CA2542813A1 - Amidomethyl-substituted 2-(4-sulfonilamino)-3-hidroxy-3,4-dihydro-2h-chromen-6-yl-derivatives, process and drugs containing these compounds - Google Patents
Amidomethyl-substituted 2-(4-sulfonilamino)-3-hidroxy-3,4-dihydro-2h-chromen-6-yl-derivatives, process and drugs containing these compounds Download PDFInfo
- Publication number
- CA2542813A1 CA2542813A1 CA002542813A CA2542813A CA2542813A1 CA 2542813 A1 CA2542813 A1 CA 2542813A1 CA 002542813 A CA002542813 A CA 002542813A CA 2542813 A CA2542813 A CA 2542813A CA 2542813 A1 CA2542813 A1 CA 2542813A1
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- CA
- Canada
- Prior art keywords
- alkyl
- phenyl
- compounds
- optionally substituted
- hydrogen
- 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.)
- Granted
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- 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
-
- 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
-
- 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
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyrane Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The invention relates to compounds of general formula (I), wherein the meaning of R1, R2, R3, R4, R5 and R6 is given in a description, to a method for producing said compounds and to intermediate products thereof. Drugs containing the inventive compounds of formula (1) are also disclosed.
Claims (11)
1. Compounds of the general formula I, wherein R1 is C1-4-alkyl, R2 is C1-4-alkyl, R3 is phenyl which is optionally substituted 1 to 2 times by halogen, C1-4-alkyl, C1-4-alkoxy or trifluoromethyl; naphthyl or biphenyl, R4 is hydrogen; C1-6-alkyl or C3-7-cycloalkyl-C1-4-alkyl, R5 is hydrogen, and R6 is C1-6-alkyl; phenyl-C1-6-alkyl, the phenyl group of which is optionally substituted once by halogen; furyl-C1-4-alkyl or tetrahydronaphthyl, or R5 and R6, together with the nitrogen to which they are bonded, form a piperazine ring which is optionally substituted by phenyl.
2. Compounds according to Claim 1, wherein R1 and R2 are each methyl.
3. Compounds according to Claim 1, wherein R3 is optionally once-substituted phenyl.
4. Compounds according to Claim 1, wherein R4 is hydrogen, C1-6-alkyl or cyclopropyl-C1-4-alkyl.
5. Compounds according to Claim 1, wherein R6 is phenyl-C1-4-alkyl or tetrahydronaphthyl.
6. Compounds according to Claim 1, wherein in the pyran ring the carbon bearing the hydroxy substituent (C-3) is in the S configuration and the carbon bearing the nitrogen-containing substituent (C-4) is in the R configuration.
7. Compounds of Formula I according to one of the preceding claims, which are selected from the group consisting of 2-(4-{[(4-ethylphenyl)sulphonyl]amino}-3-hydroxy-2,2-dimethyl-3,4-dihydro-2H-chromen-6-yl)-N-1,2,3,4-tetrahydronaphthalen-1-yl acetamide;
2-((3S,4R)-4-{[(4-ethylphenyl)sulphonyl]amino}-3-hydroxy-2,2-dimethyl-3,4-dihydro-2H-chromen-6-yl)-N-[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]acetamide;
N-benzyl-2-{4-[[(4-ethylphenyl)sulphonyl](neopentyl)amino]-3-hydroxy-2,2-dimethyl-3,4-dihydro-2H-chromen-6-yl}acetamide;
2-{4-[[(4-ethylphenyl)sulphonyl](neopentyl)amino]-3-hydroxy-2,2-dimethyl-3,4-dihydro-2H-chromen-6-yl}-N-(2-phenylethyl)acetamide and 2-(4-{[(4-methylphenyl)sulphonyl]amino}-3-hydroxy-2,2-dimethyl-3,4-dihydro-2H-chromen-6-yl)-N-1,2,3,4-tetrahydronaphthalen-1-yl acetamide.
2-((3S,4R)-4-{[(4-ethylphenyl)sulphonyl]amino}-3-hydroxy-2,2-dimethyl-3,4-dihydro-2H-chromen-6-yl)-N-[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]acetamide;
N-benzyl-2-{4-[[(4-ethylphenyl)sulphonyl](neopentyl)amino]-3-hydroxy-2,2-dimethyl-3,4-dihydro-2H-chromen-6-yl}acetamide;
2-{4-[[(4-ethylphenyl)sulphonyl](neopentyl)amino]-3-hydroxy-2,2-dimethyl-3,4-dihydro-2H-chromen-6-yl}-N-(2-phenylethyl)acetamide and 2-(4-{[(4-methylphenyl)sulphonyl]amino}-3-hydroxy-2,2-dimethyl-3,4-dihydro-2H-chromen-6-yl)-N-1,2,3,4-tetrahydronaphthalen-1-yl acetamide.
