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1. 发明申请

WO2013173326A1 METHODS OF USING (4S,4AS,5AR,12AS)-4- DIMETHYLAMINO-3,10,12,12A-TETRAHYDROXY-7-[(METHOXY(METHYL)AMINO)-METHYL]-1,11-DIOXO-1,4,4A,5,5A,6,11,12A-OCTAHYDRO-NAPHTHACENE-2-CARBOXYLIC ACID AMIDE 审中-公开
标题翻译：使用（4S，4AS，5AR，12AS）-4-二甲基氨基-3,10,12,12a-四氢甲基-7 - [（甲基（甲基）氨基） - 甲基] -1,11-二氧代-1,4- ，4A，5,5A，6,11,12A-OCTAHYDRO-NAPHTHACENE-2-CARBOXYLIC ACID AMATE
公开(公告)号：WO2013173326A1
公开(公告)日：2013-11-21
申请号：PCT/US2013/040933
申请日：2013-05-14
申请人： PARATEK PHARMACEUTICALS, INC. , WARNER CHILCOTT COMPANY, LLC , COULTER, Catherine , JOHNSTON, Sean, M. , SEYEDI, Farzaneh , DEVRIES, Tina, M.
发明人： COULTER, Catherine , JOHNSTON, Sean, M. , SEYEDI, Farzaneh , DEVRIES, Tina, M.
IPC分类号： A61K31/65
CPC分类号： A61K31/65 , A61K33/24 , A61K45/06 , A61K2300/00
摘要： A method of treating a bacterial infection, e.g., a bacterial infection with methicillin resistant Staphylococcus aureus, Helicobacter pylori, Chlamydia trachomatis , or Chlamydia pneumonia , comprising administering to a subject (4S,4aS,5aR,12aS)-4-dimethylamino-3,10,12,12a-tetrahydroxy-7- [(methoxy(methyl)amino)-methyl] -1,11-dioxo-1,4,4a,5,5a,6, 11, 12a-octahydronaphthacene-2-carboxylic acid amide or a pharmaceutically acceptable salt thereof is disclosed. More specifically, a method of treating a bacterial infection comprising administering to a subject crystalline mono hydrochloride salt, crystalline mono mesylate salt or crystalline mono sulfate salt of (4S,4aS,5aR,12aS)-4-dimethylamino-3,10,12,12a-tetrahydroxy-7- [(methoxy(methyl)amino)-methyl]-l,l l-dioxo-l,4,4a,5,5a,6,l l,12a-octahydro- naphthacene-2-carboxylic acid amide is disclosed.
摘要翻译：治疗细菌感染的方法，例如，耐甲氧西林金黄色葡萄球菌，幽门螺杆菌，沙眼衣原体或肺炎衣原体的细菌感染的方法，包括向受试者（4S，4aS，5aR，12aS）-4-二甲基氨基-3， 10,12,12a-四羟基-7 - [（甲氧基（甲基）氨基） - 甲基] -1,11-二氧代-1,4,4a，5,5a，6,11,11a-八氢萘并-2-甲酸酰胺或其药学上可接受的盐。更具体地，涉及治疗细菌感染的方法，其包括给予受试者结晶单盐酸盐，（4S，4aS，5aR，12aS）-4-二甲基氨基-3,10,12， 12a-四羟基-7 - [（甲氧基（甲基）氨基） - 甲基] -1,11-二氧代-1,4,4a，5,5a，6,11a-八氢 - 并四苯-2-羧酸酰胺被披露。

2. 发明申请

WO2012155146A1 CRYSTALLINE SALTS OF (4S,4AS,5AR,12AS)-4-DIMETHYLAMINO-3,10,12,12A-TETRAHYDROXY-7-[(METHOXY(METHYL)AMINO)-METHYL]-1,11-DIOXO-1,4,4A,5,5A,6,11,12A-OCTAHYDRO-NAPHTHACENE-2-CARBOXYLIC ACID AMIDE AND METHODS OF USING THE SAME 审中-公开
标题翻译：（4S，4AS，5AR，12AS）-4-二甲基氨基-3,10,12,12-四氢萘-7-基[（甲基（甲基）氨基） - 甲基] -1,11-二氧代-1,4- ，4A，5,5A，6,11,12A-OCTAHYDRO-NAPHTHACENE-2-羧酸酰胺及其使用方法
公开(公告)号：WO2012155146A1
公开(公告)日：2012-11-15
申请号：PCT/US2012/037838
申请日：2012-05-14
申请人： PARATEK PHARMACEUTICALS, INC. , WARNER CHILCOTT COMPANY, LLC , COULTER, Catherine , JOHNSTON, Sean, M. , SEYEDI, Farzaneh
发明人： COULTER, Catherine , JOHNSTON, Sean, M. , SEYEDI, Farzaneh
IPC分类号： A61K31/65 , C07C237/26
CPC分类号： C07C237/26 , C07B2200/07 , C07B2200/13 , C07C239/20 , C07C309/04 , C07C2103/46 , C07C2603/46
摘要： A crystalline mono hydrochloride salt of (4S,4aS,5aR,12aS)-4-dimethylamino- 3,10, 12, 12a-tetrahydroxy-7-[(methoxy(methyl)amino)-methyl]- 1, 11-dioxo-1,4,4a,5,5a,6,11,12a-octahydro-naphthacene-2-carboxylic acid amide is disclosed having improved stability. In addition, a crystalline mono mesylate salt and crystalline mono sulfate salt of (4S,4aS,5aR,12aS)-4-dimethylamino-3,10,12,12a-tetrahydroxy-7- [(methoxy(methyl)amino)-methyl]-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydro-naphthacene- 2-carboxylic acid amide are also disclosed having improved stability. A pharmaceutical composition containing the crystalline salts and methods of treating inflammatory skin disorders and bacterial infections comprising administering the crystalline salts are also disclosed.
摘要翻译：（4S，4aS，5aR，12aS）-4-二甲基氨基-3,10,12-二羟基-7 - [（甲氧基（甲基）氨基） - 甲基] -1,11-二氧代 - 公开了具有改进的稳定性的1,4,4a，5,5a，6,11,12a-八氢 - 并四烯-2-羧酸酰胺。此外，（4S，4aS，5aR，12aS）-4-二甲基氨基-3,10,12,12a-四羟基-7 - [（甲氧基（甲基）氨基） - 甲基的结晶单甲磺酸盐和结晶一硫酸盐 ] -1,11-二氧代-1,4,4a，5,5a，6,11,12a-八氢 - 并四苯-2-羧酸酰胺也具有改进的稳定性。还公开了含有结晶盐的药物组合物和治疗炎性皮肤病症和细菌感染的方法，包括给予结晶盐。

3. 发明申请

WO2009009042A1 METHODS FOR SYNTHESIZING SUBSTITUTED TETRACYCLINE COMPOUNDS 审中-公开
标题翻译：用于合成取代的四氢化合物化合物的方法
公开(公告)号：WO2009009042A1
公开(公告)日：2009-01-15
申请号：PCT/US2008/008355
申请日：2008-07-07
申请人： PARATEK PHARMACEUTICALS, INC. , SEYEDI, Farzaneh , WARCHOL, Tadeusz , GRIER, Mark
发明人： SEYEDI, Farzaneh , WARCHOL, Tadeusz , GRIER, Mark
IPC分类号： C07C237/26
CPC分类号： C07C231/12 , C07C2603/44 , C07C237/26
摘要： Methods for synthesizing a carboxaldehyde substituted tetracycline compound comprising reacting a tetracycline reactive intermediate under appropriate conditions with carbon monoxide, a palladium catalyst, a phosphine ligand, a silane and a base, such that said carboxaldehyde substituted tetracycline compound is synthesized. The palladium catalyst is chosen from PdCl2 (tBu2PhP)2 dichlorobis (di-tert-butylphenylphosphine palladium (II)] or PdCl2 (DPEPhos) [bis (diphenylphosphinophenyl) ether palladium (II) chloride]. The tetracycline reactive intermediate contains moieties selected from halogens and triflates. Methods of synthesizing a substituted tetracycline compound comprising reacting the carboxaldehyde substituted tetracycline compound under palladium catalyzed coupling conditions, hydrogenolysis conditions or reductive amination conditions.
摘要翻译：合成羧甲醛取代的四环素化合物的方法，包括在合适的条件下使四环素反应性中间体与一氧化碳，钯催化剂，膦配体，硅烷和碱反应，使得所述甲醛取代的四环素化合物合成。钯催化剂选自PdCl2（tBu2PhP）2二氯双（二叔丁基苯基膦钯（II）]或PdCl 2（DPEPhos）[双（二苯基膦基苯基）醚氯化钯（II）]，四环素反应性中间体包含选自卤素合成取代的四环素化合物的方法，包括在钯催化的偶联条件下，氢解条件或还原胺化条件下使羧醛取代的四环素化合物反应。

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