AU665775B2 - Hypoglycemic thiazolidinediones and intermediates - Google Patents
Hypoglycemic thiazolidinediones and intermediatesInfo
- Publication number
- AU665775B2 AU665775B2 AU22973/92A AU2297392A AU665775B2 AU 665775 B2 AU665775 B2 AU 665775B2 AU 22973/92 A AU22973/92 A AU 22973/92A AU 2297392 A AU2297392 A AU 2297392A AU 665775 B2 AU665775 B2 AU 665775B2
- Authority
- AU
- Australia
- Prior art keywords
- compound
- formula
- enantiomer
- blood glucose
- substantially free
- 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.)
- Ceased
Links
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- 125000002346 iodo group Chemical group I* 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
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- BDOLXPFAFMNDOK-UHFFFAOYSA-N oxazaborolidine Chemical compound B1CCON1 BDOLXPFAFMNDOK-UHFFFAOYSA-N 0.000 description 1
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- 235000019371 penicillin G benzathine Nutrition 0.000 description 1
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- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- ICFJFFQQTFMIBG-UHFFFAOYSA-N phenformin Chemical compound NC(=N)NC(=N)NCCC1=CC=CC=C1 ICFJFFQQTFMIBG-UHFFFAOYSA-N 0.000 description 1
- 229960003243 phenformin Drugs 0.000 description 1
- 125000003884 phenylalkyl group Chemical group 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
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- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
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- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
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- 239000011775 sodium fluoride Substances 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 125000005504 styryl group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000011285 therapeutic regimen Methods 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 229960002277 tolazamide Drugs 0.000 description 1
- OUDSBRTVNLOZBN-UHFFFAOYSA-N tolazamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1CCCCCC1 OUDSBRTVNLOZBN-UHFFFAOYSA-N 0.000 description 1
- 229960005371 tolbutamide Drugs 0.000 description 1
- 125000005490 tosylate group Chemical class 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing aromatic rings
-
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/32—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- 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
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Thiazole And Isothizaole Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US73377191A | 1991-07-22 | 1991-07-22 | |
| US733771 | 1991-07-22 | ||
| PCT/US1992/005436 WO1993002079A1 (en) | 1991-07-22 | 1992-07-01 | Hypoglycemic thiazolidinediones and intermediates |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2297392A AU2297392A (en) | 1993-02-23 |
| AU665775B2 true AU665775B2 (en) | 1996-01-18 |
Family
ID=24949048
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU22973/92A Ceased AU665775B2 (en) | 1991-07-22 | 1992-07-01 | Hypoglycemic thiazolidinediones and intermediates |
Country Status (19)
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0595868B1 (en) * | 1991-07-22 | 1998-11-25 | Pfizer Inc. | Process for the preparation of (s)-4-[3-(5-methyl-2-phenyl-4-oxazolyl)- 1-hydroxypropyl]bromobenzene |
