UA77189C2 - Benzopyran derivatives as antiarrhythmic agents - Google Patents
Benzopyran derivatives as antiarrhythmic agents Download PDFInfo
- Publication number
- UA77189C2 UA77189C2 UA2004010583A UA2004010583A UA77189C2 UA 77189 C2 UA77189 C2 UA 77189C2 UA 2004010583 A UA2004010583 A UA 2004010583A UA 2004010583 A UA2004010583 A UA 2004010583A UA 77189 C2 UA77189 C2 UA 77189C2
- Authority
- UA
- Ukraine
- Prior art keywords
- group
- alkyl group
- benzopyran
- alkyl
- pharmaceutically acceptable
- Prior art date
Links
- 150000001562 benzopyrans Chemical class 0.000 title claims abstract description 21
- 239000003416 antiarrhythmic agent Substances 0.000 title abstract description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 75
- 150000003839 salts Chemical class 0.000 claims abstract description 21
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 15
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 6
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 206010003119 arrhythmia Diseases 0.000 claims description 10
- 230000006793 arrhythmia Effects 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- 239000004480 active ingredient Substances 0.000 claims description 6
- 125000003277 amino group Chemical group 0.000 claims description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
- C07D311/68—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with nitrogen atoms directly attached in position 4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Cardiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrane Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2001190594 | 2001-06-25 | ||
| PCT/JP2002/006012 WO2003000675A1 (en) | 2001-06-25 | 2002-06-17 | Substituted benzopyran derivatives against arrhythmia |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| UA77189C2 true UA77189C2 (en) | 2006-11-15 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| UA2004010583A UA77189C2 (en) | 2001-06-25 | 2002-06-17 | Benzopyran derivatives as antiarrhythmic agents |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US7041700B2 (xx) |
| EP (1) | EP1401823B1 (xx) |
| KR (1) | KR100869897B1 (xx) |
| CN (1) | CN1279036C (xx) |
| AT (1) | ATE305930T1 (xx) |
| CA (1) | CA2450541A1 (xx) |
| CZ (1) | CZ20033469A3 (xx) |
| DE (1) | DE60206505T2 (xx) |
| HK (1) | HK1063785A1 (xx) |
| HU (1) | HUP0400362A3 (xx) |
| IL (2) | IL159218A0 (xx) |
| NO (1) | NO20035774L (xx) |
| NZ (1) | NZ529916A (xx) |
| RU (1) | RU2291867C2 (xx) |
| SK (1) | SK15782003A3 (xx) |
| UA (1) | UA77189C2 (xx) |
| WO (1) | WO2003000675A1 (xx) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0315950D0 (en) | 2003-06-11 | 2003-08-13 | Xention Discovery Ltd | Compounds |
| TWI346112B (en) | 2004-02-25 | 2011-08-01 | Nissan Chemical Ind Ltd | Benzopyran compound |
| US7647250B2 (en) * | 2004-03-08 | 2010-01-12 | Sap Ag | Method and program product for event monitoring |
| AU2005223612B2 (en) | 2004-03-23 | 2010-06-24 | Nissan Chemical Industries, Ltd. | Tricyclic benzopyran compound as anti-arrhythmic agents |
| GB0412986D0 (en) | 2004-06-10 | 2004-07-14 | Xention Discovery Ltd | Compounds |
| US7576212B2 (en) | 2004-12-09 | 2009-08-18 | Xention Limited | Thieno[2,3-B] pyridines as potassium channel inhibitors |
