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1. 发明申请

WO2011054947A1 THIADIAZOLIDINEDIOXIDE P2X7 RECEPTOR ANTAGONISTS 审中-公开
标题翻译：噻二唑二酮P2X7受体拮抗剂
公开(公告)号：WO2011054947A1
公开(公告)日：2011-05-12
申请号：PCT/EP2010/066962
申请日：2010-11-08
申请人： GLAXO GROUP LIMITED , DEAN, David, Kenneth , WALTER, Daryl, Simon
发明人： DEAN, David, Kenneth , WALTER, Daryl, Simon
IPC分类号： C07D285/10 , A61K31/33 , A61P25/00
CPC分类号： C07D285/10
摘要： The invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof wherein: R 1 is C 1-3 alkyl or C 1 fluoroalkyl-CH 2 ; R 2 is hydrogen, C 1-4 alkyl, C 1 fluoroalkyl-CH 2 -, C 3-6 cycloalkyl, C 3-6 cycloalkyl-methyl-, optionally substituted benzyl, or optionally substituted heteroaryl-(CH 2 ) n -, wherein n is 0 or 1, wherein in R 2 the benzyl is optionally substituted on the ring with one or two substituents independently being methyl, methoxy, fluorine or chlorine, and wherein in R 2 the heteroaryl-(CH 2 ) n - optionally substituted on the heteroaryl ring with one or two substituents independently being C 1-3 alkyl, CF 3 , methoxy, a halogen atom, or cyano; and wherein: R 3 , R 4 , R 5 , R 6 and R 7 independently are hydrogen, a halogen atom, C 1-4 alkyl, trifluoromethyl, or cyano, such that one or both of R 3 and R 7 is or are a group other than hydrogen.
摘要翻译：本发明提供式（I）化合物或其药学上可接受的盐，其中：R 1为C 1-3烷基或C 1 -C 6烷基-CH 2; R 2是氢，C 1-4烷基，C 1-4烷基-CH 2 - ，C 3-6环烷基，C 3-6环烷基 - 甲基 - ，任选取代的苄基或任选取代的杂芳基 - （CH 2）n - ，其中n是0或1，苄基在环上任选被一个或两个取代基取代，独立地为甲基，甲氧基，氟或氯，并且其中在R 2中，杂芳基环上任选被一个或两个取代基取代的杂芳基 - （CH 2）n - ，CF 3，甲氧基，卤素原子或氰基; 并且其中：R 3，R 4，R 5，R 6和R 7独立地是氢，卤素原子，C 1-4烷基，三氟甲基或氰基，使得R 3和R 7中的一个或两个是氢或不是氢的基团。

2. 发明申请

WO2006040149A9 HETEROCYCLIC KETONE COMPOUNDS FOR TREATING ALZHEIMER'S DISEASE 审中-公开
标题翻译：用于治疗阿尔茨海默病的杂环酮酮化合物
公开(公告)号：WO2006040149A9
公开(公告)日：2006-08-24
申请号：PCT/EP2005011002
申请日：2005-10-11
申请人： GLAXO GROUP LTD , DEMONT EMMANUEL HUBERT , REDSHAW SALLY , WALTER DARYL SIMON
发明人： DEMONT EMMANUEL HUBERT , REDSHAW SALLY , WALTER DARYL SIMON
IPC分类号： C07D513/06 , A61K31/554 , A61P25/28
CPC分类号： C07D513/06
摘要： The present invention relates to novel ketone compounds' of formula (I) wherein, inter alla, A-B represents -NR 5 p ' SO 2 -; -W- represents -CH 2 -, -(CH 2 ) 2 -, -(CH 2 ) 3 - or -C(H)=C(H)-; X-Y-Z represents -C=CR 8 -NR 9 -, having Asp2 (ß-secretase, BACE1 or Memapsin-2) inhibitory activity, processes for their preparation, to -compositions containing them and to their use in the treatment of diseases characterised by elevated ß- amyloid levels or ß-amyloid deposits, particularly Alzheimer's disease.
摘要翻译：本发明涉及式（I）的新型酮化合物，其中，全部是AB表示-NR 5 SO 2 - ; -W-表示-CH 2 - ， - （CH 2）2 - ， - （CH 2）2 - 3或-C（H）= C（H） - ; XYZ表示具有Asp2（ß-分泌酶，BACE1或Memapsin-2）抑制活性的C = CR 8 -NR 9 - 含有它们并用于治疗以β-淀粉样蛋白水平升高或β-淀粉样蛋白沉积物为特征的疾病，特别是阿尔茨海默氏病。