| GB9308487D0 (en) * | 1993-04-23 | 1993-06-09 | Smithkline Beecham Plc | Novel compounds |
| NZ501163A (en) | 1997-06-18 | 2002-02-01 | Smithkline Beecham P | Treatment of diabetes with thiazolidinedione and sulphonylurea (glibenclamide, glipizide, gliclazide, glimepiride, tolazamide and tolbutamide |
| TR200101333T2 (tr) * | 1998-11-12 | 2001-10-22 | Smithkline Beecham P.L.C. | Bir ensülin sensitizörü ve başka bir anti-diyabetik maddenin değiştirilmiş salımı için farmasötik terkip. |
| AR023700A1 (es) | 1998-11-12 | 2002-09-04 | Smithkline Beecham Plc | Un procedimiento para preparar una composicion farmaceutica que comprende un sensibilizador de insulina |
| EE200100556A (et) * | 1999-04-28 | 2003-02-17 | Aventis Pharma Deutschland Gmbh | Diarüülhappe derivaat, seda sisaldav farmatseutiline kompositsioon ja ühendi kasutamine ravimite valmistamiseks |
| TW200514783A (en) * | 1999-09-22 | 2005-05-01 | Bristol Myers Squibb Co | Substituted acid derivatives useful as antiodiabetic and antiobesity agents and method |
| EP1457490A1 (en) * | 1999-11-10 | 2004-09-15 | Takeda Chemical Industries, Ltd. | 5-membered N-heterocyclic compounds with hypoglycemic and hypolipidemic activity |
| KR100545507B1 (ko) * | 2000-05-26 | 2006-01-24 | 니뽄 신야쿠 가부시키가이샤 | 복소환 유도체 |
| GB0014969D0 (en) | 2000-06-19 | 2000-08-09 | Smithkline Beecham Plc | Novel method of treatment |
| JP2003040877A (ja) * | 2001-07-24 | 2003-02-13 | Sumika Fine Chemicals Co Ltd | ５−［６−（２−フルオロベンジルオキシ）−２−ナフチル］メチル−２，４−チアゾリジンジオンの製造方法及びその精製方法 |
| CN100402026C (zh) * | 2002-06-03 | 2008-07-16 | 诺瓦提斯公司 | 取代的氰基吡咯烷和含有它们的组合制剂用于治疗高脂血症和相关疾病的用途 |
| JP4290648B2 (ja) * | 2002-07-03 | 2009-07-08 | エフ．ホフマン−ラ ロシュ アーゲー | オキサゾール誘導体及びインスリン感作物質としてのそれらの使用 |
| US8216609B2 (en) | 2002-08-05 | 2012-07-10 | Torrent Pharmaceuticals Limited | Modified release composition of highly soluble drugs |
| US8268352B2 (en) | 2002-08-05 | 2012-09-18 | Torrent Pharmaceuticals Limited | Modified release composition for highly soluble drugs |
| US7560475B2 (en) * | 2003-09-22 | 2009-07-14 | Ono Pharmaceutical Co., Ltd. | Phenylacetic acid derivative, process for producing the same, and use |
| EP1586573B1 (en) * | 2004-04-01 | 2007-02-07 | Sanofi-Aventis Deutschland GmbH | Oxadiazolones, processes for their preparation and their use as pharmaceuticals |
| US20120094959A1 (en) | 2010-10-19 | 2012-04-19 | Bonnie Blazer-Yost | Treatment of cystic diseases |
| US10034868B2 (en) | 2014-11-04 | 2018-07-31 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for the prevention and the treatment of rapidly progressive glomerulonephritis |
| CN109867765A (zh) * | 2019-02-28 | 2019-06-11 | 中山大学惠州研究院 | 一种长效缓释可降解防污聚氨酯及其制备方法 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU1317788A (en) * | 1987-03-18 | 1988-09-22 | Tanabe Seiyaku Co., Ltd. | Benzoxazole derivatives and preparation thereof |
| AU1767588A (en) * | 1987-06-13 | 1988-12-15 | Beecham Group Plc | Novel compounds |
| AU593754B2 (en) * | 1988-03-08 | 1990-02-15 | Pfizer Inc. | Hypoglycemic thiazolidinedione derivatives |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5522636A (en) | 1978-08-04 | 1980-02-18 | Takeda Chem Ind Ltd | Thiazoliding derivative |
| US4367234A (en) | 1980-07-28 | 1983-01-04 | Pfizer Inc. | Hypoglycemic 5-substituted oxazolidine-2,4-diones |
| US4342771A (en) | 1981-01-02 | 1982-08-03 | Pfizer Inc. | Hypoglycemic 5-substituted oxazolidine-2,4-diones |