| US7714150B2 (en) * | 2005-04-12 | 2010-05-11 | Solvay Pharmaceuticals Gmbh | Aminoalkyl-amidomethyl-substituted 2-(4-sulphonylamino)-3-hydroxy-3,4-dihydro-2H-chroman-6-yl derivatives |
| GB0525164D0 (en) | 2005-12-09 | 2006-01-18 | Xention Discovery Ltd | Compounds |
| GB0815782D0 (en) | 2008-08-29 | 2008-10-08 | Xention Ltd | Novel potassium channel blockers |
| GB0815781D0 (en) | 2008-08-29 | 2008-10-08 | Xention Ltd | Novel potassium channel blockers |
| GB0815784D0 (en) | 2008-08-29 | 2008-10-08 | Xention Ltd | Novel potassium channel blockers |
| GB201105659D0 (en) | 2011-04-01 | 2011-05-18 | Xention Ltd | Compounds |
| NO3175985T3 (xx) | 2011-07-01 | 2018-04-28 | ||
| AR090037A1 (es) | 2011-11-15 | 2014-10-15 | Xention Ltd | Derivados de tieno y/o furo-pirimidinas y piridinas inhibidores de los canales de potasio |
| WO2013072693A1 (en) | 2011-11-15 | 2013-05-23 | Xention Limited | Thieno [2, 3 - c] pyrazoles for use as potassium channel inhibitors |
| US20150045305A1 (en) | 2012-01-27 | 2015-02-12 | Gilead Sciences, Inc. | Combination therapies using late sodium ion channel blockers and potassium ion channel blockers |
| WO2014134419A1 (en) | 2013-03-01 | 2014-09-04 | Gilead Sciences, Inc. | Use of ikach blockers for the treatment of cardiac diseases |
Family Cites Families (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES454888A1 (es) | 1976-01-27 | 1978-05-01 | Beecham Group Ltd | Un procedimiento para la preparacion de nuevos cromados. |
| JPS5657786A (en) | 1979-09-28 | 1981-05-20 | Beecham Group Ltd | Chromanol derivative* its manufacture and medicinal composition containing it |
| JPS5657785A (en) | 1979-09-28 | 1981-05-20 | Beecham Group Ltd | Chromanol derivative* its manufacture and medicinal composition containing it |
| ZM7682A1 (en) | 1981-09-25 | 1983-05-23 | Beecham Group Plc | Active compounds |
| EP0091748B1 (en) | 1982-04-08 | 1986-06-18 | Beecham Group Plc | Antihypertensive benzopyranols |
| GB8610911D0 (en) | 1986-05-03 | 1986-06-11 | Beecham Group Plc | Active compounds |
| DK691488A (da) | 1987-12-14 | 1989-06-15 | Beecham Group Plc | Hidtil ukendte forbindelser |
| US5097037A (en) | 1989-07-17 | 1992-03-17 | Nissan Chemical Industries, Ltd. | Process for the optical resolution of pyranobenzoxadiazole compounds |
| JP2876712B2 (ja) | 1989-07-17 | 1999-03-31 | 日産化学工業株式会社 | 光学活性ピラノベンゾオキサジアゾール誘導体 |
| US5095016A (en) * | 1989-08-11 | 1992-03-10 | Kaken Pharmaceutical Co., Ltd. | Benzopyran compounds, processes for their production and pharmaceutical compositions |
| ATE161538T1 (de) | 1990-03-21 | 1998-01-15 | Res Corp Technologies Inc | Chirale katalysatoren und dadurch katalysierte epoxydierungsreaktionen |
| US5276168A (en) * | 1990-06-18 | 1994-01-04 | E. R. Squibb & Sons, Inc. | Benzopyran derivatives and heterocyclic analogs thereof as antiischemic agents |
| AU651105B2 (en) * | 1990-06-18 | 1994-07-14 | E.R. Squibb & Sons, Inc. | Benzopyran derivatives and heterocyclic analogs thereof as antiischemic agents |
| US5624954A (en) * | 1991-06-13 | 1997-04-29 | Smithkline Beecham P.L.C. | Benzo- and pyridopyran derivatives having anxiolytic and anti-convulsant activity |
| JPH05301878A (ja) | 1991-08-30 | 1993-11-16 | Nissan Chem Ind Ltd | 不斉エポキシ化反応 |
