公开(公告)号：CA2704698A1

公开(公告)日：2009-05-14

申请号：CA2704698

申请日：2008-11-03

Applicant: SCHERING CORP

Inventor： GREENLEE WILLIAM J ,  ZHU ZHAONING ,  ASBEROM THEODROS ,  HUANG XIANHAI ,  JOSIEN HUBERT B

IPC: C07D487/10 ,  C07D487/20 ,  C07D493/20 ,  C07D495/20 ,  C07D498/10 ,  C07D498/20 ,  C07D498/22 ,  C07F7/08 ,  C07F9/6571

Abstract: This invention provides novel compounds that are modulators of gamma secretase. The compounds have the formula (I). Also disclosed are methods of modulating gamma secretase activity and methods of treating Alzheimer's Disease using the compounds of formula (I).

公开(公告)号：CA2693216A1

公开(公告)日：2009-01-22

申请号：CA2693216

申请日：2008-07-15

Applicant: SCHERING CORP

Inventor： SASIKUMAR THAVALAKULAMGARA K ,  BURNETT DUANE A ,  ASBEROM THEODROS ,  WU WEN-LIAN ,  LI HONGMEI ,  XU RUO ,  JOSIEN HUBERT B

IPC: C07D491/04 ,  A61K31/35 ,  A61K31/519 ,  A61K31/54 ,  A61K31/542 ,  C07D493/04 ,  C07D513/04 ,  C07D513/14

Abstract: Disclosed are novel gamma secretase inhibitors of the formula (I): or a pharmaceutically acceptable salt, solvate, or ester thereof, wherein L1' n, X, Ar, Y, Z, Q, and Q1 are as defined herein. Also disclosed are methods for inhibiting gamma secretase, methods for treating Azheimer's disease, methods of treating one or more neurodegenerative diseases, and methods of inhibiting the deposition of amyloid protein (e.g., amyloid beta protein) in, on or around neurological tissue (e.g., the brain) using the compounds of formula 1Ø

公开(公告)号：AU2008276492A1

公开(公告)日：2009-01-22

申请号：AU2008276492

申请日：2008-07-15

Applicant: SCHERING CORP

Inventor： XU RUO ,  ASBEROM THEODROS ,  LI HONGMEI ,  WU WEN-LIAN ,  JOSIEN HUBERT B ,  BURNETT DUANE A ,  SASIKUMAR THAVALAKULAMGARA K

IPC: C07D491/04 ,  A61K31/35 ,  A61K31/519 ,  A61K31/54 ,  A61K31/542 ,  C07D493/04 ,  C07D513/04 ,  C07D513/14

Abstract: Disclosed are novel gamma secretase inhibitors of the formula (I): or a pharmaceutically acceptable salt, solvate, or ester thereof, wherein L1, n, X, Ar, Y, Z, Q, and Q1 are as defined herein. Also disclosed are methods for inhibiting gamma secretase, methods for treating Alzheimer's disease, methods of treating one or more neurodegenerative diseases, and methods of inhibiting the deposition of amyloid protein (e.g., amyloid beta protein) in, on or around neurological tissue (e.g., the brain) using the compounds of formula 1.0.

公开(公告)号：CL2008001303A1

公开(公告)日：2008-11-14

申请号：CL2008001303

申请日：2008-05-06

Applicant: SCHERING CORP

Inventor： M ,  ASBEROM THEODROS ,  GREENLEE WILLIAM J ,  SUN ZHONG-YUE ,  HUANG XIANHAI ,  ZHU ZHAOING ,  GALLO GIOCONDA ,  ZHU XIAOHONG

IPC: A61K31/4245 ,  A61K31/435 ,  A61P25/28 ,  C07D271/00 ,  C07D295/00 ,  C07D311/00 ,  C07D498/04 ,  C07D498/12

Abstract: Compuestos derivados de heterociclos, moduladores de gamma-secretasa; composición farmacéutica; kit farmacéutico; y uso en el tratamiento de la enfermedad de Alzheimer.

公开(公告)号：AU2003210865B2

公开(公告)日：2008-01-31

申请号：AU2003210865

申请日：2003-02-05

Applicant: PHARMACOPEIA INC ,  SCHERING CORP

Inventor： ASBEROM THEODROS ,  SMITH ELIZABETH M ,  PISSARNITSKI DMITRI A ,  CLADER JOHN W ,  GUO TAO ,  JOSIEN HUBERT B ,  HOBBS DOUGLAS W

IPC: C07D491/113 ,  A61K31/445 ,  A61K31/4535 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/4709 ,  A61K31/4725 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/541 ,  A61K31/55 ,  A61K31/551 ,  A61P25/18 ,  A61P25/28 ,  A61P43/00 ,  C07D211/96 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D405/14 ,  C07D409/12 ,  C07D413/12 ,  C07D413/14 ,  C07D417/14 ,  C07D471/10

Abstract: This invention discloses novel gamma secretase inhibitors of the formula: wherein: R 1 is a substituted aryl or substituted heteroaryl group; R 2 is an R 1 group, alkyl, -X(CO)Y, or alkylene-X(CO)Y wherein X and Y are as defined herein; each R 3 and each R 3A are independently H, or alkyl; R 11 is aryl, heteroaryl, alkyl, cycloalkyl, arylalkyl, arylcycloalkyl, heteroarylalkyl, heteroarylcycloalkyl, arylheterocycloalkyl, or alkoxyalkyl. Also disclosed is a method of treating Alzheimer's Disease using one or more compounds of the invention.

