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11. 发明授权

US06750348B1 Chemokine receptor binding heterocyclic compounds 失效
标题翻译：趋化因子受体结合杂环化合物
公开(公告)号：US06750348B1
公开(公告)日：2004-06-15
申请号：US09535314
申请日：2000-03-24
申请人： Gary Bridger , Renato Skerlj , Al Kaller , Curtis Harwig , David Bogucki , Trevor R. Wilson , Jason Crawford , Ernest J. McEachern , Bem Atsma , Siqiao Nan , Yuanxi Zhou , Dominique Schols
发明人： Gary Bridger , Renato Skerlj , Al Kaller , Curtis Harwig , David Bogucki , Trevor R. Wilson , Jason Crawford , Ernest J. McEachern , Bem Atsma , Siqiao Nan , Yuanxi Zhou , Dominique Schols
IPC分类号： C07D21516
CPC分类号： C07D239/42 , A61K45/06 , C07D213/38 , C07D215/40 , C07D401/12 , C07D401/14 , C07D405/14 , C07D409/14 , C07D413/14 , C07D417/14 , C07D451/04 , C07D471/04 , C07D487/04
摘要： This invention relates to a novel class of heterocyclic compounds that bind chemokine receptors, inhibiting the binding of their natural ligands thereby. These compounds result in protective effects against infection by HIV through binding to chemokine receptors, including CXCR4 and CCR5, thus inhibiting the subsequent binding by these chemokines. The present invention provides a compound of Formula I wherein, W is a nitrogen atom and Y is absent or, W is a carbon atom and Y═H; R1 to R7 may be the same or different and are independently selected from hydrogen or straight, branched or cyclic C1-6 alkyl; R8 is a substituted heterocyclic group or a substituted aromatic group Ar is an aromatic or heteroaromatic ring each optionally substituted at single or multiple, non-linking positions with electron-donating or withdrawing groups; n and n′ are independently, 0-2; X is a group of the formula: Wherein, Ring A is an optionally substituted, saturated or unsaturated 5 or 6-membered ring, and P is an optionally substituted carbon atom, an optionally substituted nitrogen atom, sulfur or oxygen atom. Ring B is an optionally substituted 5 to 7-membered ring. Ring A and Ring B in the above formula can be connected to the group W from any position via the group V, wherein V is a chemical bond, a (CH2)n″ group (where n″=0-2) or a C═O group. Z is, (1) a hydrogen atom, (2) an optionally substituted C1-6 alkyl group, (3) a C0-6 alkyl group substituted with an optionally substituted aromatic or heterocyclic group, (4) an optionally substituted C0-6 alkylamino or C3-7 cycloalkylamino group, (5) an optionally substituted carbonyl group or sulfonyl. These compounds further include any pharmaceutically acceptable acid addition salts and metal complexes thereof and any stereoisomeric forms and mixtures of stereoisomeric forms thereof.
摘要翻译：本发明涉及结合趋化因子受体的新一类杂环化合物，从而抑制其天然配体的结合。这些化合物通过结合趋化因子受体（包括CXCR4和CCR5）导致HIV感染的保护作用，从而抑制随后与这些趋化因子的结合。本发明提供式I化合物，其中W是氮原子，Y不存在，或W是碳原子，Y = H; R 1至R 7可以相同或不同并且独立地选自来自氢或直链，支链或环状的C 1-6烷基; R 8是取代的杂环基或取代的芳族基团Ar是芳族或杂芳族环，其各自任选在单个或多个非连接位置被取代，具有给电子或取代基; n和n'独立地是0-2; X是下式的基团：其中环A是任选取代的饱和或不饱和的5或6元环，并且P是任选取代的碳原子，任选取代的氮原子，硫或氧原子。环B是任选取代的5至7元环。上述式中的环A和环B可以通过组V从任何位置连接到基团W，其中V是化学键，（CH2）n“基团（其中n”= 0-2）或一个C = O组。 Z为（1）氢原子，（2）任选取代的C 1-6烷基，（3）被任意取代的芳族或杂环基团取代的C 0-6烷基，（4）任选取代的C 0-6 烷基氨基或C 3-7环烷基氨基，（5）任选取代的羰基或磺酰基。这些化合物还包括其任何药学上可接受的酸加成盐和金属络合物以及其立体异构体形式及其立体异构形式的混合物。

