公开(公告)号：US07250413B2

公开(公告)日：2007-07-31

申请号：US11114384

申请日：2005-04-26

申请人： Keith Combrink ,  Susan Harran ,  Daniel Denton ,  Zhenkun Ma

发明人： Keith Combrink ,  Susan Harran ,  Daniel Denton ,  Zhenkun Ma

IPC分类号： C07D498/08 ,  C07D519/00 ,  A61K31/4709 ,  A61K31/496 ,  A61P31/04

CPC分类号： C07D498/08 ,  C07D498/18 ,  C07D519/00

摘要： Compounds of the current invention relate to rifamycin derivatives having antimicrobial activities, including activities against drug-resistant microorganisms. More specifically, compounds of the current invention relate to C-25 carbamate derivatives of rifamycin having another functional group or pharmacophore covalently attached to this position through a carbamate linkage. The resulting compounds exert their antimicrobial activity through a dual-function mechanism and therefore exhibit reduced frequency of resistance.

摘要翻译： 本发明的化合物涉及具有抗微生物活性的利福霉素衍生物，包括抗耐药微生物的活性。 更具体地，本发明的化合物涉及具有另一官能团的利福霉素的C-25氨基甲酸酯衍生物或通过氨基甲酸酯键共价连接到该位置的药效团。 所得化合物通过双功能机制发挥其抗微生物活性，因此表现出降低的抗性频率。

公开(公告)号：US20050256096A1

公开(公告)日：2005-11-17

申请号：US11114384

申请日：2005-04-26

申请人： Keith Combrink ,  Susan Harran ,  Daniel Denton ,  Zhenkun Ma

发明人： Keith Combrink ,  Susan Harran ,  Daniel Denton ,  Zhenkun Ma

IPC分类号： C07D491/14 ,  C07D498/08 ,  C07D498/18 ,  C07D519/00

CPC分类号： C07D498/08 ,  C07D498/18 ,  C07D519/00

摘要： Compounds of the current invention relate to rifamycin derivatives having antimicrobial activities, including activities against drug-resistant microorganisms. More specifically, compounds of the current invention relate to C-25 carbamate derivatives of rifamycin having another functional group or pharmacophore covalently attached to this position through a carbamate linkage. The resulting compounds exert their antimicrobial activity through a dual-function mechanism and therefore exhibit reduced frequency of resistance.

摘要翻译： 本发明的化合物涉及具有抗微生物活性的利福霉素衍生物，包括抗耐药微生物的活性。 更具体地，本发明的化合物涉及具有另一官能团的利福霉素的C-25氨基甲酸酯衍生物或通过氨基甲酸酯键共价连接到该位置的药效团。 所得化合物通过双功能机制发挥其抗微生物活性，因此表现出降低的抗性频率。

公开(公告)号：US20050261262A1

公开(公告)日：2005-11-24

申请号：US11034195

申请日：2005-01-12

申请人： Zhenkun Ma ,  Yafei Jin ,  Jing Li ,  Charles Ding ,  Keith Minor ,  Jamie Longgood ,  In Kim ,  Susan Harran ,  Keith Combrink ,  Timothy Morris

发明人： Zhenkun Ma ,  Yafei Jin ,  Jing Li ,  Charles Ding ,  Keith Minor ,  Jamie Longgood ,  In Kim ,  Susan Harran ,  Keith Combrink ,  Timothy Morris

IPC分类号： A61K31/33 ,  A61K31/395 ,  C07D491/14 ,  C07D498/08

CPC分类号： C07D498/00

摘要： Rifamycin derivatives having antimicrobial activities, including activities against drug-resistant microorganisms are claimed in this invention. The inventive rifamycin derivatives are uniquely designed in that they have a rifamycin moiety covalently linked to a linker group through the C-3 carbon of the rifamycin moiety and the linker is, in turn covalently linked to a therapeutic moiety or antibacterial agent/pharmacophore. The therapeutic moiety can be a quinolone, an oxazolidinone, a macrolide, an aminoglycoside, a tetracycline core or a structure/pharmacophore associated with an antibacterial agent.

摘要翻译： 本发明要求具有抗微生物活性的利福霉素衍生物，包括抗药性微生物的活性。 本发明的利福霉素衍生物是唯一设计的，因为它们具有通过利福霉素部分的C-3碳与连接基共价连接的利福霉素部分，接头又与治疗部分或抗菌剂/药效基团共价连接。 治疗部分可以是喹诺酮，恶唑烷酮，大环内酯，氨基糖苷，四环素核心或与抗菌剂相关的结构/药效团。

公开(公告)号：US07247634B2

公开(公告)日：2007-07-24

申请号：US11034195

申请日：2005-01-12

申请人： Zhenkun Ma ,  Yafei Jin ,  Jing Li ,  Charles Z. Ding ,  Keith P. Minor ,  Jamie C. Longgood ,  In Ho Kim ,  Susan Harran ,  Keith Combrink ,  Timothy W. Morris

发明人： Zhenkun Ma ,  Yafei Jin ,  Jing Li ,  Charles Z. Ding ,  Keith P. Minor ,  Jamie C. Longgood ,  In Ho Kim ,  Susan Harran ,  Keith Combrink ,  Timothy W. Morris

IPC分类号： C07D498/08 ,  A61K31/395 ,  A61P31/04

CPC分类号： C07D498/00

摘要： Rifamycin derivatives having antimicrobial activities, including activities against drug-resistant microorganisms are claimed in this invention. The inventive rifamycin derivatives are uniquely designed in that they have a rifamycin moiety covalently linked to a linker group through the C-3 carbon of the rifamycin moiety and the linker is, in turn covalently linked to a therapeutic moiety or antibacterial agent/pharmacophore. The therapeutic moiety can be a quinolone, an oxazolidinone, a macrolide, an aminoglycoside, a tetracycline core or a structure/pharmacophore associated with an antibacterial agent.

摘要翻译： 本发明要求具有抗微生物活性的利福霉素衍生物，包括抗药性微生物的活性。 本发明的利福霉素衍生物是唯一设计的，因为它们具有通过利福霉素部分的C-3碳与连接基共价连接的利福霉素部分，接头又与治疗部分或抗菌剂/药效基团共价连接。 治疗部分可以是喹诺酮，恶唑烷酮，大环内酯，氨基糖苷，四环素核心或与抗菌剂相关的结构/药效团。

公开(公告)号：US20060019986A1

公开(公告)日：2006-01-26

申请号：US11186425

申请日：2005-07-21

申请人： Charles Ding ,  Zhenkun Ma ,  Jing Li ,  Susan Harran ,  Yong He ,  Keith Minor ,  In Kim ,  Jamie Longgood ,  Yafei Jin ,  Keith Combrink

发明人： Charles Ding ,  Zhenkun Ma ,  Jing Li ,  Susan Harran ,  Yong He ,  Keith Minor ,  In Kim ,  Jamie Longgood ,  Yafei Jin ,  Keith Combrink

IPC分类号： A61K31/4745 ,  C07D491/14

CPC分类号： C07D401/12 ,  C07D455/02

摘要： Rifamycin derivatives having the following structure of general formula I (both hydroquinone and corresponding quinone (C1-C4) forms): or its salts, hydrates or prodrugs thereof; wherein a preferred R1 comprises hydrogen or acetyl and a prefered R2 comprises hydrogen, methyl or other lower alkyls; wherein asterik (*) denotes the carbon bearing the chiral center, wherein absolute configuration is assigned as R or S. Methods of preparation of the aforementioned rifamycin derivatives are also described. The compounds exhibit antimicrobial activities, including activities against drug-resistant microorganisms.

摘要翻译： 具有以下通式I结构的利福霉素衍生物（氢醌和对应的醌（C 1 -C 4））形成）：或其盐，水合物或前药; 其中优选的R 1包括氢或乙酰基，优选的R 2 H 2包括氢，甲基或其它低级烷基; 其中asterik（*）表示带有手性中心的碳，其中绝对构型被指定为R或S.还描述了上述利福霉素衍生物的制备方法。 这些化合物表现出抗菌活性，包括抵抗耐药微生物的活性。

公开(公告)号：US20060019985A1

公开(公告)日：2006-01-26

申请号：US11186187

申请日：2005-07-21

申请人： Zhenkun Ma ,  Jing Li ,  Susan Harran ,  Yong He ,  Keith Minor ,  In Kim ,  Charles Ding ,  Jamie Longgood ,  Yafei Jin ,  Keith Combrink

发明人： Zhenkun Ma ,  Jing Li ,  Susan Harran ,  Yong He ,  Keith Minor ,  In Kim ,  Charles Ding ,  Jamie Longgood ,  Yafei Jin ,  Keith Combrink

IPC分类号： A61K31/4745 ,  C07D491/14

CPC分类号： C07D401/12 ,  C07D455/02

摘要： Novel rifamycin derivatives of formula I (both hydroquinone and corresponding quinone (C1-C4) forms): or their salts, hydrates or prodrugs thereof, wherein: a preferred R comprises hydrogen, acetyl; L is a linker, a preferred linker group elements selected from any combination of 1 to 5 groups shown FIG. 1, provided L is not wherein R1 is H, methyl or alkyl. The inventive compounds exhibit valuable antibiotic properties. Formulations having these compounds can be used in the control or prevention of infectious diseases in mammals, both humans and non-humans. In particular, the compounds exhibit a pronounced antibacterial activity, even against multiresistant strains of microbes.

摘要翻译： 式I的新型利福霉素衍生物（氢醌和相应的醌（C 1 -C 4））形成）：或其盐，水合物或前药，其中：优选的R 包括氢，乙酰基; L是接头，优选的连接基团元素选自1至5个组的任何组合，如图1所示。 1，其中L不是其中R 1是H，甲基或烷基。 本发明化合物显示出有价值的抗生素性质。 具有这些化合物的制剂可以用于控制或预防哺乳动物，包括人和非人的感染性疾病。 特别地，这些化合物甚至显示出显着的抗菌活性，即使是针对多抗菌菌株的微生物。

公开(公告)号：US07238694B2

公开(公告)日：2007-07-03

申请号：US11034279

申请日：2005-01-12

申请人： Charles Z. Ding ,  Yafei Jin ,  Jamie C. Longgood ,  Zhenkun Ma ,  Jing Li ,  In Ho Kim ,  Keith P. Minor ,  Susan Harran

发明人： Charles Z. Ding ,  Yafei Jin ,  Jamie C. Longgood ,  Zhenkun Ma ,  Jing Li ,  In Ho Kim ,  Keith P. Minor ,  Susan Harran

IPC分类号： C07D498/08 ,  C07D519/00 ,  A61K31/4709 ,  A61K31/496 ,  A61P31/04

CPC分类号： C07D498/08 ,  C07D519/00

摘要： The present invention relates to rifamycin 3-iminomethylenyl (—CH═N—) derivatives having antimicrobial activities, including activities against drug-resistant microorganisms. The claimed rifamycin derivative has a rifamycin moiety covalently linked to a linker through an iminomethylenyl (—CH═N—) group at the C-3 carbon of the rifamycin moiety and the linker is, in turn, covalently linked to a quinolone structure or its pharmacophore within the DNA gyrase and topoisomerase IV inhibitor family. The inventive rifamycins are novel and exhibit activity against both rifampin and ciprofloxacin-resistant microorganisms.

摘要翻译： 本发明涉及具有抗菌活性的利福霉素3-亚氨基亚甲基（-CH-N-）衍生物，其包括抗药性微生物的活性。 所要求的利福霉素衍生物具有通过利莫霉素部分的C-3碳上的亚氨基亚甲基（-CH-N-）基团与连接体共价连接的利福霉素部分，并且连接体又与喹诺酮结构共价连接或其 DNA促旋酶和拓扑异构酶IV抑制剂家族内的药效团。 本发明的利福霉素是新颖的，并且表现出抵抗利福平和环丙沙星抗性微生物的活性。

公开(公告)号：US07226931B2

公开(公告)日：2007-06-05

申请号：US11186425

申请日：2005-07-21

申请人： Charles Z. Ding ,  Zhenkun Ma ,  Jing Li ,  Susan Harran ,  Yong He ,  Keith P. Minor ,  In Ho Kim ,  Jamie C. Longgood ,  Yafei Jin ,  Keith D. Combrink

发明人： Charles Z. Ding ,  Zhenkun Ma ,  Jing Li ,  Susan Harran ,  Yong He ,  Keith P. Minor ,  In Ho Kim ,  Jamie C. Longgood ,  Yafei Jin ,  Keith D. Combrink

IPC分类号： C07D498/08 ,  A61K31/4709 ,  A61P31/04

CPC分类号： C07D401/12 ,  C07D455/02

摘要： Rifamycin derivatives having the following structure of general formula I (both hydroquinone and corresponding quinone (C1-C4) forms): or its salts, hydrates or prodrugs thereof; wherein a preferred R1 comprises hydrogen or acetyl and a prefered R2 comprises hydrogen, methyl or other lower alkyls; wherein asterik (*) denotes the carbon bearing the chiral center, wherein absolute configuration is assigned as R or S. Methods of preparation of the aforementioned rifamycin derivatives are also described. The compounds exhibit antimicrobial activities, including activities against drug-resistant microorganisms.