8. Medicament, containing a pharmacologically active quantity of a compound of Formula I according to Claim 1 and conventional pharmaceutical auxiliaries and/or excipients.
9. The use of compounds of Formula I according to Claim 1 for the preparation of medicaments for the treatment of cardiovascular diseases and/or for the treatment of proliferative, chronic inflammatory and autoimmune diseases.
10. A process for the preparation of compounds of Formula I, wherein R1 is C1-4-alkyl, R2 is C1-4-alkyl, R3 is phenyl which is optionally substituted 1 to 2 times by halogen, C1-4-alkyl, C1-4-alkoxy or trifluoromethyl; naphthyl or biphenyl, R4 is hydrogen; C1-6-alkyl or C3-7-cycloalkyl-C1-4-alkyl, R5 is hydrogen, and R6 is C1-6-alkyl; phenyl-C1-4-alkyl, the phenyl group of which is optionally substituted once by halogen; furyl-C1-4-alkyl or tetrahydronaphthyl, or R5 and R6, together with the nitrogen to which they are bonded, form a piperazine ring which is optionally substituted by phenyl, characterised in that a compound of the general formula II, wherein R1, R2, R4, R5 and R6 have the above meanings, is reacted with a compound of the general formula III, X -SO~R3 III
wherein R3 has the above meaning and X is a cleavable leaving group.
wherein R3 has the above meaning and X is a cleavable leaving group.
11. Compounds of the general formula II, wherein R1 is C1_4-alkyl, R2 is C1-4-alkyl, R4 is hydrogen; C1-6-alkyl or C3-7-cycloalkyl-C1-4-alkyl, R5 is hydrogen, and R6 is C1-6-alkyl; phenyl-C1-4-alkyl, the phenyl group of which is optionally substituted once by halogen; furyl-C1-4-alkyl or tetrahydronaphthyl, or R5 and R6, together with the nitrogen to which they are bonded, form a piperazine ring which is optionally substituted by phenyl.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10348298A DE10348298A1 (en) | 2003-10-17 | 2003-10-17 | Amidomethyl-substituted 2- (4-sulfonylamino) -3-hydroxy-3,4-dihydro-2H-chromen-6-ylderivade, processes and intermediates for their preparation, and medicaments containing these compounds |
| DE10348298.9 | 2003-10-17 | ||
| PCT/EP2004/052539 WO2005037780A2 (en) | 2003-10-17 | 2004-10-14 | Amidomethyl-substituted 2-(4-sulfonilamino)-3-hidroxy-3,4-dihydro-2h-chromium-6-yl-derivatives and drugs containing said compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2542813A1 true CA2542813A1 (en) | 2005-04-28 |
| CA2542813C CA2542813C (en) | 2011-08-30 |
Family
ID=34442032
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2542813A Expired - Fee Related CA2542813C (en) | 2003-10-17 | 2004-10-14 | Amidomethyl-substituted 2-(4-sulfonilamino)-3-hidroxy-3,4-dihydro-2h-chromen-6-yl-derivatives, process and drugs containing these compounds |
Country Status (25)
| Country | Link |
|---|---|
| EP (1) | EP1678130B1 (en) |
| JP (1) | JP4791968B2 (en) |
| KR (1) | KR20060129170A (en) |
| CN (1) | CN100532375C (en) |
| AR (1) | AR046106A1 (en) |
| AT (1) | ATE405547T1 (en) |
| AU (1) | AU2004281195B2 (en) |
| BR (1) | BRPI0415523A (en) |
| CA (1) | CA2542813C (en) |
| DE (3) | DE10348298A1 (en) |
| DK (1) | DK1678130T3 (en) |
| ES (1) | ES2313126T3 (en) |
| HK (1) | HK1096960A1 (en) |
| HR (1) | HRP20080602T3 (en) |
| IL (1) | IL174950A (en) |
| MX (1) | MXPA06003958A (en) |
| NO (1) | NO20062202L (en) |
| PL (1) | PL1678130T3 (en) |
| PT (1) | PT1678130E (en) |
| RU (1) | RU2355685C2 (en) |
| SI (1) | SI1678130T1 (en) |
| TW (1) | TWI321564B (en) |
| UA (1) | UA82907C2 (en) |
| WO (1) | WO2005037780A2 (en) |
| ZA (1) | ZA200602788B (en) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1871758B1 (en) * | 2005-04-12 | 2010-08-25 | Abbott Products GmbH | Aminoalkyl-amidomethyl-substituted 2- (4-sulphonylamino) -3-hydroxy-3 , 4-dihydro-2h-cromen-6-yl derivatives and their use as potassium channel blockers |
| 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 |
| JP4943429B2 (en) * | 2005-07-22 | 2012-05-30 | メルク・シャープ・エンド・ドーム・コーポレイション | Potassium channel inhibitor |
| GB0525164D0 (en) | 2005-12-09 | 2006-01-18 | Xention Discovery Ltd | Compounds |
| GB0815781D0 (en) | 2008-08-29 | 2008-10-08 | Xention Ltd | Novel potassium channel blockers |
| GB0815782D0 (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 |
| NO3175985T3 (en) | 2011-07-01 | 2018-04-28 | ||
| JP2015504923A (en) | 2012-01-27 | 2015-02-16 | ギリアード サイエンシーズ， インコーポレイテッド | Combination therapy 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 (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CZ282172B6 (en) * | 1992-11-30 | 1997-05-14 | Smithkline Beecham Plc | Benzopyran analogs process for preparing such compounds, pharmaceutical composition containing such compounds and the use thereof |
| DE19546736A1 (en) * | 1995-12-14 | 1997-06-19 | Hoechst Ag | Substituted chromanylsulfonyl (thio) ureas, process for their preparation and their use in the manufacture of pharmaceutical preparations |
| WO2000012077A1 (en) * | 1998-09-01 | 2000-03-09 | Bristol-Myers Squibb Company | Potassium channel inhibitors and method |
| WO2000058300A1 (en) * | 1999-03-25 | 2000-10-05 | Nissan Chemical Industries, Ltd. | Chroman derivatives |
| JP2000336085A (en) * | 1999-03-25 | 2000-12-05 | Nissan Chem Ind Ltd | Chroman derivative |
| AU781365B2 (en) * | 1999-12-21 | 2005-05-19 | Icagen, Inc. | Potassium channel inhibitors |
-
2003
- 2003-10-17 DE DE10348298A patent/DE10348298A1/en not_active Withdrawn
-
2004
- 2004-10-13 AR ARP040103705A patent/AR046106A1/en not_active Application Discontinuation
- 2004-10-13 TW TW093130943A patent/TWI321564B/en not_active IP Right Cessation
- 2004-10-14 CN CNB2004800283503A patent/CN100532375C/en not_active Expired - Fee Related
- 2004-10-14 MX MXPA06003958A patent/MXPA06003958A/en active IP Right Grant
- 2004-10-14 PT PT04817204T patent/PT1678130E/en unknown
- 2004-10-14 RU RU2006116629/04A patent/RU2355685C2/en not_active IP Right Cessation
- 2004-10-14 DE DE112004001659T patent/DE112004001659D2/en not_active Expired - Fee Related
- 2004-10-14 DE DE502004007916T patent/DE502004007916D1/en active Active
- 2004-10-14 DK DK04817204T patent/DK1678130T3/en active
- 2004-10-14 UA UAA200605330A patent/UA82907C2/en unknown
- 2004-10-14 WO PCT/EP2004/052539 patent/WO2005037780A2/en active IP Right Grant
- 2004-10-14 AT AT04817204T patent/ATE405547T1/en active
- 2004-10-14 SI SI200430848T patent/SI1678130T1/en unknown
- 2004-10-14 PL PL04817204T patent/PL1678130T3/en unknown
- 2004-10-14 EP EP04817204A patent/EP1678130B1/en active Active
- 2004-10-14 ZA ZA200602788A patent/ZA200602788B/en unknown
- 2004-10-14 JP JP2006534762A patent/JP4791968B2/en not_active Expired - Fee Related
- 2004-10-14 AU AU2004281195A patent/AU2004281195B2/en not_active Ceased
- 2004-10-14 CA CA2542813A patent/CA2542813C/en not_active Expired - Fee Related
- 2004-10-14 KR KR1020067006939A patent/KR20060129170A/en not_active Application Discontinuation
- 2004-10-14 ES ES04817204T patent/ES2313126T3/en active Active
- 2004-10-14 BR BRPI0415523-8A patent/BRPI0415523A/en not_active IP Right Cessation
-
2006
- 2006-04-11 IL IL174950A patent/IL174950A/en not_active IP Right Cessation
- 2006-05-16 NO NO20062202A patent/NO20062202L/en not_active Application Discontinuation
-
2007
- 2007-02-23 HK HK07102051.5A patent/HK1096960A1/en not_active IP Right Cessation
-
2008
- 2008-11-20 HR HR20080602T patent/HRP20080602T3/en unknown
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed | ||
| MKLA | Lapsed |
Effective date: 20121015 |