExample) |
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| IL (3) | IL158593A0 (enExample) |
| MX (1) | MXPA03010232A (enExample) |
| NO (1) | NO326690B1 (enExample) |
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| MXPA03010232A (es) * | 2001-05-11 | 2004-03-16 | Biovitrum Ab | Compuestos de arilsulfonamida, para el tratamiento de la obesidad, de la diabetes tipo ii y de trastornos del sistema nervioso central. |
| US7718650B2 (en) * | 2001-05-11 | 2010-05-18 | Biovitrum Ab | Aryl sulfonamide compounds for treating obesity |
| US20020197228A1 (en) * | 2001-05-29 | 2002-12-26 | Lasala William Kater | Skin care kit |
| CN100457726C (zh) | 2001-06-11 | 2009-02-04 | 比奥维特罗姆股份公开公司 | 取代的磺酰胺化合物、其制备方法及其作为治疗cns疾病、肥胖和ⅱ型糖尿病的药物的应用 |
| US7354923B2 (en) * | 2001-08-10 | 2008-04-08 | Palatin Technologies, Inc. | Piperazine melanocortin-specific compounds |
| WO2003013571A1 (en) | 2001-08-10 | 2003-02-20 | Palatin Technologies, Inc. | Peptidomimetics of biologically active metallopeptides |
| US7655658B2 (en) | 2001-08-10 | 2010-02-02 | Palatin Technologies, Inc. | Thieno [2,3-D]pyrimidine-2,4-dione melanocortin-specific compounds |
| US7732451B2 (en) | 2001-08-10 | 2010-06-08 | Palatin Technologies, Inc. | Naphthalene-containing melanocortin receptor-specific small molecule |
| US7718802B2 (en) | 2001-08-10 | 2010-05-18 | Palatin Technologies, Inc. | Substituted melanocortin receptor-specific piperazine compounds |
| US7456184B2 (en) | 2003-05-01 | 2008-11-25 | Palatin Technologies Inc. | Melanocortin receptor-specific compounds |
| IL163608A0 (en) * | 2002-02-28 | 2005-12-18 | Univ Temple | Amino-substituted sulfonanilides and derivatives thereof for treating proliferative disorders |
| JP4754821B2 (ja) | 2002-06-20 | 2011-08-24 | プロキシマゲン・リミテッド | 肥満症、ｉｉ型糖尿病およびｃｎｓ障害の治療に有用な新規化合物 |
| CN1662521A (zh) * | 2002-06-20 | 2005-08-31 | 比奥维特罗姆股份公司 | 可用于治疗肥胖、ii型糖尿病和cns障碍的新化合物 |
| GB0224830D0 (en) | 2002-10-24 | 2002-12-04 | Sterix Ltd | Compound |
| SE0203754D0 (sv) * | 2002-12-17 | 2002-12-17 | Astrazeneca Ab | New compounds |
| SE0203753D0 (sv) * | 2002-12-17 | 2002-12-17 | Astrazeneca Ab | New compounds |
| WO2004073634A2 (en) * | 2003-02-20 | 2004-09-02 | Encysive Pharmaceuticals Inc. | Phenylenediamine urotensin-ii receptor antagonists and ccr-9 antagonists |
| US7968548B2 (en) | 2003-05-01 | 2011-06-28 | Palatin Technologies, Inc. | Melanocortin receptor-specific piperazine compounds with diamine groups |
| US7727990B2 (en) | 2003-05-01 | 2010-06-01 | Palatin Technologies, Inc. | Melanocortin receptor-specific piperazine and keto-piperazine compounds |
| US7727991B2 (en) | 2003-05-01 | 2010-06-01 | Palatin Technologies, Inc. | Substituted melanocortin receptor-specific single acyl piperazine compounds |
| MXPA05013365A (es) * | 2003-06-20 | 2006-04-05 | Arena Pharm Inc | Derivados de n-fenil-piperazina y metodos para profilaxis o tratamiento de enfermedades asociadas con el receptor 5ht2c. |
| US20050201965A1 (en) * | 2004-03-11 | 2005-09-15 | The Procter & Gamble Company | Personal cleansing compositions |
| US7709484B1 (en) | 2004-04-19 | 2010-05-04 | Palatin Technologies, Inc. | Substituted melanocortin receptor-specific piperazine compounds |