3. 发明申请

WO2005058915A1 TRICYCLIC INDOLE HYDROXYETHYLAMINE DERIVATIVES AND THEIR USE IN THE TREATMENT OF ALZHEIMER'S DISEASE 审中-公开
标题翻译：三羟甲基氨基甲酸衍生物及其在治疗阿尔茨海默病中的应用
公开(公告)号：WO2005058915A1
公开(公告)日：2005-06-30
申请号：PCT/EP2004/014076
申请日：2004-12-09
申请人： GLAXO GROUP LIMITED , REDSHAW, Sally , DEMONT, Emmanuel, Hubert , WALTER, Daryl, Simon
发明人： REDSHAW, Sally , DEMONT, Emmanuel, Hubert , WALTER, Daryl, Simon
IPC分类号： C07D513/06
CPC分类号： C07D513/06
摘要： The present invention relates to novel hydroxyethylamine compounds having Asp2 (β-secretase, BACE1 or Memapsin) inhibitory activity of formula (I), processes for their preparation, to compositions containing them and to their use in the treatment of diseases characterised by elevated β-amyloid levels or β-amyloid deposits, particularly Alzheimer's disease. Formula (I) wherein, inter alia, A-B represents -NR 5 -SO 2 - or -NR 5 -CO-; R 5 represents hydrogen, C 1-6 alkyl, C 3-6 alkenyl, C 3-6 alkynyl, C 3-10 cycloalkyl, -C 0-6 alkylaryl, -C 0-6 alkyl-heteroaryl, -C 0-6 alkyl-heterocyclyl, -C 3-10 cycloalkyl-aryl or -C 3-10 cycloalkyl-heteroaryl; -W- represents -CH 2 -, -(CH 2 ) 2 -, -(CH 2 ) 3 -, -C(H)=C(H)- or -CH 2 -C(H)=C(H)-; X-Y-Z represents -C=CR 8 -NR 9 -;
摘要翻译：本发明涉及具有式（I）的Asp2（β-分泌酶，BACE1或Memapsin）抑制活性，其制备方法，含有它们的组合物及其用于治疗特征为升高的β- 淀粉样蛋白水平或β-淀粉样蛋白沉积物，特别是阿尔茨海默病。式（I）其中特别地，A-B表示-NR 5 -SO 2 - 或-NR 5 -CO-; R 5表示氢，C 1-6烷基，C 3-6烯基，C 3-6炔基，C 3-10环烷基，-C 0-6烷基芳基，-C 0-6烷基 - 杂芳基，-C 0-6烷基 - 杂环基， C3-10环烷基 - 芳基或-C3-10环烷基 - 杂芳基; -W-表示-CH 2 - ， - （CH 2）2 - ， - （CH 2）3 - ， - C（H）= C（H） - 或-CH 2 -C（H）= C（H） - ; X-Y-Z表示-C = CR 8 -NR 9 - ;

