AU2002242203B2 - (2-hydroxy)ethyl-thioureas useful as modulators of alpha2B adrenergic receptors - Google Patents
(2-hydroxy)ethyl-thioureas useful as modulators of alpha2B adrenergic receptors Download PDFInfo
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- AU2002242203B2 AU2002242203B2 AU2002242203A AU2002242203A AU2002242203B2 AU 2002242203 B2 AU2002242203 B2 AU 2002242203B2 AU 2002242203 A AU2002242203 A AU 2002242203A AU 2002242203 A AU2002242203 A AU 2002242203A AU 2002242203 B2 AU2002242203 B2 AU 2002242203B2
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Classifications
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- C07C335/00—Thioureas, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C335/04—Derivatives of thiourea
- C07C335/06—Derivatives of thiourea having nitrogen atoms of thiourea groups bound to acyclic carbon atoms
- C07C335/10—Derivatives of thiourea having nitrogen atoms of thiourea groups bound to acyclic carbon atoms of an unsaturated carbon skeleton
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- 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]
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C335/00—Thioureas, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C335/04—Derivatives of thiourea
- C07C335/06—Derivatives of thiourea having nitrogen atoms of thiourea groups bound to acyclic carbon atoms
- C07C335/08—Derivatives of thiourea having nitrogen atoms of thiourea groups bound to acyclic carbon atoms of a saturated carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C335/00—Thioureas, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C335/04—Derivatives of thiourea
- C07C335/14—Derivatives of thiourea having nitrogen atoms of thiourea groups bound to carbon atoms of rings other than six-membered aromatic rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/10—Systems containing only non-condensed rings with a five-membered ring the ring being unsaturated
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/18—Systems containing only non-condensed rings with a ring being at least seven-membered
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pain & Pain Management (AREA)
- Pharmacology & Pharmacy (AREA)
- Rheumatology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (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)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US09/794,874 | 2001-02-27 | ||
| US09/794,874 US6534542B2 (en) | 2001-02-27 | 2001-02-27 | (2-hydroxy)ethyl-thioureas useful as modulators of α2B adrenergic receptors |
| PCT/US2002/005021 WO2002068384A2 (en) | 2001-02-27 | 2002-02-19 | (2-hydroxy)ethyl-thioureas useful as modulators of alpha2b adrenergic receptors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2002242203A1 AU2002242203A1 (en) | 2003-03-06 |
| AU2002242203B2 true AU2002242203B2 (en) | 2007-01-18 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2002242203A Ceased AU2002242203B2 (en) | 2001-02-27 | 2002-02-19 | (2-hydroxy)ethyl-thioureas useful as modulators of alpha2B adrenergic receptors |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US6534542B2 (enExample) |
| EP (1) | EP1381593A2 (enExample) |
| JP (1) | JP4159363B2 (enExample) |
| AU (1) | AU2002242203B2 (enExample) |
| CA (1) | CA2439838C (enExample) |
| WO (1) | WO2002068384A2 (enExample) |
Families Citing this family (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060280774A1 (en) * | 1995-06-02 | 2006-12-14 | Allergan, Inc. | Compositions and methods for treating glaucoma |
| US5869079A (en) * | 1995-06-02 | 1999-02-09 | Oculex Pharmaceuticals, Inc. | Formulation for controlled release of drugs by combining hydrophilic and hydrophobic agents |