| JP2007537275A (ja) | 2004-05-12 | 2007-12-20 | ケモセントリックス， インコーポレイテッド | アリールスルホンアミド |
| MXPA06014573A (es) * | 2004-06-24 | 2007-03-12 | Incyte Corp | Compuestos amido y su uso como farmaceuticos. |
| EP1768954A4 (en) | 2004-06-24 | 2008-05-28 | Incyte Corp | 2-METHYLPROPANAMIDES AND THEIR USE AS PHARMACEUTICALS |
| EP1809619A1 (en) * | 2004-10-21 | 2007-07-25 | Transtech Pharma, Inc. | Bissulfonamide compounds as agonists of galr1, compositions, and methods of use |
| JP2008523100A (ja) * | 2004-12-13 | 2008-07-03 | アリーナ ファーマシューティカルズ， インコーポレイテッド | ５ｈｔ２ｃ受容体に関連した疾患の治療に有用な５ｈｔ２ｃ受容体のモジュレータとしてのｎ−ビアリール及びｎ−アリールヘテロアリール２−置換ピペラジン誘導体 |
| EP1695971A1 (en) * | 2004-12-30 | 2006-08-30 | Laboratorios Del Dr. Esteve, S.A. | Substituted phenyl-piperazine compounds, their preparation and use in medicaments |
| EP1676842A1 (en) * | 2004-12-30 | 2006-07-05 | Laboratorios Del Dr. Esteve, S.A. | Nitro-substituted phenyl-piperazine compounds, their preparation and use in medicaments |
| JP5186219B2 (ja) | 2005-01-25 | 2013-04-17 | エピックス デラウェア， インコーポレイテッド | 置換アリールアミン化合物および５−ｈｔ６調節因子としてのその使用 |
| CN101404987A (zh) * | 2006-01-20 | 2009-04-08 | 史密丝克莱恩比彻姆公司 | 磺酰胺衍生物在治疗代射和神经系统疾病中的用途 |
| TW200812961A (en) * | 2006-04-19 | 2008-03-16 | Abbott Gmbh & Co Kg | Heterocyclic compounds suitable for treating disorders that respond to modulation of the serotonin 5HT6 receptor |
| US7834017B2 (en) | 2006-08-11 | 2010-11-16 | Palatin Technologies, Inc. | Diamine-containing, tetra-substituted piperazine compounds having identical 1- and 4-substituents |
| WO2009137597A1 (en) * | 2008-05-06 | 2009-11-12 | The Trustees Of Columbia University In The City Of New York | COMPOUNDS THAT INHIBIT PRODUCTION OF sAPPβ AND Aβ AND USES THEREOF |
| WO2010051064A1 (en) | 2008-10-30 | 2010-05-06 | The Trustees Of Columbia University In The City Of New York | COMPOUNDS THAT INHIBIT NFκB ACTIVITY |
| CA2759482A1 (en) | 2009-04-30 | 2010-11-04 | Abbott Gmbh & Co. Kg | N-phenyl-(piperazinyl or homopiperazinyl)-benzenesulfonamide or benzenesulfonyl-phenyl-(piperazine or homopiperazine) compounds suitable for treating disorders that respond to modulation of the serotonin 5-ht6 receptor |
| US8343959B2 (en) | 2009-04-30 | 2013-01-01 | Abbott Gmbh & Co. Kg | N-phenyl-(piperazinyl or homopiperazinyl)-benzenesulfonamide or benzenesulfonyl-phenyl-(piperazine or homopiperazine) compounds suitable for treating disorders that respond to modulation of the serotonin 5-HT6 receptor |
| MX2011011515A (es) | 2009-04-30 | 2012-01-30 | Abbott Gmbh & Co Kg | Compuestos de bencensulfonanilida adecuados para tratar trastornos que responden a la modulacion del receptor de serotonina 5-ht6. |
| CA2759491A1 (en) | 2009-04-30 | 2010-11-04 | Abbott Gmbh & Co. Kg. | Benzenesulfonanilide compounds suitable for treating disorders that respond to modulation of the serotonin 5-ht6 receptor |
| ES2526675T3 (es) | 2010-07-09 | 2015-01-14 | Pfizer Limited | N-sulfonilbenzamidas como inhibidores de los canales de sodio dependientes de voltaje |
| WO2012059431A1 (en) | 2010-11-01 | 2012-05-10 | Abbott Gmbh & Co. Kg | Benzenesulfonyl or sulfonamide compounds suitable for treating disorders that respond to the modulation of the serotonin 5-ht6 receptor |
| WO2012059432A1 (en) | 2010-11-01 | 2012-05-10 | Abbott Gmbh & Co. Kg | N-phenyl-(homo)piperazinyl-benzenesulfonyl or benzenesulfonamide compounds suitable for treating disorders that respond to the modulation of the 5-ht6 receptor |
| TWI754702B (zh) * | 2016-12-28 | 2022-02-11 | 德商Ｕｃｂ製藥有限公司 | （氮雜）吲哚－和苯並呋喃－３－磺醯胺類 |
Citations (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2033597A5 (en) * | 1969-02-28 | 1970-12-04 | Ugine Kuhlmann | Green phthalocyanine metal dyes |
| DE2239846A1 (de) * | 1972-08-12 | 1974-02-14 | Hoechst Ag | Basisch substituierte benzol-1,3disulfonamide und verfahren zu ihrer herstellung |
| DE2334562A1 (de) * | 1973-07-07 | 1975-01-30 | Hoechst Ag | Basisch substituierte benzol-1,3-disulfonamide und verfahren zu ihrer herstellung |
| DE2459394A1 (de) * | 1974-12-16 | 1976-06-24 | Hoechst Ag | Basisch substituierte benzol-1,3- disulfonamide und verfahren zu ihrer herstellung |
| EP0331232A2 (en) * | 1988-02-29 | 1989-09-06 | Janssen Pharmaceutica N.V. | 5-lipoxygenase inhibiting 4-(4-phenyl-1-piperazinyl)phenols |
| EP0815861A1 (de) * | 1996-06-28 | 1998-01-07 | F. Hoffmann-La Roche Ag | Sulfonamide und ihre Verwendung |
| WO1998006697A1 (en) * | 1996-08-15 | 1998-02-19 | Schering Corporation | Ether muscarinic antagonists |
| WO1998027081A1 (en) * | 1996-12-19 | 1998-06-25 | Smithkline Beecham Plc | Sulphonamide derivatives, process for their preparation, and their use as medicaments |
| WO1999002502A2 (en) * | 1997-07-11 | 1999-01-21 | Smithkline Beecham Plc | Sulphonamide derivatives being 5-ht6 receptor antagonists and process for their preparation |
| WO1999037623A2 (en) * | 1998-01-22 | 1999-07-29 | Smithkline Beecham Plc | Sulphonamide derivatives for treatment of cns disorders |
| WO1999038845A1 (en) * | 1998-01-29 | 1999-08-05 | Tularik Inc. | Ppar-gamma modulators |
| WO1999042465A2 (en) * | 1998-02-18 | 1999-08-26 | Smithkline Beecham Plc | Sulphonamide derivatives being 5-ht6 receptor antagonists and process for their preparation |
| WO2000005225A1 (en) * | 1998-07-20 | 2000-02-03 | Merck Patent Gmbh | Biphenyl derivatives |
| WO2000012623A2 (en) * | 1998-08-28 | 2000-03-09 | Smithkline Beecham P.L.C. | Use of 5-th receptor antagonists for the treatment of parkinson's disease |
| WO2000012073A1 (en) * | 1998-08-28 | 2000-03-09 | Smithkline Beecham P.L.C. | Use of 5ht-6 antagonists |
| WO2001016096A2 (de) * | 1999-09-01 | 2001-03-08 | Aventis Pharma Deutschland Gmbh | Verwendung von bissulfonamiden zur herstellung von medikamenten zur prophylaxe oder behandlung von hyperlipidämie |
| WO2001016094A1 (de) * | 1999-09-01 | 2001-03-08 | Aventis Pharma Deutschland Gmbh | Sulfonylcarboxamidderivate, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL7310889A (enExample) * | 1972-08-12 | 1974-02-14 | ||
| DE19541146A1 (de) * | 1995-10-25 | 1997-04-30 | Schering Ag | Imidazolderivate und deren Verwendung als Stickstoffmonoxid-Synthase-Inhibitoren |
| US6943159B1 (en) * | 1998-02-18 | 2005-09-13 | Neurosearch A/S | Compounds and their use as positive AMPA receptor modulators |
| US6399617B1 (en) * | 2000-07-21 | 2002-06-04 | Biovitrum Ab | Use |