4. 发明申请

WO2004111022A1 3-(1,1-DIOXOTETRAHYDRO-1,2-THIAZIN-2-YL) or 3-(1,1-DOXO-ISOTHIAZOLIDIN-2YL) SUBSTITUTED BENZAMIDE COMPOUNDS AS ASP2 INHIBITORS 审中-公开
标题翻译：作为ASP2抑制剂的3-（1,1-二氧杂环戊二烯-1,2-噻嗪-2-基）或3-（1,1-二氧杂 - 异亮氨酸-2YL）取代的苯甲酰化合物
公开(公告)号：WO2004111022A1
公开(公告)日：2004-12-23
申请号：PCT/EP2004/006594
申请日：2004-06-17
申请人： GLAXO GROUP LIMITED , DEMONT, Emmanuel, Hubert , REDSHAW, Sally , WALTER, Daryl, Simon
发明人： DEMONT, Emmanuel, Hubert , REDSHAW, Sally , WALTER, Daryl, Simon
IPC分类号： C07D275/02
CPC分类号： C07D275/02 , C07D279/02 , C07D417/10
摘要： The present invention relates to hydroxyethylene compounds of formula (I); having A sp2 (β-secretase, BACE1 or Memapsin) inhibitory activity, processes for their preparation, to compositions containing them and to their use in the treatment of diseases characterized by elevated β-amyloid levels or β-amyloid deposits, particularly Alzheimer's disease wherein R 1 represents a group of formula Z c .
摘要翻译：本发明涉及式（I）的羟基亚乙基化合物; 具有Sp2（β-分泌酶，BACE1或Memapsin）抑制活性，其制备方法，含有它们的组合物及其用于治疗特征在于升高的β-淀粉样蛋白水平或β-淀粉样蛋白沉积物的疾病，特别是阿尔茨海默氏病，其中 R 1表示式Z c的基团。

5. 发明申请

WO2009077559A3 5-OXO-3-PYRROLIDINECARBOXAMIDE DERIVATIVES AS P2X7 MODULATORS 审中-公开
标题翻译：作为P2X7调节剂的5-OXO-3-吡咯烷酰胺酰胺衍生物
公开(公告)号：WO2009077559A3
公开(公告)日：2009-09-24
申请号：PCT/EP2008067733
申请日：2008-12-17
申请人： GLAXO GROUP LTD , STEADMAN JON GRAHAM ANTHONY , WALTER DARYL SIMON
发明人： STEADMAN JON GRAHAM ANTHONY , WALTER DARYL SIMON
IPC分类号： A61K31/4015 , A61P25/00 , A61P29/00
CPC分类号： A61K31/4015
摘要： The present invention provides a compound of formula (IA) or a pharmaceutically acceptable salt thereof: wherein: R1 represents C1-4 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C3-6 cycloalkylmethyl-, phenyl-X- or heteroaryl, any of which may be optionally substituted; X represents -(CR12R13)n-; n represents 0 to 2; and R7, R8, R9, R10 and R11 independently represent H, halogen, or cyano; or optionally substituted C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl or C3-6 cycloalkyl; such that at least two of R7, R8, R9, R10 and R11 represent a group other than H and at least one of R7 and R11 represents a group other than H; and wherein the compound is other than N-[(2,4-dichlorophenyl)methyl]-5-oxo-1-(phenylmethyl)-3-pyrrolidinecarboxamide. The compounds and salts are thought to modulate P2X7 receptor function and be capable of antagonizing the effects of ATP at the P2X7 receptor.
摘要翻译：本发明提供式（IA）化合物或其药学上可接受的盐：其中：R 1表示C 1-4烷基，C 2-6烯基，C 2-6炔基，C 3-6环烷基，C 3-6环烷基甲基 - ，苯基 - X-或杂芳基，它们中的任何一个可被任选取代; X代表 - （CR 12 R 13）n - n表示0至2; 并且R 7，R 8，R 9，R 10和R 11独立地表示H，卤素或氰基; 或任选取代的C 1-6烷基，C 2-6烯基，C 2-6炔基或C 3-6环烷基; 使得R 7，R 8，R 9，R 10和R 11中的至少两个表示除H以外的基团并且R 7和R 11中的至少一个表示除H以外的基团; 并且其中所述化合物不是N - [（2,4-二氯苯基）甲基] -5-氧代-1-（苯基甲基）-3-吡咯烷甲酰胺。认为化合物和盐调节P2X 7受体功能并能够拮抗ATP在P2X 7受体上的作用。

6. 发明申请

WO2009074518A1 COMBINATIONS OF PROLINAMIDE P2X7 MODULATORS WITH FURTHER THERAPEUTIC AGENTS 审中-公开
标题翻译：丙酰胺P2X7调节剂与进一步治疗剂的组合
公开(公告)号：WO2009074518A1
公开(公告)日：2009-06-18
申请号：PCT/EP2008/066890
申请日：2008-12-05
申请人： GLAXO GROUP LIMITED , MICHEL, Anton Duval , WALTER, Daryl Simon
发明人： MICHEL, Anton Duval , WALTER, Daryl Simon
IPC分类号： A61K31/4015 , A61K31/402 , A61K31/4402 , A61K31/4406 , A61K45/06 , A61P11/00 , A61P19/00 , A61P25/00 , A61P29/00 , A61P43/00
CPC分类号： A61K45/06 , A61K31/4015 , A61K31/402 , A61K31/4402 , A61K31/4406 , A61K31/635 , A61K2300/00
摘要： The invention provides a combination comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof: formula (I), together with a further therapeutic agent or agents; and the use of the combination in the treatment or prevention of pain, inflammation or a neurodegenerative disease. The compounds of formula (I) are thought to be P2X7 receptor antagonists. The compound of formula (I) is preferably N- {[2-chloro-3-(trifluoromethyl)phenyl]methyl}- 1 -methyl-5- oxo-L -prolinamide. The further therapeutic agent can e.g. be methotrexate, an NSAID, a TNFα inhibitor, sulfasalazine, a statin, a glucocorticoid agent, an anti-IL-1 monoclonal antibody, or an anti-CD20 monoclonal antibody; e.g. for the treatment of rheumatoid arthritis. The further therapeutic agent can be capable of treating inflammatory or neuropathic pain, e.g. paracetamol, an opioid (e.g. morphine, fentanyl, oxycodone, or tramadol), pregabalin, gabapentin, gabapentin enacarbil, or carbamazepine.
摘要翻译：本发明提供了包含式（I）化合物或其药学上可接受的盐：式（I）与另外的治疗剂或药剂的组合; 以及该组合在治疗或预防疼痛，炎症或神经变性疾病中的应用。式（I）的化合物被认为是P2X7受体拮抗剂。式（I）化合物优选为N - {[2-氯-3-（三氟甲基）苯基]甲基} -1-甲基-5-氧代-L-脯氨酰胺。另外的治疗剂可以例如甲氨蝶呤，NSAID，TNFa抑制剂，柳氮磺胺吡啶，他汀类，糖皮质激素药，抗IL-1单克隆抗体或抗CD20单克隆抗体; 例如用于治疗类风湿性关节炎。另外的治疗剂可以能够治疗炎性或神经性疼痛，例如，对乙酰氨基酚，阿片样物质（如吗啡，芬太尼，羟考酮或曲马多），普瑞巴林，加巴喷丁，加巴喷丁恩卡巴尔或卡马西平。

7. 发明申请

WO2009053459A1 4-BENZ0YL-1-SUBSTITUTED-PIPERAZIN-2-0NE DERIVATIVES AS P2X7 MODULATORS 审中-公开
标题翻译：作为P2X7调节剂的4-苄氧基-1-取代的哌嗪-2-酮衍生物
公开(公告)号：WO2009053459A1
公开(公告)日：2009-04-30
申请号：PCT/EP2008/064429
申请日：2008-10-24
申请人： GLAXO GROUP LIMITED , CHAMBERS, Laura, Jane , COLLIS, Katharine, Laura , DEAN, David, Kenneth , MUNOZ-MURIEDAS, Jorge , STEADMAN, Jon Graham Anthony , WALTER, Daryl Simon
发明人： CHAMBERS, Laura, Jane , COLLIS, Katharine, Laura , DEAN, David, Kenneth , MUNOZ-MURIEDAS, Jorge , STEADMAN, Jon Graham Anthony , WALTER, Daryl Simon
IPC分类号： C07D241/08 , C07D401/06 , C07D401/10 , C07D403/10 , C07D407/06 , A61K31/496 , A61P29/00 , A61P19/02 , A61P25/28
CPC分类号： C07D241/08 , C07D401/06 , C07D401/10 , C07D403/10 , C07D407/06
摘要： The invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof wherein: A is C 1-6 alkyl, C 3-6 cycloalkyl, -CH 2 -R 6 , -CHMe-R 7 , -CMe 2 -R 7 , or optionally substituted aryl; wherein, when A is optionally substituted aryl, said aryl group is optionally substituted with 1 to 3 substituents, which may be the same or different, selected from the group consisting of halogen, C 1-6 alkyl, -CF 3 , C 1-4 alkoxy, C 1 fluoroalkoxy, cyano, NR 8 R 9 ; and pyridyl wherein the pyridyl is optionally substituted by one methyl; R 1 is chlorine, fluorine, -CF 3 , cyano or C 1-6 alkyl; R 2 , R 3 and R 5 independently are hydrogen, fluorine, chlorine, -CF 3 , cyano or C 1-6 alkyl, such that at least one of R 2 , R 3 and R 5 is other than hydrogen; R 4 is hydrogen. These compounds and salts are thought to be P2X7 receptor antagonists. The invention also provides the use of the compound or salt for the manufacture of a medicament for the treatment of pain, inflammation, rheumatoid arthritis, osteoarthritis, or a neurodegenerative disease.
摘要翻译：本发明提供式（I）化合物或其药学上可接受的盐，其中：A为C 1-6烷基，C 3-6环烷基，-CH 2 -R 6，-CHMe-R 7，-CMe 2 -R 7或任选取代的芳基; 其中当A是任选取代的芳基时，所述芳基任选地被1至3个可以相同或不同的取代基取代，所述取代基可以选自卤素，C 1-6烷基，-CF 3，C 1-4烷氧基，C 1-6烷氧基，氰基，NR8R9; 和吡啶基，其中吡啶基任选被一个甲基取代; R1是氯，氟，-CF3，氰基或C1-6烷基; R2，R3和R5独立地是氢，氟，氯，-CF3，氰基或C1-6烷基，使得R2，R3和R5中的至少一个不是氢; R4是氢。这些化合物和盐被认为是P2X7受体拮抗剂。本发明还提供了化合物或盐在制备用于治疗疼痛，炎症，类风湿性关节炎，骨关节炎或神经变性疾病的药物中的用途。

8. 发明申请

WO2008138876A1 PYRAZOLE DERIVATIVES AS P2X7 MODULATORS 审中-公开
标题翻译：作为P2X7调节剂的吡唑衍生物
公开(公告)号：WO2008138876A1
公开(公告)日：2008-11-20
申请号：PCT/EP2008/055724
申请日：2008-05-08
申请人： GLAXO GROUP LIMITED , BESWICK, Paul John , CHAMBERS, Laura Jane , CHESSELL, Iain Patrick , DAVIES, David John , DEMONT, Emmanuel Hubert , GLEAVE, Robert James , LIVERMORE, David George Hubert , THEOBALD, Pamela Joan , VIMAL, Mythily , WALTER, Daryl Simon
发明人： BESWICK, Paul John , CHAMBERS, Laura Jane , CHESSELL, Iain Patrick , DAVIES, David John , DEMONT, Emmanuel Hubert , GLEAVE, Robert James , LIVERMORE, David George Hubert , THEOBALD, Pamela Joan , VIMAL, Mythily , WALTER, Daryl Simon
IPC分类号： C07D231/12
CPC分类号： C07D231/12 , C07D401/04 , C07D401/06 , C07D403/04 , C07D403/06 , C07D403/10 , C07D405/04 , C07D405/12 , C07D417/04 , C07D417/06 , C07D471/08
摘要： The present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof: The pyrazole derivatives of formula (I) or salts thereof modulate P2X7 receptor function and are capable of antagonizing the effects of ATP at the P2X7 receptor (P2X7 receptor antagonists). The invention also relates to the use of such compounds or salts, or pharmaceutical compositions thereof, in the treatment or prevention of disorders / diseases mediated by the P2X7 receptor, for example pain, inflammation or a neurodegenerative disease.
摘要翻译：本发明涉及式（I）化合物或其药学上可接受的盐：式（I）的吡唑衍生物或其盐调节P2X7受体功能，并且能够拮抗ATP在P2X7受体（P2X7受体）拮抗剂）。本发明还涉及这些化合物或其盐或其药物组合物在治疗或预防P2X7受体介导的疾病/疾病中的用途，例如疼痛，炎症或神经变性疾病。

9. 发明申请

WO2008116814A1 PYRROLE AND ISOINDOLE CARBOXAMIDE DERIVATIVES AS P2X7 MODULATORS 审中-公开
标题翻译： PYRROLE和ISOINDOLE CARBOXAMIDE衍生物作为P2X7调节剂
公开(公告)号：WO2008116814A1
公开(公告)日：2008-10-02
申请号：PCT/EP2008/053343
申请日：2008-03-20
申请人： GLAXO GROUP LIMITED , GLEAVE, Robert, James , LIVERMORE, David, George, Hubert , WALTER, Daryl, Simon
发明人： GLEAVE, Robert, James , LIVERMORE, David, George, Hubert , WALTER, Daryl, Simon
IPC分类号： C07D207/38 , C07D209/46 , A61K31/4015 , A61K31/4035 , A61P29/00 , A61P25/28
CPC分类号： C07D207/38 , C07D209/46
摘要： The present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof: wherein: R 2 represents hydrogen, halogen, C 1-6 alkyl, C 6-10 arylmethyl-, C 2-6 alkenyl, C 2-6 alkynyl or C 3-6 cycloalkylmethyl-; and any of said C 1-6 alkyl, C 6-10 arylmethyl-, C 2-6 alkenyl, C 2-6 alkynyl or C 3-6 cycloalkylmethyl- is optionally substituted with 1, 2 or 3 halogen atoms; and R 3 represents hydrogen, fluorine or methyl; or R 2 and R 3 together with the carbon atoms to which they are attached form a benzene ring optionally substituted with 1, 2 or 3 substituents, which may be the same or different, selected from the group consisting of C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl. The compounds or salts modulate P2X7 receptor function and are capable of antagonizing the effects of ATP at the P2X7 receptor. The invention also provides the use of such compounds or salts, or pharmaceutical compositions thereof, in the treatment of disorders mediated by the P2X7 receptor, for example pain, inflammation or neurodegeneration.
摘要翻译：本发明涉及式（I）化合物或其药学上可接受的盐：其中：R 2表示氢，卤素，C 1-6烷基，C 1〜 C 3-6亚芳基甲基 - ，C 2-6亚烯基，C 2-6亚炔基或C 3-6环烷基甲基 - ; 和任何所述C 1-6烷基，C 6-10-10芳基甲基 - ，C 2-6 - 烯基，C 2 - 6个炔基或C 3-6环烷基甲基 - 任选被1,2或3个卤素原子取代; R 3表示氢，氟或甲基; 或R 2和R 3与它们所连接的碳原子一起形成任选被1,2或3个取代基取代的苯环，其可以相同或不同的，选自C 1-6烷基，C 2-6亚烯基和C 2-6亚炔基。化合物或盐调节P2X7受体功能，并能够拮抗ATP在P2X7受体上的作用。本发明还提供了这些化合物或其盐或其药物组合物在治疗由P2X7受体介导的病症中的用途，例如疼痛，炎症或神经变性。

10. 发明申请

WO2004094430A1 TRICYCLIC INDOLE DERIVATIVES AND THEIR USE IN THE TREATMENT OF ALZHEIMER’S DISEASE 审中-公开
标题翻译：三氯吲哚衍生物及其在治疗阿尔茨海默病中的应用
公开(公告)号：WO2004094430A1
公开(公告)日：2004-11-04
申请号：PCT/EP2004/004244
申请日：2004-04-21
申请人： GLAXO GROUP LIMITED , DEMONT, Emmanuel, Hubert , REDSHAW, Sally , WALTER, Daryl, Simon
发明人： DEMONT, Emmanuel, Hubert , REDSHAW, Sally , WALTER, Daryl, Simon
IPC分类号： C07D487/14
CPC分类号： C07D487/06 , C07D513/06
摘要： The present invention relates to novel hydroxyethylamine compounds having Asp2 (β-secretase, BACE1 or Memapsin) inhibitory activity, processes for their preparation, to compositions containing them and to their use in the treatment of diseases characterised by elevated β- amyloid levels or β-amyloid deposits, particularly Alzheimer's disease.
摘要翻译：本发明涉及具有Asp2（β-分泌酶，BACE1或Memapsin）抑制活性的新型羟乙基胺化合物，其制备方法，含有它们的组合物及其用于治疗以β-淀粉样蛋白水平升高或β- 淀粉样沉积物，特别是阿尔茨海默氏病。

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