BR112015004523B1 - Compostos de tetraciclina, composições farmacêuticas e seus usos - Google Patents
Compostos de tetraciclina, composições farmacêuticas e seus usos Download PDFInfo
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- BR112015004523B1 BR112015004523B1 BR112015004523-5A BR112015004523A BR112015004523B1 BR 112015004523 B1 BR112015004523 B1 BR 112015004523B1 BR 112015004523 A BR112015004523 A BR 112015004523A BR 112015004523 B1 BR112015004523 B1 BR 112015004523B1
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Classifications
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- 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
- C07D207/08—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 hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
- C07D207/09—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/24—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring of the carbon skeleton
- C07C237/26—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring of the carbon skeleton of a ring being part of a condensed ring system formed by at least four rings, e.g. tetracycline
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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
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- 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
- C07D207/08—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 hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
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- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D295/155—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
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- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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Applications Claiming Priority (3)
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| US201261695947P | 2012-08-31 | 2012-08-31 | |
| US61/695,947 | 2012-08-31 | ||
| PCT/US2013/057690 WO2014036502A2 (en) | 2012-08-31 | 2013-08-30 | Tetracycline compounds |
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| BR112015004523A2 BR112015004523A2 (pt) | 2017-07-04 |
| BR112015004523B1 true BR112015004523B1 (pt) | 2020-08-04 |
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Families Citing this family (9)
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| PT2323972E (pt) | 2008-08-08 | 2013-10-09 | Tetraphase Pharmaceuticals Inc | Compostos de tetraciclina substituídos com c7-flúor |
| EP2427425B1 (en) | 2009-05-08 | 2017-03-08 | Tetraphase Pharmaceuticals, Inc. | Tetracycline compounds |
| IN2012DN02502A (https=) | 2009-08-28 | 2015-08-28 | Tetraphase Pharmaceuticals Inc | |
| BR112015004523B1 (pt) | 2012-08-31 | 2020-08-04 | Tetraphase Pharmaceuticals, Inc | Compostos de tetraciclina, composições farmacêuticas e seus usos |
| CA3034891A1 (en) * | 2016-08-30 | 2018-03-08 | Tetraphase Pharmaceuticals, Inc. | Tetracycline compounds and methods of treatment |
| CN110582486B (zh) | 2016-10-19 | 2024-01-12 | 四相制药公司 | 艾若威四环素的结晶形式 |
| WO2020020999A1 (en) | 2018-07-27 | 2020-01-30 | Sandoz Ag | Process for preparing rapidly or very rapidly dissolving tablets comprising freely soluble api |
| CN113444070A (zh) * | 2021-07-28 | 2021-09-28 | 深圳市真味生物科技有限公司 | 一种由手性叔丁基亚磺酰胺合成手性尼古丁的制备方法 |
| CN115448849B (zh) * | 2022-11-10 | 2023-02-03 | 苏州富士莱医药股份有限公司 | 一种2-苄氧基-3-二苄基氨基-5-氟-6-甲基苯甲酸苯酯的制备方法 |
Family Cites Families (112)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE639292A (https=) | ||||
| GB935384A (en) * | 1959-03-30 | 1963-08-28 | Pfizer & Co C | Tetracycline derivatives and preparation thereof |
| US3338963A (en) | 1960-10-28 | 1967-08-29 | American Cyanamid Co | Tetracycline compounds |
| GB1034933A (en) * | 1962-10-29 | 1966-07-06 | American Cyanamid Co | 4-demethylamino-4-substituted amino 6-demethyl tetracyclines |
| US3364123A (en) * | 1963-05-06 | 1968-01-16 | Squibb & Sons Inc | Production of 4n-demethyl-4n-ethyl tetracyclines |
| USRE26253E (en) | 1963-05-17 | 1967-08-15 | And z-alkylamino-g-deoxytetracycline | |
| GB1065715A (en) * | 1964-04-16 | 1967-04-19 | Pfizer & Co C | Tetracycline derivatives |
| US3247226A (en) * | 1964-07-06 | 1966-04-19 | American Cyanamid Co | 4-dimethylamino and 4-hydroxytetracycloxides |
| US3394178A (en) * | 1965-01-26 | 1968-07-23 | Merck & Co Inc | Nu-ethyloxytetracycline |
| GB1077598A (en) | 1965-05-12 | 1967-08-02 | Pfizer & Co C | Preparation of n-demethyl tetracyclines |
| US3304227A (en) | 1965-07-15 | 1967-02-14 | Loyal E Loveless | Antibiotic-containing animal feed |
| US3433709A (en) | 1965-12-07 | 1969-03-18 | American Cyanamid Co | Biological transformation of alpha-6-deoxytetracyclines to tetracyclines |
| US3849493A (en) * | 1966-08-01 | 1974-11-19 | Pfizer | D-ring substituted 6-deoxytetracyclines |
| US3824285A (en) * | 1967-09-13 | 1974-07-16 | Pfizer | 4-oxo-4-dedimethylaminotetracycline-4,6-hemiketals |
| US3947517A (en) | 1969-06-12 | 1976-03-30 | Research Corporation | Stereoselective introduction of tetracyclines hydroxyl group at 12(a) position in synthesis of tetracyclines |
| DE2437487A1 (de) | 1974-08-03 | 1976-02-19 | Merck Patent Gmbh | 7-methoxy-6-thia-tetracycline und verfahren zu ihrer herstellung |
| DE2442829A1 (de) * | 1974-09-06 | 1976-03-18 | Merck Patent Gmbh | Tetracyclische verbindungen und verfahren zu ihrer herstellung |
| YU290176A (en) * | 1976-11-26 | 1982-05-31 | Pliva Zagreb | Process for preparing 4-dedimethylamino-4-arylsulfonamido-5a,6-anhydrotetracycline |
| US4925833A (en) | 1983-12-29 | 1990-05-15 | The Research Foundation Of State University Of New York | Use of tetracycline to enhance bone protein synthesis and/or treatment of osteoporosis |
| US4935412A (en) | 1983-12-29 | 1990-06-19 | The Research Foundation Of State University Of New York | Non-antibacterial tetracycline compositions possessing anti-collagenolytic properties and methods of preparing and using same |
| US4704383A (en) | 1983-12-29 | 1987-11-03 | The Research Foundation Of State University Of New York | Non-antibacterial tetracycline compositions possessing anti-collagenolytic properties and methods of preparing and using same |
| USRE34656E (en) | 1983-12-29 | 1994-07-05 | The Research Foundation Of State University Of New York | Use of tetracycline to enhance bone protein synthesis and/or treatment of bone deficiency |
| US4666897A (en) | 1983-12-29 | 1987-05-19 | Research Foundation Of State University | Inhibition of mammalian collagenolytic enzymes by tetracyclines |
| US5308839A (en) | 1989-12-04 | 1994-05-03 | The Research Foundation Of State University Of New York | Composition comprising non-steroidal anti-inflammatory agent tenidap and effectively non-antibacterial tetracycline |
| JP3016587B2 (ja) | 1989-12-04 | 2000-03-06 | ザ・リサーチ・ファンデーション・オブ・ステート・ユニバーシティ・オブ・ニューヨーク | 非ステロイド抗炎症剤及びテトラサイクリンの配合 |
| US5770588A (en) | 1991-02-11 | 1998-06-23 | The Research Foundation Of State University Of New York | Non-antibacterial tetracycline compositions of the prevention and treatment of root caries |
| US5231017A (en) | 1991-05-17 | 1993-07-27 | Solvay Enzymes, Inc. | Process for producing ethanol |
| DE122006000058I1 (de) | 1991-10-04 | 2007-01-18 | Wyeth Corp | 7-Substituierte-9-substituierte Amino-6-Demethyl-6-Deoxy-Tetracycline |
| USRE40183E1 (en) | 1991-10-04 | 2008-03-25 | Wyeth Holdings Corporation | 7-Substituted-9-substituted amino-6-demethyl-6-deoxytetracyclines |
| US5494903A (en) | 1991-10-04 | 1996-02-27 | American Cyanamid Company | 7-substituted-9-substituted amino-6-demethyl-6-deoxytetracyclines |
| US5258371A (en) | 1992-05-29 | 1993-11-02 | Kuraray Co., Ltd. | Method to reduce connective tissue destruction |
| US6043225A (en) | 1992-06-12 | 2000-03-28 | Board Of Regents Of The University Of Washington | Diagnosis and treatment of arterial chlamydial granuloma |
| US5442059A (en) | 1992-08-13 | 1995-08-15 | American Cyanamid Company | 9-[(substituted glycyl)amido)]-6-demethyl-6-deoxytetracyclines |
| US5284963A (en) | 1992-08-13 | 1994-02-08 | American Cyanamid Company | Method of producing 7-(substituted)-9-[(substituted glycyl)-amidol]-6-demethyl-6-deoxytetra-cyclines |
| US5420272A (en) | 1992-08-13 | 1995-05-30 | American Cyanamid Company | 7-(substituted)-8-(substituted)-9-](substituted glycyl)amido]-6-demethyl-6-deoxytetracyclines |
| US5328902A (en) | 1992-08-13 | 1994-07-12 | American Cyanamid Co. | 7-(substituted)-9-[(substituted glycyl)amido]-6-demethyl-6-deoxytetracyclines |
| SG47520A1 (en) | 1992-08-13 | 1998-04-17 | American Cyanamid Co | New method for the production of 9-amino-6-demethyl-6-deoxytetracycline |
| EP0599397B1 (en) | 1992-11-17 | 1996-08-28 | The Research Foundation Of State University Of New York | Tetracyclines including non-antimicrobial chemically-modified tetracyclines inhibit excessive collagen crosslinking during diabetes |
| US5523297A (en) | 1993-03-02 | 1996-06-04 | The Research Foundation Of State University Of New York | Inhibition of excessive phospholipase A2 activity and/or production by non-antimicrobial tetracyclines |
| US6043231A (en) | 1993-03-02 | 2000-03-28 | The Research Foundation Of State Univ. Of New York | Inhibition of excessive phospholipase A2 activity and/or production by non-antimicrobial tetracyclines |
| US5371076A (en) | 1993-04-02 | 1994-12-06 | American Cyanamid Company | 9-[(substituted glycyl)amido]-6-(substituted)-5-hydroxy-6-deoxytetracyclines |
| US5668122A (en) | 1993-07-28 | 1997-09-16 | Fife; Rose S. | Method to treat cancer with tetracyclines |
| AU1279095A (en) | 1994-02-17 | 1995-09-04 | Pfizer Inc. | 9-(substituted amino)-alpha-6-deoxy-5-oxy tetracycline derivatives, their preparation and their use as antibiotics |
| US5574026A (en) | 1994-12-13 | 1996-11-12 | American Cyanamid Company | Methods for inhibiting angiogenesis proliferation of endothelial or tumor cells and tumor growth |
| US5843925A (en) | 1994-12-13 | 1998-12-01 | American Cyanamid Company | Methods for inhibiting angiogenesis, proliferation of endothelial or tumor cells and tumor growth |
| US5834449A (en) | 1996-06-13 | 1998-11-10 | The Research Foundation Of State University Of New York | Treatment of aortic and vascular aneurysms with tetracycline compounds |
| US5827840A (en) | 1996-08-01 | 1998-10-27 | The Research Foundation Of State University Of New York | Promotion of wound healing by chemically-modified tetracyclines |
| US5789395A (en) | 1996-08-30 | 1998-08-04 | The Research Foundation Of State University Of New York | Method of using tetracycline compounds for inhibition of endogenous nitric oxide production |
| US5919774A (en) | 1996-12-10 | 1999-07-06 | Eli Lilly And Company | Pyrroles as sPLA2 inhibitors |
| US5837696A (en) | 1997-01-15 | 1998-11-17 | The Research Foundation Of State University Of New York | Method of inhibiting cancer growth |
| US5773430A (en) | 1997-03-13 | 1998-06-30 | Research Foundation Of State University Of New York | Serine proteinase inhibitory activity by hydrophobic tetracycline |
| US5929055A (en) | 1997-06-23 | 1999-07-27 | The Research Foundation Of State University Of New York | Therapeutic method for management of diabetes mellitus |
| CA2318580A1 (en) | 1998-01-23 | 1999-07-29 | Mark L. Nelson | Pharmaceutically active compounds and methods of use thereof |
| US6277061B1 (en) | 1998-03-31 | 2001-08-21 | The Research Foundation Of State University Of New York | Method of inhibiting membrane-type matrix metalloproteinase |
