MX2011000051A - Nuevos compuestos, composiciones farmaceuticas que contienen los mismos, metodos para usar los mismos, y metodos para preparar los mismos. - Google Patents
Nuevos compuestos, composiciones farmaceuticas que contienen los mismos, metodos para usar los mismos, y metodos para preparar los mismos.Info
- Publication number
- MX2011000051A MX2011000051A MX2011000051A MX2011000051A MX2011000051A MX 2011000051 A MX2011000051 A MX 2011000051A MX 2011000051 A MX2011000051 A MX 2011000051A MX 2011000051 A MX2011000051 A MX 2011000051A MX 2011000051 A MX2011000051 A MX 2011000051A
- Authority
- MX
- Mexico
- Prior art keywords
- group
- compound according
- alkylaryl
- aryl
- residue
- Prior art date
Links
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
- C07C311/02—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C311/08—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
-
- 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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/18—Sulfonamides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- 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
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
- C07C311/02—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C311/03—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the sulfonamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C311/06—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the sulfonamide groups bound to hydrogen atoms or to acyclic carbon atoms to acyclic carbon atoms of hydrocarbon radicals substituted by carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
- C07C311/12—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing rings
- C07C311/13—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing rings the carbon skeleton containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
- C07C311/21—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/55—Acids; Esters
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
- C07F9/3834—Aromatic acids (P-C aromatic linkage)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
- C07F9/3882—Arylalkanephosphonic acids
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biochemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Child & Adolescent Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Pyridine Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US12957808P | 2008-07-07 | 2008-07-07 | |
| PCT/US2009/049744 WO2010005922A1 (en) | 2008-07-07 | 2009-07-07 | Novel compounds, pharmaceutical compositions containing same, methods of use for same, and methods for preparing same |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MX2011000051A true MX2011000051A (es) | 2011-07-28 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2011000051A MX2011000051A (es) | 2008-07-07 | 2009-07-07 | Nuevos compuestos, composiciones farmaceuticas que contienen los mismos, metodos para usar los mismos, y metodos para preparar los mismos. |
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| Country | Link |
|---|---|
| US (1) | US20120083471A1 (enExample) |
| EP (1) | EP2303013A1 (enExample) |
| JP (1) | JP2011527345A (enExample) |
| CN (1) | CN102395270B (enExample) |
| CA (1) | CA2729767A1 (enExample) |
| MX (1) | MX2011000051A (enExample) |
| WO (1) | WO2010005922A1 (enExample) |
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| UA103319C2 (en) | 2008-05-06 | 2013-10-10 | Глаксосмитклайн Ллк | Thiazole- and oxazole-benzene sulfonamide compounds |
| JP2013532688A (ja) | 2010-07-26 | 2013-08-19 | ブリストル−マイヤーズ スクイブ カンパニー | Ｃｙｐ１７阻害剤として有用なスルホンアミド化合物 |
| CN103380115B (zh) * | 2010-12-16 | 2016-08-24 | 阿勒根公司 | 作为趋化因子受体调节剂的硫衍生物 |
| EP2687507B1 (en) * | 2011-03-14 | 2016-03-09 | Taisho Pharmaceutical Co., Ltd. | Nitrogen-containing condensed heterocyclic compound |
| EP2567959B1 (en) | 2011-09-12 | 2014-04-16 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| WO2013155528A2 (en) * | 2012-04-13 | 2013-10-17 | Fasgen, Inc. | Methods for reducing brain inflammation, increasing insulin sensitivity, and reducing ceramide levels |
| BR112016014180A2 (pt) | 2013-12-18 | 2017-09-26 | Astex Therapeutics Ltd | reguladores de nrf2 |
| US9701627B2 (en) * | 2014-06-16 | 2017-07-11 | University Of Maryland, Baltimore | LRRK2 GTP binding inhibitors for treatment of Parkinson's disease and neuroinflammatory disorders |
| WO2016172218A1 (en) * | 2015-04-20 | 2016-10-27 | The Regents Of The University Of Michigan | Small molecule inhibitors of mcl-1 and uses thereof |
| KR20180018684A (ko) | 2015-06-15 | 2018-02-21 | 글락소스미스클라인 인털렉츄얼 프로퍼티 디벨로프먼트 리미티드 | Nrf2 조절제 |
| PH12017502255B1 (en) | 2015-06-15 | 2022-07-22 | Astex Therapeutics Ltd | Nrf2 regulators |
| EP3359532A1 (en) | 2015-10-06 | 2018-08-15 | GlaxoSmithKline Intellectual Property Development Limited | Biaryl pyrazoles as nrf2 regulators |