| US6329369B1 (en) * | 1997-12-04 | 2001-12-11 | Allergan Sales, Inc. | Methods of treating pain and other conditions |
| US6726918B1 (en) | 2000-07-05 | 2004-04-27 | Oculex Pharmaceuticals, Inc. | Methods for treating inflammation-mediated conditions of the eye |
| ATE306951T1 (de) | 2000-11-29 | 2005-11-15 | Allergan Inc | Verhinderung von transplantatabstossung im auge |
| US7276522B2 (en) * | 2002-05-21 | 2007-10-02 | Allergan, Inc. | 4-(substituted cycloalkylmethyl) imidazole-2-thiones, 4-(substituted cycloalkenylmethyl) imidazole-2-thiones, 4-(substituted cycloalkylmethyl) imidazol-2-ones, 4-(substituted cycloalkenylmethyl) imidazol-2-ones and related compounds |
| US7358269B2 (en) | 2002-05-21 | 2008-04-15 | Allergan, Inc. | 2-((2-Thioxo-2,3-dihydro-1H-imidazol-4-yl)methyl)-3,4-dihydronapthalen-1(2H)-one |
| US7323485B2 (en) | 2002-05-21 | 2008-01-29 | Allergan, Inc. | 4-(substituted cycloalkylmethyl) imidazole-2-thiones, 4-(substituted cycloalkenylmethyl) imidazole-2-thiones, 4-(substituted cycloalkylmethyl) imidazol-2-ones and 4-(substituted cycloalkenylmethyl) imidazol-2-ones and related compounds |
| US7091232B2 (en) * | 2002-05-21 | 2006-08-15 | Allergan, Inc. | 4-(substituted cycloalkylmethyl) imidazole-2-thiones, 4-(substituted cycloalkenylmethyl) imidazole-2-thiones, 4-(substituted cycloalkylmethyl) imidazol-2-ones and 4-(substituted cycloalkenylmethyl) imidazol-2-ones and related compounds |
| US20050048099A1 (en) | 2003-01-09 | 2005-03-03 | Allergan, Inc. | Ocular implant made by a double extrusion process |
| US20050244469A1 (en) | 2004-04-30 | 2005-11-03 | Allergan, Inc. | Extended therapeutic effect ocular implant treatments |
| KR20070063016A (ko) * | 2004-09-24 | 2007-06-18 | 알러간, 인코포레이티드 | 알파2 아드레날린성 아고니스트로서 작용하는 4-(축합시클릭메틸)-이미다졸-2-티온 |
| JP2008514603A (ja) | 2004-09-24 | 2008-05-08 | アラーガン、インコーポレイテッド | α2アドレナリン作動剤としての4−(ヘテロアリール−メチルおよび置換ヘテロアリール−メチル)−イミダゾール−2−チオン |
| US20070178138A1 (en) * | 2006-02-01 | 2007-08-02 | Allergan, Inc. | Biodegradable non-opthalmic implants and related methods |
| US20070298073A1 (en) * | 2006-06-23 | 2007-12-27 | Allergan, Inc. | Steroid-containing sustained release intraocular implants and related methods |
| US8802128B2 (en) | 2006-06-23 | 2014-08-12 | Allergan, Inc. | Steroid-containing sustained release intraocular implants and related methods |
| WO2008014299A2 (en) * | 2006-07-27 | 2008-01-31 | Allergan, Inc. | Use of an alpha2-agonist composition for the treatment of hyperlipidemia |
| US20080153825A1 (en) * | 2006-12-22 | 2008-06-26 | Allergan Inc. | Alpha-2b receptor agonist and 5ht4 serotonin receptor compositions for treating gastrointestinal motility disorders |
| US20080153881A1 (en) * | 2006-12-22 | 2008-06-26 | Allergan, Inc. | Alpha-2b receptor agonist and acid reducer compositions for treating gastrointestinal motility disorders |
| US20080153927A1 (en) * | 2006-12-22 | 2008-06-26 | Allergan, Inc. | Alpha-2b receptor agonist and relaxant compositions for treating gastrointestinal motility disorders |
| US20100016355A1 (en) | 2006-12-22 | 2010-01-21 | Gil Daniel W | Alpha-2b adrenergic receptor agonist and serotonin-norepinephrine reuptake inhibitor compositions for treating chronic pain |
| US20120083508A1 (en) | 2006-12-22 | 2012-04-05 | Allergan, Inc. | Alpha-2b receptor agonist and anticonvulsant compositions for treating chronic pain |
| US20080153874A1 (en) * | 2006-12-22 | 2008-06-26 | Allergan Inc. | Alpha-2b receptor agonist and anticonvulsant compositions for treating chronic pain |
| WO2009052073A2 (en) * | 2007-10-18 | 2009-04-23 | Allergan, Inc. | Method of treating sensorimotor disorders with alpha-2 adrenergic receptor agonists |