| US6015804A (en) | 1998-09-11 | 2000-01-18 | The Research Foundation Of State University Of New York | Method of using tetracycline compounds to enhance interleukin-10 production |
| US5977091A (en) | 1998-09-21 | 1999-11-02 | The Research Foundation Of State University Of New York | Method of preventing acute lung injury |
| US6914057B1 (en) | 1998-09-28 | 2005-07-05 | The Research Foundation Of State University Of New York | Inhibitor of cataract formation |
| US5998390A (en) | 1998-09-28 | 1999-12-07 | The Research Foundation Of State University Of New York | Combination of bisphosphonate and tetracycline |
| KR20010073190A (ko) | 1998-09-28 | 2001-07-31 | 제임스 알. 데니히 | 백내장 형성 억제제 |
| US6231894B1 (en) | 1999-10-21 | 2001-05-15 | Duke University | Treatments based on discovery that nitric oxide synthase is a paraquat diaphorase |
| AU2000257445A1 (en) | 2000-06-16 | 2002-01-02 | Trustees Of Tufts College | 7-n-substituted phenyl tetracycline compounds |
| CN1450989A (zh) | 2000-07-07 | 2003-10-22 | 塔夫茨大学信托人 | 7－取代的四环素化合物 |
| EA013908B1 (ru) | 2000-07-07 | 2010-08-30 | Трастис Оф Тафтс Коллидж | Замещенные соединения миноциклина (варианты), фармацевтическая композиция и способ лечения чувствительного к тетрациклину состояния млекопитающего |
| JP4963771B2 (ja) | 2000-07-07 | 2012-06-27 | トラスティーズ・オブ・タフツ・カレッジ | ７、８および９−置換テトラサイクリン化合物 |
| WO2002072532A1 (en) | 2001-03-13 | 2002-09-19 | Paratek Pharmaceuticals, Inc. | 7, 9-substituted tetracycline compounds |
| WO2002072031A2 (en) | 2001-03-14 | 2002-09-19 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds as synergistic antifungal agents |
| JP2004530661A (ja) | 2001-03-14 | 2004-10-07 | パラテック ファーマシューティカルズ インコーポレイテッド | 抗真菌剤としての置換テトラサイクリン化合物 |
| EP1399414B1 (en) | 2001-04-24 | 2010-01-13 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds for the treatment of malaria |
| US8088820B2 (en) | 2001-04-24 | 2012-01-03 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds for the treatment of malaria |
| EP2329826A1 (en) | 2001-07-13 | 2011-06-08 | Paratek Pharmaceuticals, Inc. | Tetracyclines for the treatment of multiple sclerosis |
| US20060194773A1 (en) | 2001-07-13 | 2006-08-31 | Paratek Pharmaceuticals, Inc. | Tetracyline compounds having target therapeutic activities |
| EP2311799A1 (en) | 2002-01-08 | 2011-04-20 | Paratek Pharmaceuticals, Inc. | 4-dedimethylamino tetracycline compounds |
| JP2005526754A (ja) | 2002-03-08 | 2005-09-08 | パラテック ファーマシューティカルズ インコーポレイテッド | アミノメチル置換されたテトラサイクリン化合物 |
| KR101083498B1 (ko) * | 2002-03-21 | 2011-11-16 | 파라테크 파마슈티컬스, 인크. | 치환된 테트라시클린 화합물 |
| CA2492273C (en) | 2002-07-12 | 2013-02-05 | Paratek Pharmaceuticals, Inc. | 3, 10, and 12a substituted tetracycline compounds |
| WO2004038001A2 (en) | 2002-10-24 | 2004-05-06 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds for the treatment of malaria |
| CA2503446C (en) | 2002-10-24 | 2012-12-18 | Paratek Pharmaceuticals, Inc. | Methods of using substituted tetracycline compounds to modulate rna |
| CA2531728A1 (en) | 2003-07-09 | 2005-02-03 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds |
| WO2005082860A1 (en) | 2004-02-27 | 2005-09-09 | National Research Council Of Canada | Tetracyclines and their use as calpain inhibitors |
| CA2892332C (en) * | 2004-05-21 | 2017-03-21 | President And Fellows Of Harvard College | Synthesis of tetracyclines and analogues thereof |
| AU2005299294B2 (en) | 2004-10-25 | 2012-06-07 | Paratek Pharmaceuticals, Inc. | 4-aminotetracyclines and methods of use thereof |
| EP2269985A3 (en) | 2004-10-25 | 2011-09-21 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds |
| WO2006084265A1 (en) | 2005-02-04 | 2006-08-10 | Paratek Pharmaceuticals, Inc. | 11a, 12-DERIVATIVES OF TETRACYCLINE COMPOUNDS |
