PL227937B1 - Sposób wytwarzania związku typu eteru aminocykloheksylowego, związek typu eteru aminocykloheksylowego, jego kompozycja, sposób modulowania aktywności kanałów jonowych, oraz zastosowanie związku typu eteru aminocykloheksylowego do wytwarzania leku - Google Patents
Sposób wytwarzania związku typu eteru aminocykloheksylowego, związek typu eteru aminocykloheksylowego, jego kompozycja, sposób modulowania aktywności kanałów jonowych, oraz zastosowanie związku typu eteru aminocykloheksylowego do wytwarzania leku Download PDFInfo
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- PL227937B1 PL227937B1 PL378918A PL37891803A PL227937B1 PL 227937 B1 PL227937 B1 PL 227937B1 PL 378918 A PL378918 A PL 378918A PL 37891803 A PL37891803 A PL 37891803A PL 227937 B1 PL227937 B1 PL 227937B1
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- Prior art keywords
- compound
- formula
- cyclohexane
- reacting
- dimethoxyphenethoxy
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/12—Oxygen or sulfur atoms
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- 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
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- 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
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pyrrole Compounds (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (15)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US46715903P | 2003-05-02 | 2003-05-02 | |
| US60/467,159 | 2003-05-02 | ||
| US47608303P | 2003-06-04 | 2003-06-04 | |
| US60/476,083 | 2003-06-04 | ||
| US47588403P | 2003-06-05 | 2003-06-05 | |
| US47591203P | 2003-06-05 | 2003-06-05 | |
| US47644703P | 2003-06-05 | 2003-06-05 | |
| US60/475,884 | 2003-06-05 | ||
| US60/475,912 | 2003-06-05 | ||
| US60/476,447 | 2003-06-05 | ||
| US48965903P | 2003-07-23 | 2003-07-23 | |
| US60/489,659 | 2003-07-23 | ||
| US49339203P | 2003-08-07 | 2003-08-07 | |
| US60/493,392 | 2003-08-07 | ||
| PCT/US2003/034655 WO2004099137A1 (en) | 2003-05-02 | 2003-10-31 | Aminocyclohexyl ether compounds and uses thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| PL378918A1 PL378918A1 (pl) | 2006-06-12 |
| PL227937B1 true PL227937B1 (pl) | 2018-01-31 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PL378918A PL227937B1 (pl) | 2003-05-02 | 2003-10-31 | Sposób wytwarzania związku typu eteru aminocykloheksylowego, związek typu eteru aminocykloheksylowego, jego kompozycja, sposób modulowania aktywności kanałów jonowych, oraz zastosowanie związku typu eteru aminocykloheksylowego do wytwarzania leku |
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|---|---|
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| EP (3) | EP2298735A1 (https=) |
| JP (2) | JP4919661B2 (https=) |
| KR (1) | KR101059379B1 (https=) |
| AT (2) | ATE325789T1 (https=) |
| AU (2) | AU2003287378B2 (https=) |
| BR (2) | BRPI0318278B8 (https=) |
| CA (1) | CA2524323C (https=) |
| CY (1) | CY1105137T1 (https=) |
| DE (1) | DE60305200T2 (https=) |
| DK (1) | DK1560812T3 (https=) |
| ES (2) | ES2264776T3 (https=) |
| IL (2) | IL171653A (https=) |
| NO (1) | NO334094B1 (https=) |
| NZ (1) | NZ543921A (https=) |
| PL (1) | PL227937B1 (https=) |
| PT (1) | PT1560812E (https=) |
| RU (1) | RU2478617C2 (https=) |
| SG (2) | SG167670A1 (https=) |
| SI (1) | SI1560812T1 (https=) |
| WO (1) | WO2004099137A1 (https=) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2326777C (en) * | 1998-04-01 | 2011-12-20 | Nortran Pharmaceuticals Inc. | Aminocyclohexyl ether compounds and uses thereof |
| US7507545B2 (en) | 1999-03-31 | 2009-03-24 | Cardiome Pharma Corp. | Ion channel modulating activity method |
| US7524879B2 (en) | 2000-10-06 | 2009-04-28 | Cardiome Pharma Corp. | Ion channel modulating compounds and uses thereof |
| US7057053B2 (en) * | 2000-10-06 | 2006-06-06 | Cardiome Pharma Corp. | Ion channel modulating compounds and uses thereof |
| US20080063707A1 (en) * | 2003-05-02 | 2008-03-13 | Cardiome Pharma Corp. | Controlled release tablet formulations for the prevention of arrhythmias |
| US7345086B2 (en) | 2003-05-02 | 2008-03-18 | Cardiome Pharma Corp. | Uses of ion channel modulating compounds |
| CA2524323C (en) * | 2003-05-02 | 2012-05-15 | Cardiome Pharma Corp. | Aminocyclohexyl ether compounds and uses thereof |
| WO2005018635A2 (en) | 2003-08-07 | 2005-03-03 | Cardiome Pharma Corp. | Ion channel modulating activity i |
| US7345087B2 (en) * | 2003-10-31 | 2008-03-18 | Cardiome Pharma Corp. | Aminocyclohexyl ether compounds and uses thereof |
| US7705036B2 (en) | 2004-04-01 | 2010-04-27 | Cardiome Pharma Corp. | Deuterated aminocyclohexyl ether compounds and processes for preparing same |
| WO2005097087A2 (en) | 2004-04-01 | 2005-10-20 | Cardiome Pharma Corp. | Merged ion channel modulating compounds and uses thereof |
| US7754897B2 (en) | 2005-06-15 | 2010-07-13 | Cardiome Pharma Corp. | Synthetic processes for the preparation of aminocyclohexyl ether compounds |
| MXPA06011419A (es) | 2004-04-01 | 2007-04-20 | Cardiome Pharma Corp | Profarmacos de compuestos moduladores de canales ionicos y usos de los mismos. |
| JP4991037B2 (ja) * | 2004-04-01 | 2012-08-01 | カーディオム ファーマ コーポレイション | イオンチャネル調節化合物を含む薬物結合体 |
| ES2483940T3 (es) * | 2004-11-08 | 2014-08-08 | Cardiome Pharma Corp. | Un nuevo régimen de dosificación para compuestos moduladores del canal iónico para el tratamiento de la fibrilación auricular aguda en un ser humano |
| EP1828099B1 (en) | 2004-11-18 | 2020-01-22 | Correvio International Sàrl | Synthetic process for aminocyclohexyl ether compounds |
| WO2006075778A1 (en) * | 2005-01-12 | 2006-07-20 | Astellas Pharma Inc. | Production method of optically active cyclohexane ether compounds |
| JP4167297B2 (ja) | 2005-08-23 | 2008-10-15 | 株式会社カネカ | ３−アラルキルオキシピロリジン誘導体の製造法 |
| CA2627502C (en) * | 2005-10-31 | 2014-04-01 | Toray Fine Chemicals Co., Ltd. | Process for production of benzyloxypyrrolidine derivative, and process for production of hydrochloride salt powder of optically active benzyloxypyrrolidine derivative |
| JP5004073B2 (ja) * | 2006-06-13 | 2012-08-22 | 東レ・ファインケミカル株式会社 | 光学活性ベンジルオキシピロリジン誘導体塩酸塩粉体及びその製造法 |
| JP5004067B2 (ja) * | 2005-10-31 | 2012-08-22 | 東レ・ファインケミカル株式会社 | ベンジルオキシ含窒素環状化合物の製造法 |