| WO2009052075A2 (en) * | 2007-10-18 | 2009-04-23 | Allergan, Inc. | Method of treating motor disorders with alpha-2b adrenergic receptor agonists |
| WO2009052072A1 (en) * | 2007-10-18 | 2009-04-23 | Allergan, Inc. | Treating motor disorders with 4-(1-(2,3-dimethylphenyl)ethyl)-1h-imidazole-2(3h)-thione |
| WO2011028621A1 (en) | 2009-08-26 | 2011-03-10 | Allergan, Inc. | Method of treating compulsive disorders with alpha-2b adrenergic receptor agonists |
| DK2605771T3 (en) | 2010-08-16 | 2018-07-16 | Allergan Inc | PROCEDURE FOR ACTIVATING REGULATORY T CELLS WITH ALPHA-2B-ADDRENGE RECEPTOR AGONISTS |
| CN109336917A (zh) * | 2013-06-04 | 2019-02-15 | 塞勒创尼克斯公司 | 腈-取代的硅烷和电解质组合物和包含它们的电化学装置 |
| CN105531252B (zh) | 2013-09-12 | 2018-01-09 | 信越化学工业株式会社 | 用于制备β‑环薰衣草醛及其衍生物的方法 |
| WO2015037664A1 (ja) * | 2013-09-12 | 2015-03-19 | 信越化学工業株式会社 | シクロラバンジュロール及びその誘導体の製造方法 |
| RU2552529C1 (ru) * | 2013-11-29 | 2015-06-10 | Федеральное государственное бюджетное учреждение "Медицинский радиологический научный центр" Министерства здравоохранения Российской Федерации (ФГБУ МРНЦ Минздрава России) | Вазопрессорное средство |
| US12440821B2 (en) | 2021-12-13 | 2025-10-14 | Saudi Arabian Oil Company | Method for tracing subterranean formations with oil-soluble organic molecular tracers and extracting them of from oil phases |
| US11725139B2 (en) | 2021-12-13 | 2023-08-15 | Saudi Arabian Oil Company | Manipulating hydrophilicity of conventional dye molecules for water tracer applications |
| US12188350B2 (en) * | 2022-06-08 | 2025-01-07 | Saudi Arabian Oil Company | Fluorescent dye oil tracer compositions |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2161772A (en) * | 1936-04-17 | 1939-06-06 | Monsanto Chemicals | Phenol stabilization |
| US3686303A (en) * | 1967-04-20 | 1972-08-22 | Du Pont | Certain substituted cyclohexyl ureas and thioureas |
| SU795462A3 (ru) | 1975-03-14 | 1981-01-07 | Эдьт Дьедьесерведьесети Дьяр (Фирма) | Способ получени тиокарбамидныхпРОизВОдНыХ |
| US5212176A (en) | 1990-06-29 | 1993-05-18 | Abbott Laboratories | R(+)-terazosin |
| US5580892A (en) * | 1993-10-22 | 1996-12-03 | Allergan | Method for using 2-(2-alkylphenylamino)-oxazolines as adrenergic agents |
| TWI283669B (en) | 1999-06-10 | 2007-07-11 | Allergan Inc | Compounds and method of treatment having agonist-like activity selective at alpha 2B or 2B/2C adrenergic receptors |
| US6313172B1 (en) * | 2000-04-13 | 2001-11-06 | Allergan Sales, Inc. | Methods and compositions for modulating alpha adrenergic receptor activity |
-
2001
- 2001-02-27 US US09/794,874 patent/US6534542B2/en not_active Expired - Fee Related
-
2002
- 2002-02-19 WO PCT/US2002/005021 patent/WO2002068384A2/en not_active Ceased
- 2002-02-19 AU AU2002242203A patent/AU2002242203B2/en not_active Ceased
- 2002-02-19 EP EP02707824A patent/EP1381593A2/en not_active Withdrawn
- 2002-02-19 JP JP2002567898A patent/JP4159363B2/ja not_active Expired - Fee Related
- 2002-02-19 CA CA2439838A patent/CA2439838C/en not_active Expired - Fee Related
Non-Patent Citations (1)
| Title |
|---|
| J Org Chem vol 48(4) 1983, pp 507-512 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2439838C (en) | 2012-01-24 |
| EP1381593A2 (en) | 2004-01-21 |
| JP2004524312A (ja) | 2004-08-12 |
| JP4159363B2 (ja) | 2008-10-01 |
| WO2002068384A3 (en) | 2003-03-06 |
| WO2002068384A2 (en) | 2002-09-06 |
| CA2439838A1 (en) | 2002-09-06 |
| US6534542B2 (en) | 2003-03-18 |
| US20020161051A1 (en) | 2002-10-31 |
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| FGA | Letters patent sealed or granted (standard patent) | ||
| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |