TWI283660B - Benzene tricarboxylic acid derivatives as insulin receptor activators - Google Patents
Benzene tricarboxylic acid derivatives as insulin receptor activators Download PDFInfo
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- TWI283660B TWI283660B TW090122095A TW90122095A TWI283660B TW I283660 B TWI283660 B TW I283660B TW 090122095 A TW090122095 A TW 090122095A TW 90122095 A TW90122095 A TW 90122095A TW I283660 B TWI283660 B TW I283660B
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- compound
- substituted
- group
- naphthyl
- phenyl
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- 102000003746 Insulin Receptor Human genes 0.000 title abstract description 54
- 108010001127 Insulin Receptor Proteins 0.000 title abstract description 54
- UJMDYLWCYJJYMO-UHFFFAOYSA-N benzene-1,2,3-tricarboxylic acid Chemical class OC(=O)C1=CC=CC(C(O)=O)=C1C(O)=O UJMDYLWCYJJYMO-UHFFFAOYSA-N 0.000 title description 2
- 239000012190 activator Substances 0.000 title 1
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- 125000000217 alkyl group Chemical group 0.000 claims description 127
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- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 15
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- 125000004093 cyano group Chemical group *C#N 0.000 claims description 13
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- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 claims description 9
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Classifications
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- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
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- 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
- A61P3/08—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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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
- C07C233/81—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/01—Sulfonic acids
- C07C309/28—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C309/45—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing nitrogen atoms, not being part of nitro or nitroso groups, bound to the carbon skeleton
- C07C309/51—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing nitrogen atoms, not being part of nitro or nitroso groups, bound to the carbon skeleton at least one of the nitrogen atoms being part of any of the groups, X being a hetero atom, Y being any atom
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/566—Immunoassay; Biospecific binding assay; Materials therefor using specific carrier or receptor proteins as ligand binding reagents where possible specific carrier or receptor proteins are classified with their target compounds
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/90—Enzymes; Proenzymes
- G01N2333/91—Transferases (2.)
- G01N2333/912—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/04—Endocrine or metabolic disorders
- G01N2800/042—Disorders of carbohydrate metabolism, e.g. diabetes, glucose metabolism
Landscapes
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- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
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- Immunology (AREA)
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- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
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- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US23073800P | 2000-09-07 | 2000-09-07 |
Publications (1)
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|---|---|
| TWI283660B true TWI283660B (en) | 2007-07-11 |
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|---|---|---|---|
| TW090122095A TWI283660B (en) | 2000-09-07 | 2001-09-06 | Benzene tricarboxylic acid derivatives as insulin receptor activators |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US6600069B2 (https=) |
| EP (1) | EP1315695B1 (https=) |
| JP (1) | JP2004508348A (https=) |
| AR (1) | AR030620A1 (https=) |
| AT (1) | ATE299491T1 (https=) |
| AU (1) | AU8889101A (https=) |
| CA (1) | CA2421581A1 (https=) |
| DE (1) | DE60111948T2 (https=) |
| DK (1) | DK1315695T3 (https=) |
| ES (1) | ES2241867T3 (https=) |
| TW (1) | TWI283660B (https=) |
| WO (1) | WO2002020464A2 (https=) |
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|---|---|---|---|---|
| IT1391474B1 (it) * | 2008-10-02 | 2011-12-23 | Università Degli Studi Di Roma La Sapienza | Derivati carbonilici a simmetria c3, loro preparazione e loro uso |
| KR101121954B1 (ko) | 2010-05-13 | 2012-03-09 | 아주대학교산학협력단 | 1,2,3-Benzentricarboxylic acid를 유효성분으로 포함하는 당뇨병 예방 또는 치료용 조성물 |
| JP6255210B2 (ja) * | 2013-10-24 | 2017-12-27 | アーゼッド・エレクトロニック・マテリアルズ(ルクセンブルグ)ソシエテ・ア・レスポンサビリテ・リミテ | レジスト下層膜形成組成物 |
| US20220288068A1 (en) * | 2019-07-10 | 2022-09-15 | Merck Patent Gmbh | Pharmaceutical preparation |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4051176A (en) | 1976-05-10 | 1977-09-27 | American Cyanamid Company | Ureidophenylenebis(carbonylimino)dinaphthalenetrisulfonic acid compounds |
| US4046805A (en) | 1976-05-10 | 1977-09-06 | American Cyanamid Company | Substituted-hydroxy-naphthalenedisulfonic acid compounds |
| US4129591A (en) | 1976-10-27 | 1978-12-12 | American Cyanamid Company | Ureida-phenylenebis(substituted imino)multianionic substituted dinaphthalene sulfonic acids and salts |
| US4102917A (en) | 1977-06-01 | 1978-07-25 | American Cyanamid Company | Substituted phenyl naphthalenesulfonic acids |
| US4123455A (en) | 1977-06-13 | 1978-10-31 | American Cyanamid Company | Phenenyltris(carbonylimino) multi-anionic substituted triphenyl acids and salts |
| US4089974A (en) | 1977-06-13 | 1978-05-16 | American Cyanamid Company | 5-Carboxy-phenylenebis(carbonylimino)benzene carboxylic and dicarboxylic acids and salts |
| US4120895A (en) | 1977-06-29 | 1978-10-17 | American Cyanamid Company | S-phenenyltris (iminocarbonyl) triisophthalic acid salts |
| US4132730A (en) | 1977-07-29 | 1979-01-02 | American Cyanamid Company | Ureylene naphthalene sulfonic acids |
| US4120891A (en) | 1977-07-01 | 1978-10-17 | American Cyanamid Company | Ureylene naphthalene sulfonic acids |
| US4118585A (en) | 1977-07-01 | 1978-10-03 | American Cyanamid Company | Anionic benzene tetrakis carbonylimino isophthalic acid salts |
| US4229371A (en) * | 1977-07-29 | 1980-10-21 | American Cyanamid Company | Ureylene naphthalene sulfonic acid intermediates |
| CH654853A5 (de) | 1982-08-07 | 1986-03-14 | Sandoz Ag | Verfahren zum verdichten von anodisch oxydierten aluminiumoberflaechen. |
| DE4229182A1 (de) | 1992-09-02 | 1994-03-03 | Basf Ag | Metallchelate |
| US5599984A (en) | 1994-01-21 | 1997-02-04 | The Picower Institute For Medical Research | Guanylhydrazones and their use to treat inflammatory conditions |
| US5973076A (en) | 1995-05-31 | 1999-10-26 | New Japan Chemical Co., Ltd. | Polybutene-1 resin composition and a method of accelerating the crystal transformation thereof |
| US5565432A (en) * | 1994-11-07 | 1996-10-15 | American Home Products Corporation | Smooth muscle cell proliferation inhibitors |
| TR199600329A2 (tr) | 1995-05-05 | 1997-03-21 | Hoffmann La Roche | Seker alkollerin yeni sülfürik asit esterleri. |
| JPH08333324A (ja) * | 1995-06-08 | 1996-12-17 | Terumo Corp | ベンゼン誘導体およびそれを含有する医薬製剤 |
| JP3836910B2 (ja) * | 1996-01-19 | 2006-10-25 | 富士写真フイルム株式会社 | ハロゲン化銀写真感光材料およびその処理方法 |
| EP1277790A3 (en) | 1998-03-04 | 2004-07-28 | Ciba SC Holding AG | Nucleators for crystallizable thermoplastic polymers |
| IL147032A0 (en) | 1999-07-29 | 2002-08-14 | Telik Inc | Novel naphthylsulfonic acids and related compounds as glucose uptake agonists |
-
2001
- 2001-09-06 CA CA002421581A patent/CA2421581A1/en not_active Abandoned
- 2001-09-06 EP EP01968657A patent/EP1315695B1/en not_active Expired - Lifetime
- 2001-09-06 AT AT01968657T patent/ATE299491T1/de not_active IP Right Cessation
- 2001-09-06 AU AU8889101A patent/AU8889101A/xx not_active Withdrawn
- 2001-09-06 DE DE60111948T patent/DE60111948T2/de not_active Expired - Fee Related
- 2001-09-06 DK DK01968657T patent/DK1315695T3/da active
- 2001-09-06 ES ES01968657T patent/ES2241867T3/es not_active Expired - Lifetime
- 2001-09-06 JP JP2002525087A patent/JP2004508348A/ja not_active Withdrawn
- 2001-09-06 TW TW090122095A patent/TWI283660B/zh not_active IP Right Cessation
- 2001-09-06 US US09/949,165 patent/US6600069B2/en not_active Expired - Fee Related
- 2001-09-06 WO PCT/US2001/028084 patent/WO2002020464A2/en not_active Ceased
- 2001-09-06 AR ARP010104240A patent/AR030620A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AU8889101A (en) | 2002-03-22 |
| ES2241867T3 (es) | 2005-11-01 |
| US20020103183A1 (en) | 2002-08-01 |
| DK1315695T3 (da) | 2005-08-08 |
| WO2002020464A8 (en) | 2003-07-10 |
| WO2002020464A3 (en) | 2002-06-20 |
| DE60111948D1 (de) | 2005-08-18 |
| EP1315695A2 (en) | 2003-06-04 |
| CA2421581A1 (en) | 2002-03-14 |
| JP2004508348A (ja) | 2004-03-18 |
| DE60111948T2 (de) | 2006-04-20 |
| US6600069B2 (en) | 2003-07-29 |
| ATE299491T1 (de) | 2005-07-15 |
| WO2002020464A2 (en) | 2002-03-14 |
| EP1315695B1 (en) | 2005-07-13 |
| AR030620A1 (es) | 2003-08-27 |
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Legal Events
| Date | Code | Title | Description |
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| MM4A | Annulment or lapse of patent due to non-payment of fees |