| US4617312A (en) | 1983-01-17 | 1986-10-14 | Pfizer Inc. | Aldose reductase inhibiting 5-(2-alkoxyphenyl) thiazolidinediones |
| CN1003445B (zh) | 1984-10-03 | 1989-03-01 | 武田药品工业株式会社 | 噻唑烷二酮衍生物，其制备方法和用途 |
| WO1986007056A1 (en) | 1985-05-21 | 1986-12-04 | Pfizer Inc. | Hypoglycemic thiazolidinediones |
| US5036079A (en) | 1989-12-07 | 1991-07-30 | Pfizer Inc. | Hypoglycemic thiazolidinedione derivatives |
| US5089514A (en) | 1990-06-14 | 1992-02-18 | Pfizer Inc. | 3-coxazolyl [phenyl, chromanyl or benzofuranyl]-2-hydroxypropionic acid derivatives and analogs as hypoglycemic agents |
-
1992
- 1992-06-30 TW TW081105174A patent/TW222626B/zh active
- 1992-07-01 BR BR9206293A patent/BR9206293A/pt not_active Application Discontinuation
- 1992-07-01 CZ CS94124A patent/CZ282831B6/cs not_active IP Right Cessation
- 1992-07-01 JP JP5502812A patent/JPH08823B2/ja not_active Expired - Fee Related
- 1992-07-01 CA CA002111447A patent/CA2111447C/en not_active Expired - Fee Related
- 1992-07-01 HU HU9400181A patent/HUT69692A/hu unknown
- 1992-07-01 RU RU94012853/04A patent/RU2079497C1/ru not_active IP Right Cessation
- 1992-07-01 WO PCT/US1992/005436 patent/WO1993002079A1/en not_active Application Discontinuation
- 1992-07-01 AU AU22973/92A patent/AU665775B2/en not_active Ceased
- 1992-07-01 EP EP92915346A patent/EP0641338A1/en not_active Withdrawn
- 1992-07-20 PT PT100711A patent/PT100711B/pt active IP Right Grant
- 1992-07-21 MX MX9204279A patent/MX9204279A/es not_active IP Right Cessation
- 1992-07-21 ZA ZA925468A patent/ZA925468B/xx unknown
- 1992-07-21 IE IE235792A patent/IE922357A1/en not_active Application Discontinuation
- 1992-07-21 IL IL102573A patent/IL102573A/xx not_active IP Right Cessation
- 1992-07-21 NZ NZ243653A patent/NZ243653A/en unknown
- 1992-07-21 CN CN92108662A patent/CN1030195C/zh not_active Expired - Fee Related
-
1994
- 1994-01-21 NO NO940225A patent/NO301226B1/no unknown
-
1995
- 1995-06-01 US US08/458,071 patent/US6329408B1/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU1317788A (en) * | 1987-03-18 | 1988-09-22 | Tanabe Seiyaku Co., Ltd. | Benzoxazole derivatives and preparation thereof |
| AU1767588A (en) * | 1987-06-13 | 1988-12-15 | Beecham Group Plc | Novel compounds |
| AU593754B2 (en) * | 1988-03-08 | 1990-02-15 | Pfizer Inc. | Hypoglycemic thiazolidinedione derivatives |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1068823A (zh) | 1993-02-10 |
| IL102573A0 (en) | 1993-01-14 |
| IL102573A (en) | 1997-04-15 |
| CA2111447A1 (en) | 1993-02-04 |
| US6329408B1 (en) | 2001-12-11 |
| NO301226B1 (no) | 1997-09-29 |
| JPH08823B2 (ja) | 1996-01-10 |
| TW222626B (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1994-04-21 |
| CN1030195C (zh) | 1995-11-01 |
| JPH07502487A (ja) | 1995-03-16 |
| CA2111447C (en) | 2002-08-13 |
| NO940225D0 (no) | 1994-01-21 |
| EP0641338A1 (en) | 1995-03-08 |
| AU2297392A (en) | 1993-02-23 |
| PT100711B (pt) | 1999-07-30 |
| CZ12494A3 (en) | 1994-07-13 |
| WO1993002079A1 (en) | 1993-02-04 |
| HU9400181D0 (en) | 1994-05-30 |
| IE922357A1 (en) | 1993-01-27 |
| BR9206293A (pt) | 1994-11-08 |
| MX9204279A (es) | 1994-03-31 |
| ZA925468B (en) | 1994-01-21 |
| NO940225L (no) | 1994-01-21 |
| PT100711A (pt) | 1993-09-30 |
| NZ243653A (en) | 1995-02-24 |
| HUT69692A (en) | 1995-09-28 |
| CZ282831B6 (cs) | 1997-10-15 |
| RU2079497C1 (ru) | 1997-05-20 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |