公开(公告)号：US20090281088A1

公开(公告)日：2009-11-12

申请号：US12411220

申请日：2009-03-25

Applicant: 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

Inventor： 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: A61K31/5365 ,  C07D498/04 ,  A61K31/551 ,  A61K31/496 ,  A61K31/4439 ,  A61K31/506 ,  A61P31/04

CPC classification number: C07D498/04

Abstract: 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.

Abstract translation: 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：US07250413B2

公开(公告)日：2007-07-31

申请号：US11114384

申请日：2005-04-26

Applicant: Keith Combrink ,  Susan Harran ,  Daniel Denton ,  Zhenkun Ma

Inventor： Keith Combrink ,  Susan Harran ,  Daniel Denton ,  Zhenkun Ma

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

CPC classification number: C07D498/08 ,  C07D498/18 ,  C07D519/00

Abstract: 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.

Abstract translation: 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：US07666864B2

公开(公告)日：2010-02-23

申请号：US12411220

申请日：2009-03-25

Applicant: 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

Inventor： 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: C07D498/04 ,  A61K31/424 ,  A61K31/5365 ,  A61K31/553

CPC classification number: C07D498/04

Abstract: 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.

Abstract translation: 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：US20050261262A1

公开(公告)日：2005-11-24

申请号：US11034195

申请日：2005-01-12

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

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

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

CPC classification number: C07D498/00

Abstract: 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.

Abstract translation: 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：US20090143373A1

公开(公告)日：2009-06-04

申请号：US12269652

申请日：2008-11-12

Applicant: Charles Z. Ding ,  Yafei Jin ,  Keith Combrink ,  In Ho Kim

Inventor： Charles Z. Ding ,  Yafei Jin ,  Keith Combrink ,  In Ho Kim

IPC: A61K31/4709 ,  C07D498/04 ,  C07D471/20 ,  A61K31/5383 ,  A61P31/04

CPC classification number: C07D491/20 ,  C07D498/16

Abstract: The compounds include substituted rifamycin derivatives in which a quinolone carboxylic acid pharmacophore is covalently bonded to a benzoxazinorifamycin or a spiropiperidinorifamycin. The rifamycin derivatives are useful as antimicrobial agents and are effective against a number of human and veterinary Gram positive and Gram negative pathogens. The advantage of the inventive compounds is that both the rifamycin and quinolone antibacterial pharmacophores are co-delivered with matched pharmacokinetics to the targeted pathogens of interests. Delivery of multiple antibacterial pharmacophores simultaneously to the targeted pathogens has the maximum chance of achieving synergy and minimizing the development of resistance to the antibiotics given.

Abstract translation: 化合物包括取代的利福霉素衍生物，其中喹诺酮羧酸药效团与苯并恶嗪利福霉素或螺哌啶利多霉素共价键合。 利福霉素衍生物可用作抗微生物剂，并且对许多人和兽医革兰氏阳性和革兰氏阴性病原体有效。 本发明化合物的优点在于利福霉素和喹诺酮类抗菌药代动力剂与匹配的药代动力学共同输送到感兴趣的靶向病原体。 同时向目标病原体递送多个抗菌药代动力，最大限度地实现协同作用，并最大限度地减少给予抗生素的耐药性。

公开(公告)号：US07247634B2

公开(公告)日：2007-07-24

申请号：US11034195

申请日：2005-01-12

Applicant: 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

Inventor： 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: C07D498/08 ,  A61K31/395 ,  A61P31/04

CPC classification number: C07D498/00

Abstract: 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.

Abstract translation: 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：US06919331B2

公开(公告)日：2005-07-19

申请号：US10309505

申请日：2002-12-04

Applicant: Kuo-Long Yu ,  Xiangdong Wang ,  Yaxiong Sun ,  Christopher Cianci ,  Jan Willem Thuring ,  Keith Combrink ,  Nicholas Meanwell ,  Yi Zhang ,  Rita L. Civiello

Inventor： Kuo-Long Yu ,  Xiangdong Wang ,  Yaxiong Sun ,  Christopher Cianci ,  Jan Willem Thuring ,  Keith Combrink ,  Nicholas Meanwell ,  Yi Zhang ,  Rita L. Civiello

IPC: C07D235/26 ,  C07D401/06 ,  C07D403/06 ,  C07D413/14 ,  C07D471/04 ,  C07D513/04

CPC classification number: C07D401/06 ,  C07D235/26 ,  C07D403/06 ,  C07D413/14 ,  C07D471/04 ,  C07D513/04

Abstract: The present invention concerns antiviral compounds, their methods of preparation and their compositions, and use in the treatment of viral infections. More particularly, the invention provides heterocyclic substituted 2-methylbenzimidazole derivatives for the treatment of respiratory syncytial virus infection.

Abstract translation: 本发明涉及抗病毒化合物，其制备方法及其组合物，以及用于治疗病毒感染的用途。 更具体地，本发明提供了用于治疗呼吸道合胞病毒感染的杂环取代的2-甲基苯并咪唑衍生物。

公开(公告)号：US06506738B1

公开(公告)日：2003-01-14

申请号：US09952736

申请日：2001-09-14

Applicant: Kuo-Long Yu ,  Rita Civiello ,  Keith Combrink ,  Hatice Belgin Gulgeze ,  Bradley C. Pearce ,  Xiangdong Wang ,  Nicholas A. Meanwell ,  Yi Zhang

Inventor： Kuo-Long Yu ,  Rita Civiello ,  Keith Combrink ,  Hatice Belgin Gulgeze ,  Bradley C. Pearce ,  Xiangdong Wang ,  Nicholas A. Meanwell ,  Yi Zhang

IPC: C07D40114

CPC classification number: C07D403/14 ,  C07D235/20 ,  C07D405/14 ,  C07D413/14 ,  C07F9/65583

Abstract: The present invention concerns antiviral compounds, their compositions, and use in the treatment of viral infections. More particularly, the invention provides benzimidazolone derivatives for the treatment of respiratory syncytial virus infection.

Abstract translation: 本发明涉及抗病毒化合物，其组合物和用于治疗病毒感染的用途。 更具体地，本发明提供了用于治疗呼吸道合胞病毒感染的苯并咪唑酮衍生物。

公开(公告)号：US07884099B2

公开(公告)日：2011-02-08

申请号：US12269652

申请日：2008-11-12

Applicant: Charles Z. Ding ,  Yafei Jin ,  Keith Combrink ,  In Ho Kim

Inventor： Charles Z. Ding ,  Yafei Jin ,  Keith Combrink ,  In Ho Kim

IPC: C07D491/20 ,  C07D498/16 ,  A61K31/498 ,  A61K31/5383

CPC classification number: C07D491/20 ,  C07D498/16

Abstract: The compounds include substituted rifamycin derivatives in which a quinolone carboxylic acid pharmacophore is covalently bonded to a benzoxazinorifamycin or a spiropiperidinorifamycin. The rifamycin derivatives are useful as antimicrobial agents and are effective against a number of human and veterinary Gram positive and Gram negative pathogens. The advantage of the inventive compounds is that both the rifamycin and quinolone antibacterial pharmacophores are co-delivered with matched pharmacokinetics to the targeted pathogens of interests. Delivery of multiple antibacterial pharmacophores simultaneously to the targeted pathogens has the maximum chance of achieving synergy and minimizing the development of resistance to the antibiotics given.

Abstract translation: 化合物包括取代的利福霉素衍生物，其中喹诺酮羧酸药效团与苯并恶嗪利福霉素或螺哌啶利多霉素共价键合。 利福霉素衍生物可用作抗微生物剂，并且对许多人和兽医革兰氏阳性和革兰氏阴性病原体有效。 本发明化合物的优点在于利福霉素和喹诺酮类抗菌药代动力剂与匹配的药代动力学共同输送到感兴趣的靶向病原体。 同时向目标病原体递送多个抗菌药代动力，最大限度地实现协同作用，并最大限度地减少给予抗生素的耐药性。

公开(公告)号：US20060019986A1

公开(公告)日：2006-01-26

申请号：US11186425

申请日：2005-07-21

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

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

IPC: A61K31/4745 ,  C07D491/14

CPC classification number: C07D401/12 ,  C07D455/02

Abstract: 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.

Abstract translation: 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。