| JP2007131597A (ja) * | 2005-11-11 | 2007-05-31 | Toray Fine Chemicals Co Ltd | ベンジルオキシピロリジン誘導体の製造方法 |
| WO2008137778A2 (en) * | 2007-05-04 | 2008-11-13 | Cardiome Pharma Corp. | Controlled release oral formulations of ion channel modulating compounds and related methods for preventing arrhythmia |
| US8932836B2 (en) | 2010-08-16 | 2015-01-13 | Codexis, Inc. | Biocatalysts and methods for the synthesis of (1R,2R)-2-(3,4-dimethoxyphenethoxy)cyclohexanamine |
| WO2012024100A2 (en) | 2010-08-16 | 2012-02-23 | Merck Sharp & Dohme Corp. | Process for preparing aminocyclohexyl ether compounds |
| JP6615865B2 (ja) * | 2014-08-01 | 2019-12-04 | コベストロ、ドイチュラント、アクチエンゲゼルシャフト | 環状および直鎖状オリゴマーならびに改善した光学特性を有するコポリカーボネート組成物 |
Family Cites Families (67)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2954380A (en) * | 1958-11-26 | 1960-09-27 | Us Vitamin Pharm Corp | Piperazinocyclohexyl esters |
| US3218328A (en) * | 1963-02-18 | 1965-11-16 | U S Vitamin & Pharmacentical C | Heterocyclic amino phenoxyacetic acids, acid addition salts and quaternary ammonium salts thereof |
| DE2259260A1 (de) | 1972-12-04 | 1974-06-06 | Merck Patent Gmbh | Neue amine |
| US4179501A (en) * | 1976-11-12 | 1979-12-18 | The Upjohn Company | Analgesic N-(2-aminocycloaliphatic)azidobenzamides |
| US4145435A (en) * | 1976-11-12 | 1979-03-20 | The Upjohn Company | 2-aminocycloaliphatic amide compounds |
| DE2658401A1 (de) | 1976-12-23 | 1978-07-06 | Merck Patent Gmbh | Cyclopentan-1-amine, verfahren zu ihrer herstellung und diese verbindungen enthaltende mittel |
| US4656182A (en) * | 1983-12-06 | 1987-04-07 | Warner-Lambert Company | Substituted trans-1,2-diaminocyclohexyl amide compounds |
| US4598087A (en) | 1983-12-06 | 1986-07-01 | Warner-Lambert Company | Substituted trans-1,2-diaminocyclohexyl amide compounds |
| NL8501429A (nl) | 1984-05-18 | 1985-12-16 | Glaxo Group Ltd | Aminocyclopentylethers, hun bereiding en farmaceutische preparaten ervan. |
| US4663343A (en) * | 1985-07-19 | 1987-05-05 | Warner-Lambert Company | Substituted naphthalenyloxy-1,2-diaminocyclohexyl amide compounds |
| EP0222533A1 (en) | 1985-10-25 | 1987-05-20 | The Upjohn Company | Cis-N-[(2-aminocycloaliphatic)benzene acetamide and -benzamide anticonvulsants |
| US5059620A (en) * | 1985-12-27 | 1991-10-22 | The Du Pont Merck Pharmaceutical Company | Aryl substituted aminomethyl benzene derivatives |
| US4855316A (en) * | 1988-02-18 | 1989-08-08 | Warner-Lambert Company | 1,2-diamino-4,5-dimethoxycyclohexyl amide analgesic compounds |
| AU626949B2 (en) | 1988-12-06 | 1992-08-13 | Warner-Lambert Company | 2-amino-4 or 5-methoxycyclohexyl amides useful as analgesics |
| US5051428A (en) * | 1988-12-06 | 1991-09-24 | Warner-Lambert Company | 2-amino-4 or 5-methoxycyclohexyl amides useful as analgesics |
| US4906655A (en) * | 1989-01-24 | 1990-03-06 | Warner-Lambert Company | Novel 1,2-cyclohexylaminoaryl amides useful as analgesic agents |
| JPH02270864A (ja) | 1989-04-12 | 1990-11-05 | Asahi Glass Co Ltd | フルオロカルバサイクリックヌクレオシドおよびその製造法 |
| US5428031A (en) | 1991-12-03 | 1995-06-27 | Merck & Co., Inc. | Methods of treating cardiac arrhythmia |
| ZA929008B (en) | 1991-12-13 | 1993-05-21 | Bristol Myers Squibb Co | Piperazinyl- and piperidinyl-cyclohexanols. |
| CA2058502A1 (en) | 1991-12-27 | 1993-06-28 | David C. Horwell | 2-amino-mono-methoxycyclohexyl amides useful as analgesics |
| EP0552386A1 (en) | 1992-01-13 | 1993-07-28 | Warner-Lambert Company | 2-Amino-3 or 6-methoxycyclohexyl amide derivatives |
| JP3190676B2 (ja) | 1992-03-26 | 2001-07-23 | ザ ユニバーシティー オブ ブリティッシュ コロンビア | アミノシクロヘキシルアミド類を含有する抗不整脈及び麻酔剤 |
| US5506257A (en) * | 1992-03-26 | 1996-04-09 | University Of British Columbia | Aminocyclohexylamides for antiarrhythmic and anaesthetic uses |
| GB9220286D0 (en) | 1992-09-25 | 1992-11-11 | Merck Sharp & Dohme | Therapeutic agents |
| US5451596A (en) | 1992-12-29 | 1995-09-19 | Rhone Poulenc Rorer Pharmaceuticals Inc. | Cycloalkyl amine bis-aryl squalene synthase inhibitors |
| US5747278A (en) * | 1993-05-21 | 1998-05-05 | California Institute Of Technology | DNA encoding inward rectifier, G-protein activated, mammalian, potassium KGA channel and uses thereof |
| US5492825A (en) * | 1993-08-06 | 1996-02-20 | The Regents Of The University Of California | Mammalian inward rectifier potassium channel cDNA, IRK1, corresponding vectors, and transformed cells |
| DE69429524T2 (de) * | 1993-09-24 | 2002-08-08 | The University Of British Columbia, Vancouver | Aminocyclohexylester und ihre anwendung |
| GB9406043D0 (en) * | 1994-03-26 | 1994-05-18 | Smithkline Beecham Plc | Compounds |
| US5441946A (en) | 1994-04-14 | 1995-08-15 | Rhone-Poulenc-Rorer Pharmaceuticals, Inc. | Phosphonate derivatives of lipophilic amines |
| JPH10503768A (ja) * | 1994-08-02 | 1998-04-07 | メルク シヤープ エンド ドーム リミテツド | アゼチジン、ピロリジンおよびピペリジン誘導体 |
| AU3354895A (en) * | 1994-09-19 | 1996-04-09 | Fujisawa Pharmaceutical Co., Ltd. | Novel medicinal use of 5ht3 antagonist |
| US5556990A (en) | 1994-12-16 | 1996-09-17 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Polyarylcarbamoylaza- and -carbamoylalkanedioic acids |
| US6214608B1 (en) | 1995-02-03 | 2001-04-10 | Basf Aktiengesellschaft | Resolution of racemates of primary and secondary heteroatom-substitued amines by enzyme-catalyzed acylation |
| DK0876140T3 (da) | 1996-01-25 | 2003-12-15 | Schering Ag | Forbedrede kontrastmiddelopløsninger til intravasal anvendelse |
| US5763445A (en) | 1996-03-08 | 1998-06-09 | Adolor Corporation | Kappa agonist compounds pharmaceutical formulations and method of prevention and treatment of pruritus therewith |
| US5646151A (en) | 1996-03-08 | 1997-07-08 | Adolor Corporation | Kappa agonist compounds and pharmaceutical formulations thereof |
| JP2000514049A (ja) | 1996-06-27 | 2000-10-24 | スミスクライン・ビーチャム・コーポレイション | Ｉｌ―８受容体拮抗薬 |
| US5935945A (en) * | 1996-10-31 | 1999-08-10 | Merck & Co., Inc. | Methods of treating or preventing cardiac arrhythmia |
| US6180632B1 (en) * | 1997-05-28 | 2001-01-30 | Aventis Pharmaceuticals Products Inc. | Quinoline and quinoxaline compounds which inhibit platelet-derived growth factor and/or p56lck tyrosine kinases |
| US6399618B1 (en) | 1997-07-09 | 2002-06-04 | Cardiome Pharma Corp | Compositions and methods for modulating sexual activity |
| TW536401B (en) | 1997-09-03 | 2003-06-11 | Cardiome Pharma Corp | A pharmaceutical composition of N,N-bis(phenylcarbamoylmethyl)dimethylammomum chloride and derivatives for the treatment of pain |
| CN1278166A (zh) | 1997-09-26 | 2000-12-27 | 诺特兰药品公司 | 局部麻醉或抗心律不齐同时产生止痛的氨基环己酰胺的对映体混合物 |
| JP3773644B2 (ja) * | 1998-01-06 | 2006-05-10 | 芝府エンジニアリング株式会社 | 接点材料 |
| US6013830A (en) | 1998-03-30 | 2000-01-11 | Sepracor Inc. | Asymmetric grignard synthesis with cyclic 1,2 aminoalcohols |
| CA2326777C (en) * | 1998-04-01 | 2011-12-20 | Nortran Pharmaceuticals Inc. | Aminocyclohexyl ether compounds and uses thereof |
| US6624761B2 (en) * | 1998-12-11 | 2003-09-23 | Realtime Data, Llc | Content independent data compression method and system |
| US6979685B1 (en) * | 1999-02-12 | 2005-12-27 | Cardiome Pharma Corp. | Cycloalkyl amine compounds and uses thereof |
| WO2000047547A2 (en) | 1999-02-12 | 2000-08-17 | Nortran Pharmaceuticals Inc. | Cycloalkyl amine compounds and uses thereof |
| AU2899400A (en) | 1999-03-04 | 2000-09-21 | Nortran Pharmaceuticals Inc. | Aminocycloalkyl cinnamide compounds for arrhythmia and as analgesics and anesthetics |
| US7507545B2 (en) * | 1999-03-31 | 2009-03-24 | Cardiome Pharma Corp. | Ion channel modulating activity method |
| CA2268590A1 (en) * | 1999-04-12 | 2000-10-12 | Nortran Pharmaceuticals Inc. | Ion channel modulating compounds and uses thereof |
| US6150357A (en) | 1999-05-10 | 2000-11-21 | Merck & Co., Inc. | Potassium channel agonists |
| ES2225553T3 (es) * | 2000-04-20 | 2005-03-16 | F. Hoffmann-La Roche Ag | Derivados de pirrolidina y piperidina y su empleo para el tratamiento de trastornos neurodegenerativos. |
| CA2311483A1 (en) | 2000-06-12 | 2001-12-12 | Gregory N Beatch | IMIDAZO [1,2-A] PYRIDINIC ETHERS AND USES THEREOF |
| US6521619B2 (en) * | 2000-06-29 | 2003-02-18 | Icos Corporation | Aryl phenylcyclopropyl sulfide derivatives and their use as cell adhesion inhibiting anti-inflammatory and immune suppressive agents |
| US6498170B2 (en) * | 2000-07-17 | 2002-12-24 | Wyeth | Cyclamine sulfonamides as β-3 adrenergic receptor agonists |
| US7057053B2 (en) | 2000-10-06 | 2006-06-06 | Cardiome Pharma Corp. | Ion channel modulating compounds and uses thereof |
| US20040049049A1 (en) * | 2002-06-14 | 2004-03-11 | Johnson Matthey Pharmaceutical Materials, Inc. | Stereoselective synthesis of 1,2-disubstituted cycloalkyls |
| GB2407093A (en) | 2002-07-12 | 2005-04-20 | Cardiome Inc | Mutations of voltage-gated potassium channels |
| CA2524323C (en) * | 2003-05-02 | 2012-05-15 | Cardiome Pharma Corp. | Aminocyclohexyl ether compounds and uses thereof |
| WO2004098525A2 (en) | 2003-05-02 | 2004-11-18 | Cardiome Pharma Corp. | Uses of ion channel modulating compounds |
| US7345086B2 (en) * | 2003-05-02 | 2008-03-18 | Cardiome Pharma Corp. | Uses of ion channel modulating compounds |
| WO2005016242A2 (en) * | 2003-06-04 | 2005-02-24 | Cardiome Pharma Corp. | Synthetic process for trans-aminocyclohexyl ether compounds |
| WO2005018635A2 (en) * | 2003-08-07 | 2005-03-03 | Cardiome Pharma Corp. | Ion channel modulating activity i |
| US7345087B2 (en) * | 2003-10-31 | 2008-03-18 | Cardiome Pharma Corp. | Aminocyclohexyl ether compounds and uses thereof |
| US20070197632A1 (en) | 2003-10-31 | 2007-08-23 | Cardiome Pharma Corp | Aminocyclohexyl ether compounds and uses thereof |
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2003
- 2003-10-31 CA CA2524323A patent/CA2524323C/en not_active Expired - Lifetime
- 2003-10-31 JP JP2005510835A patent/JP4919661B2/ja not_active Expired - Lifetime
- 2003-10-31 SI SI200330358T patent/SI1560812T1/sl unknown
- 2003-10-31 ES ES03781611T patent/ES2264776T3/es not_active Expired - Lifetime
- 2003-10-31 AU AU2003287378A patent/AU2003287378B2/en not_active Expired
- 2003-10-31 AT AT03781611T patent/ATE325789T1/de active
- 2003-10-31 SG SG200716599-6A patent/SG167670A1/en unknown
- 2003-10-31 NZ NZ543921A patent/NZ543921A/en not_active IP Right Cessation
- 2003-10-31 EP EP10014986A patent/EP2298735A1/en not_active Withdrawn
- 2003-10-31 PT PT03781611T patent/PT1560812E/pt unknown
- 2003-10-31 AT AT06000750T patent/ATE529401T1/de not_active IP Right Cessation
- 2003-10-31 ES ES06000750T patent/ES2375820T3/es not_active Expired - Lifetime
- 2003-10-31 EP EP03781611A patent/EP1560812B1/en not_active Expired - Lifetime
- 2003-10-31 PL PL378918A patent/PL227937B1/pl unknown
- 2003-10-31 DK DK03781611T patent/DK1560812T3/da active
- 2003-10-31 SG SG2010079697A patent/SG2010079697A/en unknown
- 2003-10-31 WO PCT/US2003/034655 patent/WO2004099137A1/en not_active Ceased
- 2003-10-31 EP EP06000750A patent/EP1666459B1/en not_active Expired - Lifetime
- 2003-10-31 US US10/555,364 patent/US20070099983A1/en not_active Abandoned
- 2003-10-31 BR BRPI0318278A patent/BRPI0318278B8/pt not_active IP Right Cessation
- 2003-10-31 DE DE60305200T patent/DE60305200T2/de not_active Expired - Lifetime
- 2003-10-31 KR KR1020057020862A patent/KR101059379B1/ko not_active Expired - Lifetime
- 2003-10-31 BR BR122018009866A patent/BR122018009866B8/pt active IP Right Grant
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2005
- 2005-10-30 IL IL171653A patent/IL171653A/en active IP Right Grant
- 2005-11-02 NO NO20055130A patent/NO334094B1/no not_active IP Right Cessation
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2006
- 2006-08-09 CY CY20061101114T patent/CY1105137T1/el unknown
- 2006-10-30 JP JP2006294918A patent/JP2007077162A/ja not_active Withdrawn
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2007
- 2007-03-23 US US11/690,361 patent/US7767830B2/en not_active Expired - Lifetime
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2008
- 2008-02-04 RU RU2008104198/04A patent/RU2478617C2/ru active
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2010
- 2010-07-09 US US12/833,423 patent/US8163938B2/en not_active Expired - Lifetime
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2011
- 2011-03-08 AU AU2011201015A patent/AU2011201015B2/en not_active Expired
- 2011-11-24 IL IL216579A patent/IL216579A/en active IP Right Grant
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