| BRPI0607353A2 (pt) | 2005-02-15 | 2009-09-01 | Wyeth Corp | composto de fórmula (i); composição farmacêutica; uso do composto para o tratamento ou controle de infecções bacterianas em animais de sangue quente; processo para a preparação de tetraciclinas 9-(n-substituìdas-n-substituìdas-glicil) de fórmulas 5; 7; 10; e tetraciclina 9-(n-substituìda-n-substituìda glicil) de fómulas 5; 7; 10 |
| JP2009502809A (ja) * | 2005-07-21 | 2009-01-29 | パラテック ファーマシューティカルズ インコーポレイテッド | １０−置換テトラサイクリンおよびその使用方法 |
| EP2298324A1 (en) | 2006-01-24 | 2011-03-23 | Paratek Pharmaceuticals, Inc. | Methods of increasing oral bioavailability of tetracyclines |
| JP5335664B2 (ja) * | 2006-04-07 | 2013-11-06 | プレジデント アンド フェロウズ オブ ハーバード カレッジ | テトラサイクリンおよびその類似体の合成 |
| AU2007249695A1 (en) | 2006-05-15 | 2007-11-22 | Paratek Pharmaceuticals, Inc. | Methods of regulating expression of genes or of gene products using substituted tetracycline compounds |
| WO2008127361A2 (en) | 2006-10-11 | 2008-10-23 | President And Fellows Of Harvard College | Synthesis of enone intermediate |
| WO2008045507A2 (en) | 2006-10-11 | 2008-04-17 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds for treatment of bacillus anthracis infections |
| PL2109602T3 (pl) | 2006-12-21 | 2014-09-30 | Paratek Pharm Innc | Pochodne tetracyliny do leczenia zakażeń bakteryjnych, wirusowych i pasożytniczych |
| TWI334106B (en) | 2006-12-27 | 2010-12-01 | Icp Electronics Inc | Apparatus for converting gray scale and method for the same |
| JP2010523684A (ja) | 2007-04-12 | 2010-07-15 | パラテック ファーマシューティカルズ インコーポレイテッド | テトラサイクリン化合物を用いる、脊髄筋委縮症を治療するための方法 |
| BRPI0823405A2 (pt) | 2007-07-06 | 2012-12-25 | Paratek Pharmaceuticals, Inc. | mÉtodos para sintetizar compostos de tetraciclina substituÍda |
| WO2009073056A1 (en) | 2007-09-07 | 2009-06-11 | Dr. Reddy's Laboratories Ltd. | Novel tetracycline derivatives as antibacterial agents |
| JP2011517697A (ja) | 2008-04-14 | 2011-06-16 | パラテック ファーマシューティカルズ インコーポレイテッド | 置換テトラサイクリン化合物 |
| CA2730377C (en) * | 2008-07-11 | 2017-09-19 | Neumedics | Tetracycline derivatives with reduced antibiotic activity and neuroprotective benefits |
| PT2323972E (pt) | 2008-08-08 | 2013-10-09 | Tetraphase Pharmaceuticals Inc | Compostos de tetraciclina substituídos com c7-flúor |
| WO2010126607A2 (en) | 2009-04-30 | 2010-11-04 | President And Fellows Of Harvard College | Synthesis of tetracyclines and intermediates thereto |
| EP2427425B1 (en) | 2009-05-08 | 2017-03-08 | Tetraphase Pharmaceuticals, Inc. | Tetracycline compounds |
| ES2440000T3 (es) | 2009-05-08 | 2014-01-27 | Tetraphase Pharmaceuticals, Inc. | Compuestos de 8-aza-tetraciclina |
| WO2010132670A2 (en) | 2009-05-13 | 2010-11-18 | Tetraphase Pharmaceuticals, Inc. | Pentacycline compounds |
| IN2012DN02502A (https=) | 2009-08-28 | 2015-08-28 | Tetraphase Pharmaceuticals Inc | |
| EP2544692A4 (en) | 2010-03-10 | 2013-08-07 | Univ Health Network | USE OF TIGECYCLIN FOR THE TREATMENT OF CANCER |
| TWI592390B (zh) | 2010-03-31 | 2017-07-21 | 四相製藥公司 | 聚環狀四環素化合物 |
| TW201245116A (en) * | 2010-08-12 | 2012-11-16 | Tetraphase Pharmaceuticals Inc | Tetracycline analogs |
| WO2012047907A1 (en) | 2010-10-04 | 2012-04-12 | President And Fellows Of Harvard College | Synthesis of c5-substituted tetracyclines, uses thereof, and intermediates thereto |
| BR112015004523B1 (pt) | 2012-08-31 | 2020-08-04 | Tetraphase Pharmaceuticals, Inc | Compostos de tetraciclina, composições farmacêuticas e seus usos |
| MA40836A (fr) | 2014-10-23 | 2017-08-29 | Tetraphase Pharmaceuticals Inc | Procédures de semi-synthèse |
| EP3778567A1 (en) | 2016-01-22 | 2021-02-17 | Sandoz Ag | Crystalline eravacycline bis-hydrochloride |
| CA3034891A1 (en) | 2016-08-30 | 2018-03-08 | Tetraphase Pharmaceuticals, Inc. | Tetracycline compounds and methods of treatment |
| CN110582486B (zh) | 2016-10-19 | 2024-01-12 | 四相制药公司 | 艾若威四环素的结晶形式 |
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