| MXPA03010232A (es) * | 2001-05-11 | 2004-03-16 | Biovitrum Ab | Compuestos de arilsulfonamida, para el tratamiento de la obesidad, de la diabetes tipo ii y de trastornos del sistema nervioso central. |
-
2002
- 2002-05-08 MX MXPA03010232A patent/MXPA03010232A/es not_active Application Discontinuation
- 2002-05-08 PL PL02366619A patent/PL366619A1/xx not_active Application Discontinuation
- 2002-05-08 CN CNB028096142A patent/CN1329382C/zh not_active Expired - Fee Related
- 2002-05-08 IL IL15859302A patent/IL158593A0/xx unknown
- 2002-05-08 NZ NZ528450A patent/NZ528450A/en unknown
- 2002-05-08 JP JP2002589470A patent/JP4597480B2/ja not_active Expired - Fee Related
- 2002-05-08 AU AU2002303061A patent/AU2002303061B2/en not_active Ceased
- 2002-05-08 BR BR0209558-0A patent/BR0209558A/pt not_active IP Right Cessation
- 2002-05-08 KR KR1020097014381A patent/KR20090092832A/ko not_active Ceased
- 2002-05-08 CA CA002443724A patent/CA2443724C/en not_active Expired - Fee Related
- 2002-05-08 EP EP02769640A patent/EP1406884A1/en not_active Withdrawn
- 2002-05-08 EA EA200301232A patent/EA009647B1/ru not_active IP Right Cessation
- 2002-05-08 WO PCT/SE2002/000906 patent/WO2002092585A1/en not_active Ceased
- 2002-05-10 US US10/143,335 patent/US7173035B2/en not_active Expired - Fee Related
- 2002-05-13 US US10/144,677 patent/US6969710B2/en not_active Expired - Fee Related
-
2003
- 2003-10-23 IL IL158593A patent/IL158593A/en not_active IP Right Cessation
- 2003-11-10 NO NO20034996A patent/NO326690B1/no not_active IP Right Cessation
-
2005
- 2005-08-30 US US11/215,173 patent/US7566715B2/en not_active Expired - Fee Related
- 2005-08-30 US US11/214,523 patent/US7319097B2/en not_active Expired - Fee Related
-
2008
- 2008-10-27 IL IL194950A patent/IL194950A0/en unknown
-
2010
- 2010-07-12 JP JP2010157953A patent/JP2011016801A/ja not_active Withdrawn
Patent Citations (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2033597A5 (en) * | 1969-02-28 | 1970-12-04 | Ugine Kuhlmann | Green phthalocyanine metal dyes |
| DE2239846A1 (de) * | 1972-08-12 | 1974-02-14 | Hoechst Ag | Basisch substituierte benzol-1,3disulfonamide und verfahren zu ihrer herstellung |
| DE2334562A1 (de) * | 1973-07-07 | 1975-01-30 | Hoechst Ag | Basisch substituierte benzol-1,3-disulfonamide und verfahren zu ihrer herstellung |
| DE2459394A1 (de) * | 1974-12-16 | 1976-06-24 | Hoechst Ag | Basisch substituierte benzol-1,3- disulfonamide und verfahren zu ihrer herstellung |
| EP0331232A2 (en) * | 1988-02-29 | 1989-09-06 | Janssen Pharmaceutica N.V. | 5-lipoxygenase inhibiting 4-(4-phenyl-1-piperazinyl)phenols |
| EP0815861A1 (de) * | 1996-06-28 | 1998-01-07 | F. Hoffmann-La Roche Ag | Sulfonamide und ihre Verwendung |
| WO1998006697A1 (en) * | 1996-08-15 | 1998-02-19 | Schering Corporation | Ether muscarinic antagonists |
| WO1998027081A1 (en) * | 1996-12-19 | 1998-06-25 | Smithkline Beecham Plc | Sulphonamide derivatives, process for their preparation, and their use as medicaments |
| WO1999002502A2 (en) * | 1997-07-11 | 1999-01-21 | Smithkline Beecham Plc | Sulphonamide derivatives being 5-ht6 receptor antagonists and process for their preparation |