12. 发明申请

US20100105915A1 CHEMOKINE RECEPTOR BINDING HETEROCYCLIC COMPOUNDS 审中-公开
标题翻译：化合物受体结合杂环化合物
公开(公告)号：US20100105915A1
公开(公告)日：2010-04-29
申请号：US12612488
申请日：2009-11-04
申请人： Gary J. BRIDGER , Renato Skerlj , Ai Kaller , Curtis Harwig , David Bogucki , Trevor R. Wilson , Jason Crawford , Ernest J. Mceachern , Bem Atsma , Siqiao Nan , Yuanxi Zhou , Dominique Schols
发明人： Gary J. BRIDGER , Renato Skerlj , Ai Kaller , Curtis Harwig , David Bogucki , Trevor R. Wilson , Jason Crawford , Ernest J. Mceachern , Bem Atsma , Siqiao Nan , Yuanxi Zhou , Dominique Schols
IPC分类号： C07D401/02
CPC分类号： C07D239/42 , A61K45/06 , C07D213/38 , C07D215/40 , C07D401/12 , C07D401/14 , C07D405/14 , C07D409/14 , C07D413/14 , C07D417/14 , C07D451/04 , C07D471/04 , C07D487/04
摘要： Heterocyclic compounds that bind chemokine receptors and inhibit the binding of their natural ligands are disclosed. The invention compounds are protective against infection by HIV and exert effects characteristic of antagonists to the CXCR4 receptor.
摘要翻译：公开了结合趋化因子受体并抑制其天然配体结合的杂环化合物。本发明化合物可防止HIV感染并发挥拮抗剂对CXCR4受体特征的作用。

13. 发明申请

US20070060591A1 Chemokine receptor binding heterocyclic compounds 审中-公开
标题翻译：趋化因子受体结合杂环化合物
公开(公告)号：US20070060591A1
公开(公告)日：2007-03-15
申请号：US11599066
申请日：2006-11-13
申请人： Gary Bridger , Eva Boehringer , Dominique Schols , Renato Skerlj , David Bogucki
发明人： Gary Bridger , Eva Boehringer , Dominique Schols , Renato Skerlj , David Bogucki
IPC分类号： A61K31/52 , A61K31/496 , A61K31/4439
CPC分类号： C07D401/12 , A61K31/33 , A61K31/4439 , A61K31/496 , A61K31/52 , C07D257/02 , C07D403/12 , C07D413/12 , C07D417/12 , Y02A50/411
摘要： The present invention is drawn to novel antiviral compounds, pharmaceutical compositions and their use. More specifically this invention is drawn to derivatives of monocyclic polyamines which have activity in standard tests against HIV- or FIV-infected cells as well as other biological activity related to binding of ligands to chemokine receptors that mediate a number of mammalian embryonic developmental processes.
摘要翻译：本发明涉及新的抗病毒化合物，药物组合物及其应用。更具体地，本发明涉及在针对HIV或FIV感染的细胞的标准测试中具有活性的单环多胺的衍生物以及与介导多种哺乳动物胚胎发育过程的配体与趋化因子受体的结合相关的其它生物活性。