| US5352814A (en) | 1991-08-30 | 1994-10-04 | Nissan Chemical Industries, Ltd. | Asymmetric epoxidation reaction |
| JP2734457B2 (ja) | 1994-02-23 | 1998-03-30 | 日産化学工業株式会社 | 不斉エポキシ化反応 |
| EP0669339B1 (en) * | 1994-02-23 | 2001-05-23 | Nissan Chemical Industries Ltd. | Asymmetric epoxidation process using optically active manganese complexes |
| DE69518322T2 (de) | 1994-06-10 | 2001-02-15 | Smithkline Beecham Plc | C-4 amid substituierte verbindungen und deren verwendung als therapeutische mittel |
| US5679706A (en) * | 1994-09-30 | 1997-10-21 | Bristol-Myers Squibb Company | Combination of a potassium channel activator and an antiarrhythmic agent |
| JP4129601B2 (ja) | 1996-07-26 | 2008-08-06 | 日産化学工業株式会社 | クロマン誘導体 |
| JPH11209366A (ja) | 1998-01-23 | 1999-08-03 | Nissan Chem Ind Ltd | クロマン誘導体及び心不全治療薬 |
| EP1109544A4 (en) * | 1998-09-01 | 2004-10-27 | Bristol Myers Squibb Co | POTASSIUM CHANNEL INHIBITORS AND THEIR METHOD OF USE |
| JP2001151767A (ja) | 1999-09-17 | 2001-06-05 | Nissan Chem Ind Ltd | ベンゾピラン誘導体 |
-
2002
- 2002-06-17 NZ NZ529916A patent/NZ529916A/en unknown
- 2002-06-17 RU RU2004101964/04A patent/RU2291867C2/ru not_active IP Right Cessation
- 2002-06-17 WO PCT/JP2002/006012 patent/WO2003000675A1/en active IP Right Grant
- 2002-06-17 SK SK1578-2003A patent/SK15782003A3/sk unknown
- 2002-06-17 HU HU0400362A patent/HUP0400362A3/hu unknown
- 2002-06-17 UA UA2004010583A patent/UA77189C2/uk unknown
- 2002-06-17 KR KR1020037016875A patent/KR100869897B1/ko not_active IP Right Cessation
- 2002-06-17 CN CNB028127161A patent/CN1279036C/zh not_active Expired - Fee Related
- 2002-06-17 US US10/479,118 patent/US7041700B2/en not_active Expired - Fee Related
- 2002-06-17 DE DE60206505T patent/DE60206505T2/de not_active Expired - Lifetime
- 2002-06-17 CA CA002450541A patent/CA2450541A1/en not_active Abandoned
- 2002-06-17 EP EP02736131A patent/EP1401823B1/en not_active Expired - Lifetime
- 2002-06-17 AT AT02736131T patent/ATE305930T1/de not_active IP Right Cessation
- 2002-06-17 IL IL15921802A patent/IL159218A0/xx unknown
- 2002-06-17 CZ CZ20033469A patent/CZ20033469A3/cs unknown
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2003
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- 2003-12-22 NO NO20035774A patent/NO20035774L/no unknown
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Also Published As
| Publication number | Publication date |
|---|---|
| WO2003000675A1 (en) | 2003-01-03 |
| KR100869897B1 (ko) | 2008-11-24 |
| NO20035774L (no) | 2004-02-25 |
| IL159218A (en) | 2009-12-24 |
| SK15782003A3 (sk) | 2004-05-04 |
| IL159218A0 (en) | 2004-06-01 |
| ATE305930T1 (de) | 2005-10-15 |
| CA2450541A1 (en) | 2003-01-03 |
| US20040152763A1 (en) | 2004-08-05 |
| CZ20033469A3 (cs) | 2004-04-14 |
| KR20040018391A (ko) | 2004-03-03 |
| EP1401823B1 (en) | 2005-10-05 |
| RU2291867C2 (ru) | 2007-01-20 |
| US7041700B2 (en) | 2006-05-09 |
| HUP0400362A2 (hu) | 2004-08-30 |
| HUP0400362A3 (en) | 2007-05-29 |
| DE60206505D1 (de) | 2006-02-16 |
| EP1401823A1 (en) | 2004-03-31 |
| CN1520406A (zh) | 2004-08-11 |
| HK1063785A1 (en) | 2005-01-14 |
| CN1279036C (zh) | 2006-10-11 |
| NZ529916A (en) | 2005-04-29 |
| DE60206505T2 (de) | 2006-07-06 |
| RU2004101964A (ru) | 2005-03-27 |
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