公开(公告)号：WO2009008980A2

公开(公告)日：2009-01-15

申请号：PCT/US2008008192

申请日：2008-07-01

Applicant: SCHERING CORP ,  WU WEN-LIAN ,  BARA THOMAS A ,  BURNETT DUANE A ,  CLADER JOHN W ,  DOMALSKI MARTIN S ,  JIN YAN ,  JOSIEN HUBERT B ,  LI HONGMEI ,  LIANG XIAN ,  PISSARNITSKI DMITRI A ,  SASIKUMAR THAVALAKULAMGARA K ,  WONG JESSE K ,  XU RUO ,  ZHAO ZHIQIANG ,  MCNAMARA PAUL

Inventor： WU WEN-LIAN ,  BARA THOMAS A ,  BURNETT DUANE A ,  CLADER JOHN W ,  DOMALSKI MARTIN S ,  JIN YAN ,  JOSIEN HUBERT B ,  LI HONGMEI ,  LIANG XIAN ,  PISSARNITSKI DMITRI A ,  SASIKUMAR THAVALAKULAMGARA K ,  WONG JESSE K ,  XU RUO ,  ZHAO ZHIQIANG ,  MCNAMARA PAUL

IPC: C07D311/78 ,  A61K31/35 ,  A61K31/352 ,  A61P25/28 ,  C07D407/12 ,  C07D493/04

CPC classification number: C07D493/04 ,  C07D311/78 ,  C07D407/12

Abstract: Disclosed are novel gamma secretase inhibitors of the formula. Also disclosed are methods of inhibiting gamma-secretase, methods of treating neurodegenerative diseases, and methods of treating Alzheimer's Disease. Also disclosed are processes for preparing alkenes in one reaction step using a mixture of an aldehyde (or ketone) and an alkyl substituted with two electron withdrawing groups, and reacting the mixture with: (a) a sulfonyl halide (e.g., a sulfonyl chloride) and a basic tertiary amine, or, (b) a sulfonyl anhydride and a basic amine, or (c) an aryl-C(O)-halide and a basic tertiary amine, or (d) an aryl-C(O)-O-C(O)-aryl and a basic tertiary amine, or (e) an heteroaryl-C(O)-halide and a basic tertiary amine, or (f) a heteroaryl-C(O)-O-C(O)-heteroaryl and a basic tertiary amine.

Abstract translation: 公开了下式的新型γ分泌酶抑制剂。 还公开了抑制γ-分泌酶的方法，治疗神经退行性疾病的方法以及治疗阿尔茨海默氏病的方法。 还公开了使用醛（或酮）和被两个吸电子基团取代的烷基的混合物在一个反应​​步骤中制备烯烃的方法，并使该混合物与以下物质反应：（a）磺酰卤（例如磺酰氯） （b）磺酰基酸酐和碱性胺，或（c）芳基-C（O） - 卤化物和碱性叔胺，或（d）芳基-C（O） - OC（O） - 芳基和碱性叔胺，或（e）杂芳基-C（O） - 卤化物和碱性叔胺，或（f）杂芳基-C（O）-OC（O） - 杂芳基和 一种碱性叔胺。

公开(公告)号：WO2006004880A3

公开(公告)日：2007-03-08

申请号：PCT/US2005023187

申请日：2005-06-28

Applicant: SCHERING CORP ,  JOSIEN HUBERT B ,  CLADER JOHN W ,  BARA THOMAS A ,  XU RUO ,  LI HONGMEI ,  PISSARNITSKI DMITRI ,  ZHAO ZHIQIANG

Inventor： JOSIEN HUBERT B ,  CLADER JOHN W ,  BARA THOMAS A ,  XU RUO ,  LI HONGMEI ,  PISSARNITSKI DMITRI ,  ZHAO ZHIQIANG

IPC: C07D265/30 ,  A61K31/5377 ,  A61P25/28 ,  C07D413/12 ,  C07D451/02 ,  C07D487/08

CPC classification number: C07D265/30 ,  C07D413/12 ,  C07D451/02 ,  C07D487/08

Abstract: This invention discloses novel gamma secretase inhibitors of the formula I: wherein: L is -O- , -N(R 6 )-, -S-, -S(O)-, or -S(O 2 )-; R 1 is selected from the group consisting of aryl and heteroaryl; R 2 is selected from the group consisting of alkyl, -C(O)-Y, -X-C(O)-Y, -alkylene-X-C(O)-Y, -alkylene-C(O)-Y, -alkylene-cycloalkylene-X-C(O)-Y, -alkylene-cycloalkylene-C(O)-Y, -cycloalkylene-alkylene-X-C(O)-Y, -cycloalkylene-alkylene-C(O)-Y, -cycloalkylene-X-C(O)-Y, -cycloalkylene-C(O)-Y, -alkylene-cycloalkylene-alkylene-X-C(O)-Y, -alkylene-cycloalkylene-alkylene-C(O)-Y, aryl, and heteroaryl; R 3 is selected from the group consisting of aryl, heteroaryl, alkyl, cycloalkyl, arylalkyl, arylcycloalkyl, heteroarylalkyl, heteroarylcycloalkyl, arylheterocycloalkyl, and alkoxyalkyl; each R 4 and R 5 is independently selected from the group consisting of H and alkyl; and Y is selected from the group consisting of -NR 8 R 9 , -N(R 6 )-(CH 2 ) b -NR 8 R 9 , aryl, heteroaryl, alkyl, cycloalkyl, arylalkyl, arylcycloalkyl, heteroarylalkyl, heteroarylcycloalkyl, and arylheterocycloalkyl; or Y is selected from the group consisting of Formula II and Formula III: One or more compounds of formula I, or formulations comprising such compounds, may be useful, e.g. in treating Alzheimer's Disease.

Abstract translation: 本发明公开了式I的新型γ分泌酶抑制剂：其中：L是-O-，-N（R 6） - ， - S - ， - S（O） - 或-S（ 0 _{2 ） - ; R 1选自芳基和杂芳基; R 2选自烷基，-C（O）-Y，-XC（O）-Y， - 亚烷基-XC（O）-Y， - 亚烷基-C（O ）-Y-亚烷基 - 亚环烷基-OC（O）-Y-亚烷基 - 亚环烷基-C（O）-Y-亚烷基 - 亚烷基-OC（O）-Y-亚烷基 - 亚烷基-C（O） Y（ - ）亚环烷基-C（O）-Y-亚烷基-C（O）-Y-亚烷基 - 亚环烷基亚烷基-XC（O）-Y-亚烷基 - 亚环烷基 - 亚烷基-C（O）-Y， 芳基和杂芳基; R 3选自芳基，杂芳基，烷基，环烷基，芳基烷基，芳基环烷基，杂芳基烷基，杂芳基环烷基，芳基杂环烷基和烷氧基烷基; 每个R 4和R 5独立地选自H和烷基; 并且Y选自-NR 8 R 9，-N（R 6） - （CH 2） 芳基，杂芳基，烷基，环烷基，芳基烷基，芳基环烷基，杂芳基烷基，杂芳基环烷基和芳基杂环烷基 ; 或Y选自式II和式III的化合物：一种或多种式I化合物或包含该化合物的制剂可用于，例如， 治疗阿尔茨海默病。}

公开(公告)号：HK1099300A1

公开(公告)日：2007-08-10

申请号：HK07106506

申请日：2007-06-15

Applicant: SCHERING CORP

Inventor： JOSIEN HUBERT B ,  CLADER JOHN W ,  BARA THOMAS A ,  XU RUO ,  LI HONGMEI ,  PISSARNITSKI DMITRI ,  ZHAO ZHIQIANG

IPC: A61K20100101 ,  A61P20100101 ,  C07D20100101

Abstract: Disclosed are novel gamma secretase inhibitors of the formula: Also disclosed are methods for inhibiting gamma secretase, for treating one or more neurodegenerative diseases, for inhibiting the deposition of beta amyloid protein, and for treating Alzheimer's disease using the compounds of formula (I).

公开(公告)号：CA2526725A1

公开(公告)日：2005-01-20

申请号：CA2526725

申请日：2004-06-28

Applicant: SCHERING CORP

Inventor： PUSHPAVANAM PRADEEP B ,  CLADER JOHN W ,  BARA THOMAS A ,  PALANI ANANDAN ,  SHAPIRO SHERRY A ,  JOSIEN HUBERT B ,  MCBRIAR MARK ,  LI SHENGJIAN

IPC: C07D409/14 ,  A61K31/496 ,  C07D409/06

Abstract: The present invention discloses methods of using antagonists for melanin- concentrating hormone (MCH), to treat obesity, metabolic disorders, eating disorders such as hyperphagia, and diabetes, as well as novel compounds whic h are antagonists for melanin-concentrating hormone (MCH). In other aspects, t he invention is directed to pharmaceutical compositions comprising such MCH antagonists as well as methods for preparing such compounds. Compounds of th e invention generally have the structure of formula (I) where the substituents are as defined herein.

