公开(公告)号：WO2006098961A3

公开(公告)日：2007-03-22

申请号：PCT/US2006008145

申请日：2006-03-07

Applicant: SCHERING CORP ,  TAGAT JAYARAM R ,  GUZI TIMOTHY J ,  LABROLI MARC ,  POKER CORY ,  XIAO YUSHI ,  KEREKES ANGELA D ,  YU TAO ,  PALIWAL SUNIL ,  TSUI HON-CHUNG ,  SHIH NENG-YANG ,  MCCOMBIE STUART W ,  MADISON VINCENT S ,  LESBURG CHARLES A ,  DUCA JOSE S

Inventor： TAGAT JAYARAM R ,  GUZI TIMOTHY J ,  LABROLI MARC ,  POKER CORY ,  XIAO YUSHI ,  KEREKES ANGELA D ,  YU TAO ,  PALIWAL SUNIL ,  TSUI HON-CHUNG ,  SHIH NENG-YANG ,  MCCOMBIE STUART W ,  MADISON VINCENT S ,  LESBURG CHARLES A ,  DUCA JOSE S

IPC: C07D495/04 ,  A61K31/4365 ,  A61K31/4545 ,  A61K31/4709 ,  A61K31/496 ,  A61K31/497 ,  A61K31/498 ,  A61K31/53 ,  A61K31/5377 ,  A61P35/00 ,  C07D495/14 ,  C07D495/20 ,  C07D513/04

CPC classification number: C07D519/00 ,  C07D493/10 ,  C07D495/04 ,  C07D495/06 ,  C07D495/14 ,  C07D495/20 ,  C07D513/04

Abstract: The present invention provides compounds of Formula (I) (wherein R 1 , R 3 , X, W, Z and ring Y are as defined herein). The present invention also provides compositions comprising these compounds that are useful for treating cellular proliferative diseases or disorders associated with KSP kinesin activity and for inhibiting KSP kinesin activity.

Abstract translation: 本发明提供式（I）（其中R 1，R 3，X，W，Z和环Y如本文所定义）的化合物。 本发明还提供了包含这些化合物的组合物，其可用于治疗与KSP驱动蛋白活性相关的细胞增殖性疾病或病症并抑制KSP驱动蛋白活性。

公开(公告)号：WO9805292A3

公开(公告)日：1998-04-02

申请号：PCT/US9713383

申请日：1997-08-06

Applicant: SCHERING CORP

Inventor： LOWE DEREK B ,  CHANG WEI K ,  KOZLOWSKI JOSEPH A ,  BERGER JOEL G ,  MCQUADE ROBERT ,  BARNETT ALLEN ,  SHERLOCK MARGARET ,  TOM WING ,  DUGAR SUNDEEP ,  CHEN LIAN-YONG ,  CLADER JOHN W ,  CHACKALAMANNIL SAMUEL ,  WANG YUGUANG ,  MCCOMBIE STUART W ,  TAGAT JAYARAM R ,  VICE SUSAN F ,  VACCARO WAYNE D ,  GREEN MICHAEL J ,  BROWNE MARGARET E ,  ASBEROM THEODROS ,  BOYLE CRAIG D ,  JOSIEN HUBERT B

IPC: C07D211/58 ,  A61K31/00 ,  A61K31/435 ,  A61K31/4427 ,  A61K31/443 ,  A61K31/4433 ,  A61K31/445 ,  A61K31/4465 ,  A61K31/4523 ,  A61K31/4545 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/495 ,  A61K31/496 ,  A61K31/50 ,  A61K31/501 ,  A61K45/00 ,  A61P25/28 ,  C07D211/24 ,  C07D211/32 ,  C07D211/96 ,  C07D239/34 ,  C07D257/04 ,  C07D295/02 ,  C07D295/03 ,  C07D295/084 ,  C07D295/088 ,  C07D295/096 ,  C07D295/112 ,  C07D295/116 ,  C07D295/125 ,  C07D295/13 ,  C07D295/135 ,  C07D295/145 ,  C07D295/15 ,  C07D401/04 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D405/12 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  A61K

CPC classification number: C07D405/14 ,  C07C2601/14 ,  C07D211/24 ,  C07D211/32 ,  C07D239/34 ,  C07D257/04 ,  C07D295/03 ,  C07D295/088 ,  C07D295/092 ,  C07D295/096 ,  C07D295/112 ,  C07D295/116 ,  C07D295/125 ,  C07D295/13 ,  C07D295/135 ,  C07D295/145 ,  C07D295/15 ,  C07D405/12 ,  C07D409/14

Abstract: Di-N-substituted piperazine or 1,4 di-substituted piperidine compounds in accordance with formula I (including all isomers, salts, esters, and solvates) wherein R, R?1, R2, R3, R4, R21, R27, R28¿, X, Y and Z as defined herein are muscarinic antagonists useful for treating cognitive disorders such as Alzheimer's disease. Pharmaceutical compositions and methods of preparation are also disclosed. Also disclosed are synergistic combinations of compounds of the above formula with acetylcholinesterase inhibitors.

Abstract translation: 根据式I的二-N-取代哌嗪或1,4-二取代哌嗪化合物（包括所有异构体，盐，酯和溶剂合物），其中R，R 1，R 2，R 3，R 4，R 21，R 27，R 28，X Y和Z如本文所定义的是可用于治疗认知障碍如阿尔茨海默氏病的毒蕈碱拮抗剂。 还公开了药物组合物和制备方法。 还公开了上式化合物与乙酰胆碱酯酶抑制剂的协同组合。

公开(公告)号：JP2008024714A

公开(公告)日：2008-02-07

申请号：JP2007233458

申请日：2007-09-07

Applicant: Schering Corp ,  シェーリング コーポレイションSchering Corporation

Inventor： LOWE DEREK ,  WEI CHANG ,  KOZLOWSKI JOSEPH ,  BERGER JOEL G ,  MCQUADE ROBERT ,  BARNETT ALLEN ,  SCHERLOCK MARGARET ,  TOM WING ,  DUGAR SUNDEEP ,  CHEN LIAN-YONG ,  CLADER JOHN W ,  CHACKALAMANNIL SAMUEL ,  WANG YUGUANG ,  MCCOMBIE STUART W ,  TAGAT JAYARAM R ,  VICE SUSAN F ,  WAYNE VACCARO ,  GREEN MICHAEL J ,  BROWNE MARGARET E ,  ASBEROM THEODROS

IPC: C07D211/20 ,  C07D295/08 ,  A61K31/335 ,  A61K31/357 ,  A61K31/36 ,  A61K31/365 ,  A61K31/4427 ,  A61K31/443 ,  A61K31/445 ,  A61K31/4468 ,  A61K31/451 ,  A61K31/495 ,  A61K31/496 ,  A61K31/497 ,  A61K31/501 ,  A61K31/505 ,  A61K31/506 ,  A61K31/535 ,  A61K31/5375 ,  A61K31/5377 ,  A61K31/549 ,  A61P25/00 ,  A61P25/28 ,  C07D211/14 ,  C07D211/22 ,  C07D211/24 ,  C07D211/26 ,  C07D211/32 ,  C07D211/58 ,  C07D211/62 ,  C07D213/65 ,  C07D213/70 ,  C07D233/84 ,  C07D237/10 ,  C07D239/34 ,  C07D241/04 ,  C07D241/18 ,  C07D257/04 ,  C07D263/58 ,  C07D271/06 ,  C07D277/20 ,  C07D277/34 ,  C07D285/34 ,  C07D295/02 ,  C07D295/03 ,  C07D295/084 ,  C07D295/088 ,  C07D295/096 ,  C07D295/112 ,  C07D295/116 ,  C07D295/12 ,  C07D295/125 ,  C07D295/13 ,  C07D295/135 ,  C07D295/14 ,  C07D295/145 ,  C07D295/15 ,  C07D307/33 ,  C07D309/12 ,  C07D317/28 ,  C07D317/62 ,  C07D333/20 ,  C07D335/02 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  C07D409/14

CPC classification number: C07D211/20 ,  C07C2601/14 ,  C07D211/22 ,  C07D211/24 ,  C07D211/32 ,  C07D211/58 ,  C07D213/643 ,  C07D213/65 ,  C07D213/68 ,  C07D237/14 ,  C07D239/34 ,  C07D239/38 ,  C07D257/04 ,  C07D277/34 ,  C07D295/03 ,  C07D295/088 ,  C07D295/092 ,  C07D295/096 ,  C07D295/112 ,  C07D295/116 ,  C07D295/125 ,  C07D295/13 ,  C07D295/135 ,  C07D295/145 ,  C07D295/15 ,  C07D295/26 ,  C07D307/33 ,  C07D333/20 ,  C07D335/02 ,  C07D405/12 ,  C07D405/14 ,  C07D409/14

Abstract: PROBLEM TO BE SOLVED: To provide muscarinic antagonists useful for treating cognitive disorders. SOLUTION: The di-N-substituted piperidine compound or 1,4-di-substituted piperazine compound of formula (I) (R, R 1 , R 2 , R 3 , R 4 , R 21 , R 27 , R 28 , X, Y, and Z are particularly defined) (including all isomers, salts, esters, and solvates) are muscarinic antagonists useful for treating cognitive disorders such as Alzheimer's disease. Pharmaceutical compositions and methods of preparation are also disclosed. Also disclosed are synergistic combinations of compounds of the above formula or other compounds capable of enhancing acetylcholine release with acetylcholinesterase inhibitors. COPYRIGHT: (C)2008,JPO&INPIT

Abstract translation: 要解决的问题：提供可用于治疗认知障碍的毒蕈碱拮抗剂。 解决方案：式（I）的二-N-取代的哌啶化合物或1,4-二取代哌嗪化合物（R，R 1，R 2，R 2， ，R 3 ，R 4 ，R 21 ，R SP SP 27， ，X，Y和Z特别定义）（包括所有异构体，盐，酯和溶剂合物）是可用于治疗认知障碍如阿尔茨海默氏病的毒蕈碱拮抗剂。 还公开了药物组合物和制备方法。 还公开了上述化合物或能够与乙酰胆碱酯酶抑制剂一起增强乙酰胆碱释放的其它化合物的协同组合。 版权所有（C）2008，JPO＆INPIT

公开(公告)号：JP2011219493A

公开(公告)日：2011-11-04

申请号：JP2011151208

申请日：2011-07-07

Applicant: Schering Corp ,  シェーリング コーポレイションSchering Corporation

Inventor： BAROUDY BAHIGE M ,  CLADER JOHN W ,  JOSIEN HUBERT B ,  MCCOMBIE STUART W ,  MCKITTRICK BRIAN A ,  MILLER MICHAEL W ,  NEUSTADT BERNARD R ,  PALANI ANANDAN ,  STEENSMA RUO ,  TAGAT JAYARAM R ,  VICE SUSAN F ,  LAUGHLIN MARK A

IPC: C07D211/58 ,  A61K31/4468 ,  A61K31/4523 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/497 ,  A61K31/506 ,  A61P1/00 ,  A61P11/06 ,  A61P17/00 ,  A61P17/04 ,  A61P17/06 ,  A61P19/00 ,  A61P19/02 ,  A61P25/00 ,  A61P29/00 ,  A61P31/12 ,  A61P31/18 ,  A61P37/00 ,  A61P37/06 ,  A61P37/08 ,  A61P43/00 ,  C07D401/14 ,  C07D405/14 ,  C07D413/14 ,  C07D417/14

CPC classification number: C07D413/14 ,  C07D211/58 ,  C07D401/14 ,  C07D417/14

Abstract: PROBLEM TO BE SOLVED: To provide piperazine derivatives useful as selective CCR5 antagonists, pharmaceutical compositions containing compounds thereof, and methods of treatment using the compounds.SOLUTION: There are provided: the method, as for the treatment of HIV, comprising administering to a human in need of such treatment an effective amount of a CCR5 antagonist; the pharmaceutical composition for the treatment of HIV comprising an effective amount of a CCR5 antagonist in combination with a pharmaceutically acceptable carrier; and the pharmaceutical composition for the treatment of solid organ transplant rejection, graft vs host disease, arthritis, rheumatoid arthritis, inflammatory bowel disease, atopic dermatitis, psoriasis, asthma, allergies, or multiple sclerosis comprising an effective amount of a CCR5 antagonist in combination with a pharmaceutically acceptable carrier.

Abstract translation: 待解决的问题：提供可用作选择性CCR5拮抗剂的哌嗪衍生物，含有其化合物的药物组合物，以及使用该化合物的治疗方法。 提供了：用于治疗HIV的方法，包括向需要这种治疗的人施用有效量的CCR5拮抗剂; 用于治疗HIV的药物组合物，其包含与药学上可接受的载体组合的有效量的CCR5拮抗剂; 以及用于治疗实体器官移植排斥，移植物抗宿主病，关节炎，类风湿性关节炎，炎性肠病，特应性皮炎，牛皮癣，哮喘，过敏或多发性硬化的药物组合物，其包含有效量的CCR5拮抗剂与 药学上可接受的载体。 版权所有（C）2012，JPO＆INPIT

公开(公告)号：CZ301161B6

公开(公告)日：2009-11-18

申请号：CZ20013941

申请日：2000-05-01

Applicant: SCHERING CORP

Inventor： BAROUDY BAHIGE M ,  CLADER JOHN W ,  JOSIEN HUBERT B ,  MCCOMBIE STUART W ,  MCKITTRICK BRIAN A ,  MILLER MICHAEL W ,  NEUSTADT BERNARD R ,  PALANI ANANDAN ,  STEENSMA RUO ,  TAGAT JAYARAM R ,  VICE SUSAN F ,  LAUGHLIN MARK A

IPC: C07D211/58 ,  A61K31/4468 ,  A61K31/4523 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/497 ,  A61K31/506 ,  A61P1/00 ,  A61P11/06 ,  A61P17/00 ,  A61P17/06 ,  A61P19/00 ,  A61P19/02 ,  A61P29/00 ,  A61P31/12 ,  A61P31/18 ,  A61P37/00 ,  A61P37/06 ,  A61P37/08 ,  C07D401/14 ,  C07D405/14 ,  C07D413/14 ,  C07D417/14

Abstract: Piperidinopiperidylové deriváty užitecné jako CCR5 antagonisté obecného vzorce II nebo jejich farmaceuticky prijatelné sole, kde substituenty jsou uvedeny v nárocích, jejich použití pri výrobe farmaceutického prostredku pro lécbu HIV, odmítnutí transplantovaného pevného orgánu, odmítnutí štepu hostitelem, artritidy, kloubního revmatismu, zánetlivé choroby strev, atopické dermatitidy, lupénky, astmatu, alergií nebo roztroušené sklerózy. Nové farmaceutické prípravky obsahující tyto deriváty a kombinaci derivátu - CCR5 antagonistu podle predkládaného vynálezu v kombinaci s antivirálními cinidly užitecnými pro lécbu HIV nebo cinidly užitecnými pri lécbe zánetlivých chorob.

公开(公告)号：CA2336000C

公开(公告)日：2006-10-10

申请号：CA2336000

申请日：1999-06-28

Applicant: SCHERING CORP

Inventor： KOZLOWSKI JOSEPH A ,  MCCOMBIE STUART W ,  TAGAT JAYARAM R ,  VICE SUSAN F

IPC: C07D405/14 ,  A61K31/4427 ,  A61K31/443 ,  A61K31/4433 ,  A61K31/445 ,  A61K31/4545 ,  A61K31/495 ,  A61K31/496 ,  A61K31/50 ,  A61K31/501 ,  A61P25/28 ,  A61P43/00 ,  C07D401/12 ,  C07D401/14 ,  C07D409/12

Abstract: Heterocyclic derivatives of di-N-substituted piperazine or 1,4 di-substitute d piperidine compounds in accordance with formula (I) (including all isomers salts and solvates), wherein one of Y and Z is -N- an d the other is -N- or -CH-; X is -O-, -S-, -SO-, -SO2- or -CH2-; Q is (1), (2), (3); R is alkyl, cycloalkyl, optionally substituted aryl or heteroaryl; R1, R2 and R3 are H or alkyl; R4 is alkyl, cyclolalkyl or (4); R5 is H, alkyl, -C(O)alkyl, arylcarbonyl, -SO2alkyl, ary l- sulfonyl-C(O)Oalkyl, aryloxycarbonyl, -C(O)NH-alkyl or aryl-aminocarbonyl, wherein the aryl portion is optionally substituted; R6 i s H or alkyl; and R7 is H, alkyl, hydroxyalkyl or alkoxyalkyl; are muscarinic antagonists useful for treating cognitive disorders such as Alzheimer's disease. Pharmaceutical compositions and methods of treatment are also disclosed.

公开(公告)号：PE10122006A1

公开(公告)日：2006-10-03

申请号：PE0002102006

申请日：2006-02-21

Applicant: SCHERING CORP

Inventor： CHAN TZE-MING ,  COX KATHLEEN ,  FENG WENQING ,  MILLER MICHAEL W ,  WESTON DANIEL ,  MCCOMBIE STUART W

IPC: A61K31/496 ,  A61P31/18 ,  C07D401/06 ,  C07D401/14

CPC classification number: C07D211/96 ,  C07D401/06 ,  C07D401/14

Abstract: SE REFIERE A UN COMPUESTO DE FORMULA IA, DONDE R1 ES SELECCIONADO DE R9-FENILO, R9-PIRIDILO, R9-TIOFENILO, ENTRE OTROS; R2 ES H, ALQUILO; R3 ES H, ALQUILO, ALCOXIALQUIL-CICLOALQUILO, CICLOALQUILALQUIL-, ENTRE OTROS; R4, R5, R6 Y R7 SONCADA UNO H, ALQUILO; R8 ES A, B, C; R9 ES 1-3 SUSTITUYENTES SELECCIONADOS DE H, HALOGENO, ALQUILO, ALCOXI, -OCF3, -CN, ENTRE OTROS; R15 Y R16 SON CADA UNO ALQUILO, HALOGENO, -OH, -CF3, -O-ACILO, ENTRE OTROS; R17 ES H2N, O-ALQUILO, ENTRE OTROS. SON COMPUESTOS PREFERIDOS: D, E, ENTRE OTROS. SE REFIERE TAMBIEN A UNA COMPOSICION FARMACEUTICA Y A UNA PROCEDIMIENTO DE PREPARACION. DICHOS COMPUESTOS SON INHIBIDORES DE LOS RECEPTORES DE QUIMOCINA ESPECIALMENTE CCR5, QUE EM COMBINACION CON AGENTES ANTIVIRALES TALES COMO LAMIVUDINA, ZIDOVUDINA, ABACABIR, ENTRE OTROS, SON UTILES EN EL TRATAMIENTO DEL SIDA

公开(公告)号：CA2599899A1

公开(公告)日：2006-09-21

申请号：CA2599899

申请日：2006-03-07

Applicant: SCHERING CORP

Inventor： POKER CORY ,  XIAO YUSHI ,  TSUI HON-CHUNG ,  TAGAT JAYARAM R ,  DUCA JOSE S ,  GUZI TIMOTHY J ,  YU TAO ,  PALIWAL SUNIL ,  LESBURG CHARLES A ,  KEREKES ANGELA D ,  LABROLI MARC ,  MCCOMBIE STUART W ,  MADISON VINCENT S ,  SHIH NENG-YANG

IPC: C07D495/04 ,  A61K31/4365 ,  A61K31/4545 ,  A61K31/4709 ,  A61K31/496 ,  A61K31/497 ,  A61K31/498 ,  A61K31/53 ,  A61K31/5377 ,  A61P35/00 ,  C07D495/14 ,  C07D495/20 ,  C07D513/04

Abstract: The present invention provides compounds of Formula I (wherein R 1 , R 3 , X, W, Z and ring Y are as defined herein). The present invention also provides compositions comprising these compounds that are useful for treating cellular proliferative diseases or disorders associated with KSP kinesin activity and for inhibiting KSP kinesin activity.

公开(公告)号：PT1175402E

公开(公告)日：2005-11-30

申请号：PT00926487

申请日：2000-05-01

Applicant: SCHERING CORP

Inventor： CLADER JOHN W ,  MCCOMBIE STUART W ,  NEUSTADT BERNARD R ,  MCKITTRICK BRIAN A ,  TAGAT JAYARAM R ,  VICE SUSAN F ,  JOSIEN HUBERT B ,  LAUGHLIN MARK A ,  BAROUDY BAHIGE M ,  MILLER MICHAEL W ,  PALANI ANANDAN ,  STEENSMA RUO

IPC: A61K31/4468 ,  A61K31/4523 ,  A61K31/454 ,  A61K31/497 ,  A61K31/506 ,  A61P1/00 ,  A61P11/06 ,  A61P17/00 ,  A61P17/06 ,  A61P19/00 ,  A61P19/02 ,  A61P29/00 ,  A61P31/12 ,  A61P31/18 ,  A61P37/00 ,  A61P37/08 ,  C07D211/58 ,  C07D401/14 ,  C07D405/14 ,  C07D413/14 ,  C07D417/14

公开(公告)号：DK1175401T3

公开(公告)日：2005-11-14

申请号：DK00926486

申请日：2000-05-01

Applicant: SCHERING CORP

Inventor： BAROUDY BAHIGE M ,  CLADER JOHN W ,  MCCOMBIE STUART W ,  MCKITTRICK BRIAN A ,  MILLER MICHAEL W ,  NEUSTADT BERNARD R ,  PALANI ANANDAN ,  SMITH ELIZABETH M ,  STEENSMA RUO ,  TAGAT JAYARAM R ,  VICE SUSAN F ,  LAUGHLIN MARK A ,  GILBERT ERIC ,  LABROLI MARC A ,  JOSIEN HUBERT B

IPC: C07D401/04 ,  A61K31/496 ,  A61K31/497 ,  A61K31/506 ,  A61P1/04 ,  A61P11/06 ,  A61P17/00 ,  A61P17/06 ,  A61P19/00 ,  A61P19/02 ,  A61P25/28 ,  A61P29/00 ,  A61P31/12 ,  A61P31/18 ,  A61P37/00 ,  A61P37/08 ,  A61P43/00 ,  C07D211/58 ,  C07D401/06 ,  C07D401/10 ,  C07D401/14 ,  C07D405/12 ,  C07D409/06 ,  C07D409/14 ,  C07D413/06 ,  C07D413/14 ,  G01F1/46

Abstract: The use is described of CCR5 antagonists of formula (I) or a pharmaceutically acceptable salt thereof, wherein: R is optionally substituted phenyl, pyridyl, thiophenyl or naphthyl; R 1 is hydrogen or alkyl; R 2 is substituted phenyl, substituted heteroaryl, naphthyl, fluorenyl, diphenylmethyl or optionally substituted phenyl- or heteroaryl-alkyl; R 3 is hydrogen, alkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, or optionally substituted phenyl, phenylalkyl, naphthyl, naphthylalkyl, heteroaryl or heteroarylalkyl; R 4 , R 5 and R 7 are hydrogen or alkyl; R 6 is hydrogen, alkyl or alkenyl; for the treatment of HIV, solid organ transplant rejection, graft v. host disease, arthritis, rheumatoid arthritis, inflammatory bowel disease, atopic dermatitis, psoriasis, asthma, allergies or multiple sclerosis, as well as novel compounds, pharmaceutical compositions comprising them, and the combination of CCR5 antagonists of the invention in combination with antiviral agents useful in the treatment of HIV or agents useful in the treatment of inflammatory diseases.