| US11702394B2 (en) | 2018-02-23 | 2023-07-18 | The Board Of Trustees Of The Leland Stanford Junior University | Inhibitors of phospholipid synthesis and methods of use |
| WO2021035031A1 (en) * | 2019-08-21 | 2021-02-25 | The Board Of Trustees Of The Leland Stanford Junior University | Inhibitors of phospholipid synthesis and methods of use |
| AR127055A1 (es) | 2021-09-14 | 2023-12-13 | Lilly Co Eli | Sales agonistas de sstr4 |
| WO2025140544A1 (zh) * | 2023-12-28 | 2025-07-03 | 南京瑞初医药有限公司 | Gsdmd抑制剂及其用途 |
Family Cites Families (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2531367A (en) * | 1947-07-15 | 1950-11-21 | Sharp & Dohme Inc | N-(substituted sulfonyl)-aminobenzoic acids |
| DE2611705A1 (de) * | 1976-03-18 | 1977-09-22 | Josef Dipl Chem Dr Rer N Klosa | N-5-(nitrofurfuryliden-)-1-amino- hydantoin enthaltende kristalloesungsmittel |
| DE3000377A1 (de) * | 1980-01-07 | 1981-07-09 | Boehringer Mannheim Gmbh, 6800 Mannheim | Neue sulfonamide, verfahren zu deren herstellung sowie diese verbindungen enthaltende arzneimittel |
| FR2509305B1 (fr) * | 1981-07-08 | 1986-04-18 | Sanofi Sa | Benzamides, procede pour leur preparation et compositions pharmaceutiques les renfermant |
| AU567140B2 (en) * | 1984-01-06 | 1987-11-12 | Shionogi & Co., Ltd. | Sulphonamido-benzamide derivatives |
| DE4003054A1 (de) * | 1990-02-02 | 1991-08-08 | Hoechst Ag | Verwendung von benzylphosphonsaeurederivaten zur behandlung von durch viren verursachte krankheiten |
| DE69023336T2 (de) * | 1990-08-22 | 1996-05-30 | Agfa Gevaert Nv | Partikeltonermaterial. |
| JP3577336B2 (ja) * | 1994-04-26 | 2004-10-13 | 三井化学株式会社 | 感熱記録材料 |
| US5981575A (en) * | 1996-11-15 | 1999-11-09 | Johns Hopkins University, The | Inhibition of fatty acid synthase as a means to reduce adipocyte mass |
| US20030124187A1 (en) * | 1997-02-14 | 2003-07-03 | Smithkline Beecham Laboratoires Pharmaceutiques, | Pharmaceutical formulations comprising amoxycillin and clavulanate |
| JP2000006528A (ja) * | 1998-06-25 | 2000-01-11 | Fuji Photo Film Co Ltd | 感熱記録材料 |
| US6048680A (en) * | 1998-12-09 | 2000-04-11 | Eastman Kodak Company | Photographic element containing pyrazoloazole coupler and a specific anti-fading combination |
| JP2000302793A (ja) * | 1999-02-18 | 2000-10-31 | Ono Pharmaceut Co Ltd | ホスホン酸誘導体 |
| DE10121003A1 (de) * | 2001-04-28 | 2002-12-19 | Aventis Pharma Gmbh | Anthranilsäureamide, Verfahren zur Herstellung, ihrer Verwendung als Medikament sowie sie enthaltende pharmazeutische Zubereitungen |
| WO2003043624A1 (en) * | 2001-11-16 | 2003-05-30 | Bristol-Myers Squibb Company | Dual inhibitors of adipocyte fatty acid binding protein and keratinocyte fatty acid binding protein |
| US7119120B2 (en) * | 2001-12-26 | 2006-10-10 | Genzyme Corporation | Phosphate transport inhibitors |
| DK1471890T3 (da) * | 2002-02-07 | 2007-01-08 | Pharmacia Corp | Farmaceutisk doseringsform til mukös afgivelse |
| AU2003258491A1 (en) * | 2002-09-05 | 2004-03-29 | Neurosearch A/S | Amide derivatives and their use as chloride channel blockers |
| US7229966B2 (en) * | 2002-12-17 | 2007-06-12 | Nastech Pharmaceutical Company Inc. | Compositions and methods for enhanced mucosal delivery of Y2 receptor-binding peptides and methods for treating and preventing obesity |
| US20040265320A1 (en) * | 2003-01-29 | 2004-12-30 | Karl Salzwedel | Inhibition of HIV-1 replication by disruption of the processing of the viral capsid-spacer peptide 1 protein |
| DE602006003661D1 (de) * | 2005-06-06 | 2008-12-24 | Lilly Co Eli | Ampa-rezeptoren-verstärker |
| GB0526252D0 (en) * | 2005-12-22 | 2006-02-01 | Novartis Ag | Organic compounds |
| AU2007275873B2 (en) * | 2006-07-14 | 2012-06-14 | Chemocentryx, Inc. | Triazolyl phenyl benzenesulfonamides |
| WO2008020026A1 (en) * | 2006-08-16 | 2008-02-21 | Action Medicines, S.L. | Use of 2,5-dihydroxybenzene derivatives for treating dermatitis |
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2009
- 2009-07-07 MX MX2011000051A patent/MX2011000051A/es unknown
- 2009-07-07 JP JP2011517507A patent/JP2011527345A/ja active Pending
- 2009-07-07 WO PCT/US2009/049744 patent/WO2010005922A1/en not_active Ceased
- 2009-07-07 CN CN200980135092.1A patent/CN102395270B/zh not_active Expired - Fee Related
- 2009-07-07 EP EP09795032A patent/EP2303013A1/en not_active Withdrawn
- 2009-07-07 CA CA2729767A patent/CA2729767A1/en not_active Abandoned
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2011
- 2011-10-14 US US13/273,740 patent/US20120083471A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| WO2010005922A1 (en) | 2010-01-14 |
| CA2729767A1 (en) | 2010-01-14 |
| JP2011527345A (ja) | 2011-10-27 |
| CN102395270A (zh) | 2012-03-28 |
| EP2303013A1 (en) | 2011-04-06 |
| US20120083471A1 (en) | 2012-04-05 |
| CN102395270B (zh) | 2014-11-12 |
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