摘要翻译： 具有以下通式I结构的利福霉素衍生物（氢醌和对应的醌（C 1 -C 4））形成）：或其盐，水合物或前药; 其中优选的R 1包括氢或乙酰基，优选的R 2 H 2包括氢，甲基或其它低级烷基; 其中asterik（*）表示带有手性中心的碳，其中绝对构型被指定为R或S.还描述了上述利福霉素衍生物的制备方法。 这些化合物表现出抗菌活性，包括抵抗耐药微生物的活性。

公开(公告)号：US07666864B2

公开(公告)日：2010-02-23

申请号：US12411220

申请日：2009-03-25

申请人： Charles Z. Ding ,  Genliang Lu ,  Keith Combrink ,  Dianjun D. Chen ,  Minsoo Song ,  Jiancheng Wang ,  Zhenkun Ma ,  Brian Desmond Palmer ,  Adrian Blaser ,  Andrew M. Thompson ,  Iveta Kmentova ,  Hamish Scott Sutherland ,  William Alexander Denny

发明人： Charles Z. Ding ,  Genliang Lu ,  Keith Combrink ,  Dianjun D. Chen ,  Minsoo Song ,  Jiancheng Wang ,  Zhenkun Ma ,  Brian Desmond Palmer ,  Adrian Blaser ,  Andrew M. Thompson ,  Iveta Kmentova ,  Hamish Scott Sutherland ,  William Alexander Denny

IPC分类号： C07D498/04 ,  A61K31/424 ,  A61K31/5365 ,  A61K31/553

CPC分类号： C07D498/04

摘要： The current invention provides a series of bicyclic nitroimidazole-substituted phenyl oxazolidinones in which a bicyclic nitroimidazole pharmacophore is covalently bonded to a phenyl oxazolidinone, their pharmaceutical compositions, and the method of use of the compositions for prevention and treatment of bacterial infections. The bicyclic nitroimidazole-substituted phenyl oxazolidinones possess surprising antibacterial activity against wild-type and resistant strains of pathogens, and are therefore useful for the prevention, control and treatment of a number of human and veterinary bacterial infections caused by these pathogens, such as Mycobacterium tuberculosis.

摘要翻译： 本发明提供了一系列双环硝基咪唑取代的苯基恶唑烷酮，其中双环硝基咪唑药效团与苯基恶唑烷酮共价键合，其药物组合物，以及组合物用于预防和治疗细菌感染的方法。 双环硝基咪唑取代的苯基恶唑烷酮对于野生型和抗性病原体菌株具有惊人的抗菌活性，因此可用于预防，控制和治疗由这些病原体引起的许多人和兽医细菌感染如结核分枝杆菌 。

公开(公告)号：US20090281088A1

公开(公告)日：2009-11-12

申请号：US12411220

申请日：2009-03-25

申请人： Charles Z. Ding ,  Genliang Lu ,  Keith Combrink ,  Dianjun D. Chen ,  Minsoo Song ,  Jiancheng Wang ,  Zhenkun Ma ,  Brian Desmond Palmer ,  Adrian Blaser ,  Andrew M. Thompson ,  Iveta Kmentova ,  Hamish Scott Sutherland ,  William Alexander Denny

发明人： Charles Z. Ding ,  Genliang Lu ,  Keith Combrink ,  Dianjun D. Chen ,  Minsoo Song ,  Jiancheng Wang ,  Zhenkun Ma ,  Brian Desmond Palmer ,  Adrian Blaser ,  Andrew M. Thompson ,  Iveta Kmentova ,  Hamish Scott Sutherland ,  William Alexander Denny

IPC分类号： A61K31/5365 ,  C07D498/04 ,  A61K31/551 ,  A61K31/496 ,  A61K31/4439 ,  A61K31/506 ,  A61P31/04

CPC分类号： C07D498/04

摘要： The current invention provides a series of bicyclic nitroimidazole-substituted phenyl oxazolidinones in which a bicyclic nitroimidazole pharmacophore is covalently bonded to a phenyl oxazolidinone, their pharmaceutical compositions, and the method of use of the compositions for prevention and treatment of bacterial infections. The bicyclic nitroimidazole-substituted phenyl oxazolidinones possess surprising antibacterial activity against wild-type and resistant strains of pathogens, and are therefore useful for the prevention, control and treatment of a number of human and veterinary bacterial infections caused by these pathogens, such as Mycobacterium tuberculosis.

摘要翻译： 本发明提供了一系列双环硝基咪唑取代的苯基恶唑烷酮，其中双环硝基咪唑药效团与苯基恶唑烷酮共价键合，其药物组合物，以及组合物用于预防和治疗细菌感染的方法。 双环硝基咪唑取代的苯基恶唑烷酮对于野生型和抗性病原体菌株具有惊人的抗菌活性，因此可用于预防，控制和治疗由这些病原体引起的许多人和兽医细菌感染如结核分枝杆菌 。