14. 发明申请

US20060264434A1 Chemokine receptor binding heterocyclic compounds 失效
公开(公告)号：US20060264434A1
公开(公告)日：2006-11-23
申请号：US11494943
申请日：2006-07-27
申请人： Gary Bridger , Renato Skerlj , Al Kaller , Curtis Harwig , David Bogucki , Trevor Wilson , Jason Crawford , Ernest McEachern , Bem Atsma , Siqiao Nan , Yuanxi Zhou , Dominique Schols
发明人： Gary Bridger , Renato Skerlj , Al Kaller , Curtis Harwig , David Bogucki , Trevor Wilson , Jason Crawford , Ernest McEachern , Bem Atsma , Siqiao Nan , Yuanxi Zhou , Dominique Schols
IPC分类号： A61K31/5377 , A61K31/4545 , A61K31/4439 , C07D401/02 , C07D413/02
CPC分类号： C07D239/42 , A61K45/06 , C07D213/38 , C07D215/40 , C07D401/12 , C07D401/14 , C07D405/14 , C07D409/14 , C07D413/14 , C07D417/14 , C07D451/04 , C07D471/04 , C07D487/04
摘要： This invention relates to a novel class of heterocyclic compounds that bind chemokine receptors, inhibiting the binding of their natural ligands thereby. These compounds result in protective effects against infection by HIV through binding to chemokine receptors, including CXCR4 and CCR5, thus inhibiting the subsequent binding by these chemokines. The present invention provides a compound of Formula I wherein, W is a nitrogen atom and Y is absent or, W is a carbon atom and Y=H; R1 to R7 may be the same or different and are independently selected from hydrogen or straight, branched or cyclic C1-6 alkyl; R8 is a substituted heterocyclic group or a substituted aromatic group Ar is an aromatic or heteroaromatic ring each optionally substituted at single or multiple, non-linking positions with electron-donating or withdrawing groups; n and n′ are independently, 0-2; X is a group of the formula: Wherein, Ring A is an optionally substituted, saturated or unsaturated 5 or 6-membered ring, and P is an optionally substituted carbon atom, an optionally substituted nitrogen atom, sulfur or oxygen atom. Ring B is an optionally substituted 5 to 7-membered ring. Ring A and Ring B in the above formula can be connected to the group W from any position via the group V, wherein V is a chemical bond, a (CH2)n″ group (where n″=0-2) or a C═O group. Z is, (1) a hydrogen atom, (2) an optionally substituted C1-6 alkyl group, (3) a C0-6 alkyl group substituted with an optionally substituted aromatic or heterocyclic group, (4) an optionally substituted C0-6 alkylamino or C3-7 cycloalkylamino group, (5) an optionally substituted carbonyl group or sulfonyl. These compounds further include any pharmaceutically acceptable acid addition salts and metal complexes thereof and any stereoisomeric forms and mixtures of stereoisomeric forms thereof.

15. 发明授权

US07091217B2 Chemokine receptor binding heterocyclic compounds 失效
公开(公告)号：US07091217B2
公开(公告)日：2006-08-15
申请号：US10799386
申请日：2004-03-11
申请人： Gary Bridger , Renato Skerlj , Al Kaller , Curtis Harwig , David Bogucki , Trevor R. Wilson , Jason Crawford , Ernest J. McEachern , Bem Atsma , Siqiao Nan , Yuanxi Zhou , Dominique Schols , Christopher Dennis Smith , Maria Rosaria Di Fluri
发明人： Gary Bridger , Renato Skerlj , Al Kaller , Curtis Harwig , David Bogucki , Trevor R. Wilson , Jason Crawford , Ernest J. McEachern , Bem Atsma , Siqiao Nan , Yuanxi Zhou , Dominique Schols , Christopher Dennis Smith , Maria Rosaria Di Fluri
IPC分类号： A61K31/47 , C07D221/02
CPC分类号： C07D213/81 , A61K31/4709 , C07D213/38 , C07D213/65 , C07D215/40 , C07D231/12 , C07D233/56 , C07D249/08 , C07D401/12 , C07D401/14 , C07D405/14 , C07D409/14 , C07D413/14 , C07D417/14 , C07D471/04 , C07D491/04 , C07D493/04 , Y02A50/411
摘要： Compounds which modulate chemokine receptor activities are disclosed. These compounds are preferably tertiary amines comprising tetrahydroquinoline and benzimidazole.

16. 发明申请

US20050277670A1 Chemokine receptor binding compounds 失效
公开(公告)号：US20050277670A1
公开(公告)日：2005-12-15
申请号：US11012002
申请日：2004-12-13
申请人： Yuanxi Zhou , Gary Bridger , Renato Skerlj , David Bogucki , Wen Yang , Elyse Bourque , Jonathan Langille , Tong-Shuang Li , Markus Metz , Maria Di Fluri , Siqiao Nan
发明人： Yuanxi Zhou , Gary Bridger , Renato Skerlj , David Bogucki , Wen Yang , Elyse Bourque , Jonathan Langille , Tong-Shuang Li , Markus Metz , Maria Di Fluri , Siqiao Nan
IPC分类号： A61K31/4545 , C07D401/12 , C07D401/14 , C07D413/14 , C07D417/14 , C12N20060101 , C07D43/02
CPC分类号： C07D401/14 , C07D401/12 , C07D413/14 , C07D417/14
摘要： The present invention relates to chemokine receptor binding compounds, pharmaceutical compositions and their use. More specifically, the present invention relates to modulators of chemokine receptor activity, preferably modulators of CCR5. These compounds demonstrate protective effects against infection of target cells by a human immunodeficiency virus (HIV).

17. 发明申请

US20050154005A1 Methods to modulate conditions mediated by the CXCR4 receptor 有权
标题翻译：调节由CXCR4受体介导的病症的方法
公开(公告)号：US20050154005A1
公开(公告)日：2005-07-14
申请号：US10991944
申请日：2004-11-17
申请人： Gary Bridger , Eva Boehringer , Zhongren Wang , Dominique Schols , Renato Skerlj , David Bogucki
发明人： Gary Bridger , Eva Boehringer , Zhongren Wang , Dominique Schols , Renato Skerlj , David Bogucki
IPC分类号： A61K31/381 , A61K31/395 , A61K31/4178 , A61K31/4353 , A61K31/44 , A61K31/4427 , A61K31/4433 , A61K31/444 , A61K31/496 , A61K31/497 , A61K31/52 , A61K31/675 , A61P1/00 , A61P19/02 , A61P21/02 , A61P25/00 , A61P31/12 , A61P31/18 , A61P35/00 , C07D257/02 , C07D401/06 , C07D401/12 , C07D403/12 , C07D409/12 , C07D471/06 , C07D471/08 , C07D473/00 , C07D487/08 , A61K31/4745 , C07D487/14
CPC分类号： C07D473/00 , C04B35/632 , C07D257/02 , C07D401/06 , C07D401/12 , C07D403/12 , C07D409/12 , C07D471/06
摘要： The present invention is drawn to novel antiviral compounds, pharaceutical compositions and their use. More specifically this invention is drawn to derivatives of monocyclic polyamines wihich have activity in standard tests against HIV- or FIV-infected cells as well as other biological activity related to binding of ligands to chemokine receptors that mediate a number of mammalian embryonic developmental processes.
摘要翻译：本发明涉及新型抗病毒化合物，药物组合物及其用途。更具体地，本发明涉及在具有针对HIV或FIV感染细胞的标准测试中具有活性的单环多胺衍生物以及与介导多种哺乳动物胚胎发育过程的配体与趋化因子受体的结合相关的其它生物活性。

18. 发明授权

US07354934B2 Chemokine receptor binding heterocyclic compounds with enhanced efficacy 有权
公开(公告)号：US07354934B2
公开(公告)日：2008-04-08
申请号：US11301725
申请日：2005-12-13
申请人： Gary J. Bridger , Al Kaller , Curtis Harwig , Renato T. Skerlj , David Bogucki , Trevor R. Wilson , Jason B. Crawford , Ernest J. McEachern , Bem Atsma , Siqiao Nan , Yuanxi Zhou , Dominique Schols , Christopher Dennis Smith , Maria R. Di Fluri
发明人： Gary J. Bridger , Al Kaller , Curtis Harwig , Renato T. Skerlj , David Bogucki , Trevor R. Wilson , Jason B. Crawford , Ernest J. McEachern , Bem Atsma , Siqiao Nan , Yuanxi Zhou , Dominique Schols , Christopher Dennis Smith , Maria R. Di Fluri
IPC分类号： A61K31/4709 , C07D403/12
CPC分类号： C07D401/14 , C07D235/14 , C07D401/12 , C07D403/12 , C07D471/04 , C07D471/06 , C07D491/04
摘要： The invention relates to heterocyclic compounds consisting of a core nitrogen atom surrounded by three pendant groups, wherein two of the three pendant groups are preferably benzimidazolyl methyl and tetrahydroquinolyl, and the third pendant group contains N and optionally contains additional rings. The compounds bind to chemokine receptors, including CXCR4 and CCR5, and demonstrate protective effects against infection of target cells by a human immunodeficiency virus (HIV).

19. 发明申请

US20060252795A1 Chemokine receptor binding heterocyclic compounds 失效
公开(公告)号：US20060252795A1
公开(公告)日：2006-11-09
申请号：US11487038
申请日：2006-07-14
申请人： Gary Bridger , Renato Skerlj , Al Kaller , Curtis Harwig , David Bogucki , Trevor Wilson , Jason Crawford , Ernest McEachern , Bem Atsma , Siqiao Nan , Yuanxi Zhou , Dominique Schols , Christopher Smith , Maria Di Fluri
发明人： Gary Bridger , Renato Skerlj , Al Kaller , Curtis Harwig , David Bogucki , Trevor Wilson , Jason Crawford , Ernest McEachern , Bem Atsma , Siqiao Nan , Yuanxi Zhou , Dominique Schols , Christopher Smith , Maria Di Fluri
IPC分类号： A61K31/4709
CPC分类号： C07D213/81 , A61K31/4709 , C07D213/38 , C07D213/65 , C07D215/40 , C07D231/12 , C07D233/56 , C07D249/08 , C07D401/12 , C07D401/14 , C07D405/14 , C07D409/14 , C07D413/14 , C07D417/14 , C07D471/04 , C07D491/04 , C07D493/04 , Y02A50/411
摘要： Compounds which modulate chemokine receptor activities are disclosed. These compounds are preferably tertiary amines comprising tetrahydroquinoline and benzimidazole.

20. 发明申请

US20060100240A1 Chemokine receptor binding heterocyclic compounds with enhanced efficacy 有权
公开(公告)号：US20060100240A1
公开(公告)日：2006-05-11
申请号：US11301725
申请日：2005-12-13
申请人： Gary Bridger , Ai Kaller , Curtis Harwig , Renato Skerlj , David Bogucki , Trevor Wilson , Jason Crawford , Ernest McEachern , Bem Atsma , Siqiao Nan , Yuanxi Zhou , Dominique Schols , Christopher Smith , Maria Di Fluri
发明人： Gary Bridger , Ai Kaller , Curtis Harwig , Renato Skerlj , David Bogucki , Trevor Wilson , Jason Crawford , Ernest McEachern , Bem Atsma , Siqiao Nan , Yuanxi Zhou , Dominique Schols , Christopher Smith , Maria Di Fluri
IPC分类号： A61K31/4709 , C07D403/02 , C07D403/14
CPC分类号： C07D401/14 , C07D235/14 , C07D401/12 , C07D403/12 , C07D471/04 , C07D471/06 , C07D491/04
摘要： The invention relates to heterocyclic compounds consisting of a core nitrogen atom surrounded by three pendant groups, wherein two of the three pendant groups are preferably benzimidazolyl methyl and tetrahydroquinolyl, and the third pendant group contains N and optionally contains additional rings. The compounds bind to chemokine receptors, including CXCR4 and CCR5, and demonstrate protective effects against infection of target cells by a human immunodeficiency virus (HIV).

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