公开(公告)号：PE20071321A1

公开(公告)日：2007-12-29

申请号：PE2007000055

申请日：2007-01-18

Applicant: SCHERING CORP

Inventor： ASBEROM THEODROS ,  BARA THOMAS A ,  BENNETT CHAD E ,  BURNETT DUANE A ,  CAPLEN MARY ANN ,  CLADER JOHN W ,  DOLMALSKI MARTIN S ,  JOSIEN HUBERT B ,  KNUTSON CHAD E ,  LI HONGMEI ,  MCBRIAR MARK D ,  PISSARNITSKI DMITRI A ,  QIANG LI ,  RAJAGOPALAN MURALI ,  SASIKUMAR THAVALAKULAMGAR K ,  SU JING ,  TANG HAIQUN ,  WU WEN-LIAN ,  XU RUO ,  ZHAO ZHIQIANG ,  COLE DAVID J

IPC: A61K31/185 ,  A61K31/19 ,  A61K31/353 ,  A61K31/473 ,  A61K31/4738 ,  A61K31/4741

Abstract: SE REFIERE A UN COMPUESTO DE FORMULA I, DONDE X ES O, S, SO2, NR1, ENTRE OTROS; R1 ES H, ALQUILO; R2, R3 Y R4 SON CADA UNO H, ALQUILO, -CO-ALQUILO, COO-ALQUILO, ENTRE OTROS; Ar ES ARILO SUSTITUIDO O NO CON UNO O MAS L1, HETEROARILO SUSTITUIDO O NO CON UNO O MAS L1; L1 ES HALOGENO, ALQUILO, CN, CF3, -O-(ALQUILO C1-C6), ENTRE OTROS; n ES 0-3; m ES 0-3. SON COMPUESTOS PREFERIDOS: 1-(4-CLORO-BENCENSULFONIL)-5,8-DIFLUOR-1,2,3,4-TETRAHIDRO-NAFTALENO; TRANS-1-(4-CLOROBENCENSULFONILO)-2-ETIL-5,8-DIFLUOR-1,2,3,4-TETRAHIDRO-NAFTALENO; ENTRE OTROS. DICHOS COMPUESTOS INHIBEN LA GAMMA SECRETASA UTILES EN EL TRATAMIENTO DE ENFERMEDADES NEURODEGENERATIVAS

公开(公告)号：PL195027B1

公开(公告)日：2007-08-31

申请号：PL34111498

申请日：1998-11-23

Applicant: SCHERING CORP

Inventor： CHACKALAMANNIL SAMUEL ,  ASBEROM THEODROS ,  XIA YAN ,  DOLLER DARIO ,  CLASBY MARTIN C ,  CZARNIECKI MICHAEL F

IPC: C07D405/14 ,  C07D491/056 ,  A61K31/4184 ,  A61K31/423 ,  A61K31/427 ,  A61K31/44 ,  A61K31/443 ,  A61K31/4433 ,  A61K31/4545 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/4738 ,  A61K31/496 ,  A61K31/497 ,  A61K31/498 ,  A61K31/501 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/55 ,  A61P7/02 ,  A61P9/00 ,  A61P9/04 ,  A61P9/06 ,  A61P9/10 ,  A61P9/12 ,  A61P35/00 ,  A61P43/00 ,  C07D401/06 ,  C07D405/04 ,  C07D405/06 ,  C07D405/12 ,  C07D409/14 ,  C07D413/06 ,  C07D417/06 ,  C07D417/14 ,  C07D471/04 ,  C07D491/04 ,  C07D493/04 ,  C07D493/10

Abstract: Heterocyclic-substituted tricyclics of formula (I) or a pharmaceutically acceptable salt thereof, wherein: the single dotted line represents an optional double bond; the double dotted line represents an optional single bond; n is 0-2; Q is optionally substituted cycloalkyl, heterocycloalkyl, aryl or heteroaryl; Het is an optionally substituted mono-, bi- or tricyclic heteroaromatic group; B is -(CH2)n3-, wherein n3 is 0-5, -CH2-O-, -CH2S-, -CH2-NR -, -C(O)NR -. -NR C(O)-, (a), optionally substituted alkenyl or optionally substituted alkynyl; X is -O- or -NR - when the double dotted line represents a single bond, or X is -OH or -NHR when the bond is absent; Y is =O, =S, (H, H), (H, OH) or (H, C1-C6 alkoxy) when the double dotted line represents a single bond, or when the bond is absent, Y is =O, (H, H), (H, OH), (H, SH) or (H, C1-C6 alkoxy); R is absent when the double dotted line represents a single bond and is H, -NR R , or -OR when the bond is absent; or Y is (A) or (B) and R is H or C1-C6 alkyl; are disclosed, as well as pharmaceutical compositions containing them and a method of treating diseases associated with thrombosis, atherosclerosis, restenosis, hypertension, angina pectoris, arrhythmia, heart failure, and cancer by administering said compounds.

公开(公告)号：AU2007207481A1

公开(公告)日：2007-07-26

申请号：AU2007207481

申请日：2007-01-18

Applicant: SCHERING CORP

Inventor： CLADER JOHN W ,  RAJAGOPALAN MURALI ,  ZHAO ZHIQIANG ,  TANG HAIQUN ,  BENNETT CHAD E ,  WU WEN-LIAN ,  XU RUO ,  ASBEROM THEODROS ,  JOSIEN HUBERT B ,  MCBRIAR MARK D ,  LI HONGMEI ,  BARA THOMAS ,  PISSARNITSKI DMITRI A ,  SASIKUMAR THAVALAKULAMGAR K ,  BURNETT DUANE A ,  SU JING ,  QIANG LI ,  KNUTSON CHAD E ,  CAPLEN MARY ANN ,  COLE DAVID J ,  DOMALSKI MARTIN S

IPC: C07D311/22 ,  C07D311/80 ,  C07D311/92 ,  C07D311/94 ,  C07D313/08 ,  C07D335/06

Abstract: This invention discloses novel gamma secretase inhibitors of the formula: R2 and R3, or R2 and R4, or R3 and R4, together with the atoms to which they are bound, can form a fused cycloalkyl or fused heterocycloalkyl ring. The cycloalkyl ring or the heterocycloalkyl ring can be optionally substituted with one or more substituents. One or more compounds of formula (I), or formulations comprising such compounds, may be useful, e.g. in treating Alzheimer's Disease.

公开(公告)号：PE20060165A1

公开(公告)日：2006-04-13

申请号：PE2005000380

申请日：2005-04-05

Applicant: SCHERING CORP

Inventor： ASBEROM THEODROS ,  CLADER JOHN W ,  JOSIEN HUBERT B ,  ZHAO ZHIQIANG ,  MCBRIAR MARK ,  PISSARNITSKI DMITRI A

IPC: A61K31/44 ,  A61P25/28 ,  C07D211/96 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D451/04 ,  C07D471/04 ,  C07D471/10 ,  C07D487/04 ,  C07D487/08

Abstract: SE REFIERE A COMPUESTOS QUE CONTIENEN UN GRUPO SULFONA DE FORMULA (I), EN DONDE R1 ES ARILO O HETEROARILO OPCIONALMENTE SUSTITUIDO POR UNO O MAS R5; R2 ES -(C0-C12)ALQUILEN-C(O)-Y, -(C0-C6)ALQUILEN-(C3-C6)CICLOALQUILEN-(C0-C6)ALQUILEN-C(O)-Y, -(C0-C12)ALQUILEN-S(O2)-Y, -(C0-C6)ALQUILEN-(C3-C6)CICLOALQUILEN-(C0-C6)ALQUILEN-S(O2)-Y, ENTRE OTROS, DONDE EL ALQUILEN O CICLOALQUILEN ESTAN OPCIONALMENTE SUSTITUIDO POR HIDROXI; Y ES a), b), c), d), ENTRE OTROS; CADA R3 DE (R3)2 SE SELECCIONA DE H, OH, ALQUILO O ACILO(C1-C6); LA PARTE (R3)2 JUNTO AL C ANULAR DEFINE UN CARBONILO, SOLO SI CUANDO m ES MAYOR QUE 1, A LO SUMO UN CARBONILO ESTA PRESENTE; CADA R3A Y R3B ES INDEPENDIENTEMENTE H O ALQUILO(C1-C6); R5 ES HALO, OH, CF3 Y -0-(C1-C6). TAMBIEN SE REFIERE A UNA COMPOSICION FARMACEUTICA. ESTOS COMPUESTOS SON INHIBIDORES DE LA SECRETASA GAMMA Y SON UTILES EN EL TRATAMIENTO DEL MAL DE ALZHEIMER

公开(公告)号：AU2002324582B2

公开(公告)日：2006-01-05

申请号：AU2002324582

申请日：2002-08-01

Applicant: SCHERING CORP

Inventor： PISSARNITSKI DMITRI A ,  ASBEROM THEODROS ,  GUZIK HENRY S ,  JOSIEN HUBERT B

IPC: C07D487/04 ,  A61K31/437 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/496 ,  A61K31/5377 ,  A61P9/10 ,  A61P25/00 ,  A61P25/28 ,  A61P43/00 ,  C07D215/58 ,  C07D401/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07D471/04 ,  C07D487/08 ,  C07D521/00

Abstract: This invention discloses novel gamma secretase inhibitors of the formula: wherein: R1 is a substituted aryl or substituted heteroaryl group; R2 is an R1 group, alkyl, -X(CO)Y, -(CR32)1-4X(CO)Y; each R3A is independently H or alkyl; X is -O-, -NH, or -N-alkyl; and Y is -NR6R7, or -N(R3)(CH2)2-6NR6R7. Also disclosed is a method of treating Alzheimer's Disease.