| WO1999037623A2 (en) * | 1998-01-22 | 1999-07-29 | Smithkline Beecham Plc | Sulphonamide derivatives for treatment of cns disorders |
| WO1999038845A1 (en) * | 1998-01-29 | 1999-08-05 | Tularik Inc. | Ppar-gamma modulators |
| WO1999042465A2 (en) * | 1998-02-18 | 1999-08-26 | Smithkline Beecham Plc | Sulphonamide derivatives being 5-ht6 receptor antagonists and process for their preparation |
| WO2000005225A1 (en) * | 1998-07-20 | 2000-02-03 | Merck Patent Gmbh | Biphenyl derivatives |
| WO2000012623A2 (en) * | 1998-08-28 | 2000-03-09 | Smithkline Beecham P.L.C. | Use of 5-th receptor antagonists for the treatment of parkinson's disease |
| WO2000012073A1 (en) * | 1998-08-28 | 2000-03-09 | Smithkline Beecham P.L.C. | Use of 5ht-6 antagonists |
| WO2001016096A2 (de) * | 1999-09-01 | 2001-03-08 | Aventis Pharma Deutschland Gmbh | Verwendung von bissulfonamiden zur herstellung von medikamenten zur prophylaxe oder behandlung von hyperlipidämie |
| WO2001016094A1 (de) * | 1999-09-01 | 2001-03-08 | Aventis Pharma Deutschland Gmbh | Sulfonylcarboxamidderivate, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel |
Non-Patent Citations (4)
| Title |
|---|
| Arzneimittel-Forschung, Volume 19 (1969), No.10, Par G. REGNIER et al.: "Etudechimique et pharmacologique de nouveaux derives de la nor-Adrenaline", pages 1698-1702 * |
| Bioorganic & Medicinal Chemistry Letters, Volume 10, 2000, Methvin Isaac et al.: "6-Bicyclopiperazinyl-1-arylsulfonylindoles and 6-Bicyclopiperidinyl-1-arylsulfonylindoles Derivatives as Novel, Potent, and Selective 5-HT6 Receptor Antagonists", pages 1719-1721 * |
| J. Med. Chem. Volume 42, 1999, Steven M. Bromidge et al.: "Communications to the Editor: 5-Chloro-N-(4-methoxy-3-piperazin-1-ylphenyl)-3-methyl-2-benzothiophenesulfonamide (SB-271046): A Potent, Selective and Orally Bioavailable 5-HT6 Receptor Antagonist", pages 202-205 * |
| STN International, File CHEMCATS, Accession no. 2001:1380798, 31 May 2001, 2859-DMSO/9802946, Benzenesulfonamide, 3-(1-piperazinyl)-, CAS Registry No. 339014-58-3 * |
Also Published As
| Publication number | Publication date |
|---|---|
| NO326690B1 (no) | 2009-01-26 |
| PL366619A1 (en) | 2005-02-07 |
| CA2443724C (en) | 2009-11-03 |
| MXPA03010232A (es) | 2004-03-16 |
| IL158593A0 (en) | 2004-05-12 |
| HK1068335A1 (en) | 2005-04-29 |
| CA2443724A1 (en) | 2002-11-21 |
| US7319097B2 (en) | 2008-01-15 |
| BR0209558A (pt) | 2004-04-20 |
| JP2011016801A (ja) | 2011-01-27 |
| WO2002092585A1 (en) | 2002-11-21 |
| NZ528450A (en) | 2006-02-24 |
| IL158593A (en) | 2010-12-30 |
| JP4597480B2 (ja) | 2010-12-15 |
| US20030149019A1 (en) | 2003-08-07 |
| US20060009446A1 (en) | 2006-01-12 |
| IL194950A0 (en) | 2011-08-01 |
| KR20090092832A (ko) | 2009-09-01 |
| US6969710B2 (en) | 2005-11-29 |
| EA200301232A1 (ru) | 2004-04-29 |
| CN1329382C (zh) | 2007-08-01 |
| US20030149020A1 (en) | 2003-08-07 |
| US7566715B2 (en) | 2009-07-28 |
| NO20034996D0 (no) | 2003-11-10 |
| EP1406884A1 (en) | 2004-04-14 |
| US20050288275A1 (en) | 2005-12-29 |
| CN1531531A (zh) | 2004-09-22 |
| US7173035B2 (en) | 2007-02-06 |
| AU2002303061B2 (en) | 2009-01-29 |
| JP2004534755A (ja) | 2004-11-18 |
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