公开(公告)号：AT461926T

公开(公告)日：2010-04-15

申请号：AT05790194

申请日：2005-06-28

Applicant: SCHERING CORP

Inventor： JOSIEN HUBERT B ,  CLADER JOHN W ,  BARA THOMAS A ,  XU RUO ,  LI HONGMEI ,  PISSARNITSKI DMITRI ,  ZHAO ZHIQIANG

IPC: C07D265/30 ,  A61K31/5377 ,  A61P25/28 ,  C07D413/12 ,  C07D451/02 ,  C07D487/08

Abstract: Disclosed are novel gamma secretase inhibitors of the formula: Also disclosed are methods for inhibiting gamma secretase, for treating one or more neurodegenerative diseases, for inhibiting the deposition of beta amyloid protein, and for treating Alzheimer's disease using the compounds of formula (I).

公开(公告)号：AU2008275735A2

公开(公告)日：2010-02-11

申请号：AU2008275735

申请日：2008-07-01

Applicant: SCHERING CORP

Inventor： PISSARNITSKI DMITRI A ,  JOSIEN HUBERT B ,  WU WEN-LIAN ,  LI HONGMEI ,  BARA THOMAS A ,  CLADER JOHN W ,  SASIKUMAR THAVALAKULAMGARA K ,  WONG JESSE K ,  MCNAMARA PAUL ,  ZHAO ZHIQIANG ,  BURNETT DUANE A ,  LIANG XIAN ,  XU RUO ,  DOMALSKI MARTIN S ,  JIN YAN

IPC: A61K31/35 ,  A61K31/352 ,  A61P25/28 ,  C07D311/78 ,  C07D407/12 ,  C07D493/04

Abstract: Disclosed are novel gamma secretase inhibitors of the formula. Also disclosed are methods of inhibiting gamma-secretase, methods of treating neurodegenerative diseases, and methods of treating Alzheimer's Disease. Also disclosed are processes for preparing alkenes in one reaction step using a mixture of an aldehyde (or ketone) and an alkyl substituted with two electron withdrawing groups, and reacting the mixture with: (a) a sulfonyl halide (e.g., a sulfonyl chloride) and a basic tertiary amine, or, (b) a sulfonyl anhydride and a basic amine, or (c) an aryl-C(O)-halide and a basic tertiary amine, or (d) an aryl-C(O)-O-C(O)-aryl and a basic tertiary amine, or (e) an heteroaryl-C(O)-halide and a basic tertiary amine, or (f) a heteroaryl-C(O)-O-C(O)-heteroaryl and a basic tertiary amine.

公开(公告)号：AU2008275735A1

公开(公告)日：2009-01-15

申请号：AU2008275735

申请日：2008-07-01

Applicant: SCHERING CORP

Inventor： PISSARNITSKI DMITRI A ,  JOSIEN HUBERT B ,  WU WEN-LIAN ,  LI HONGMEI ,  BARA THOMAS A ,  CLADER JOHN W ,  SASIKUMAR THAVALAKULAMGARA K ,  WONG JESSE K ,  MCNAMARA PAUL ,  ZHAO ZHIQIANG ,  BURNETT DUANE A ,  LIANG XIAN ,  XU RUO ,  DOMALSKI MARTIN S ,  JIN YAN

IPC: A61K31/35 ,  A61K31/352 ,  A61P25/28 ,  C07D311/78 ,  C07D407/12 ,  C07D493/04

Abstract: Disclosed are novel gamma secretase inhibitors of the formula. Also disclosed are methods of inhibiting gamma-secretase, methods of treating neurodegenerative diseases, and methods of treating Alzheimer's Disease. Also disclosed are processes for preparing alkenes in one reaction step using a mixture of an aldehyde (or ketone) and an alkyl substituted with two electron withdrawing groups, and reacting the mixture with: (a) a sulfonyl halide (e.g., a sulfonyl chloride) and a basic tertiary amine, or, (b) a sulfonyl anhydride and a basic amine, or (c) an aryl-C(O)-halide and a basic tertiary amine, or (d) an aryl-C(O)-O-C(O)-aryl and a basic tertiary amine, or (e) an heteroaryl-C(O)-halide and a basic tertiary amine, or (f) a heteroaryl-C(O)-O-C(O)-heteroaryl and a basic tertiary amine.

公开(公告)号：PE13212007A1

公开(公告)日：2007-12-29

申请号：PE0000552007

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

CPC classification number: C07D311/22 ,  C07C317/14 ,  C07C317/20 ,  C07C317/44 ,  C07C2602/08 ,  C07C2602/10 ,  C07C2602/12 ,  C07D311/80 ,  C07D311/92 ,  C07D311/94 ,  C07D313/08 ,  C07D335/06 ,  C07D405/12 ,  C07D409/12 ,  C07D491/04 ,  C07D493/04

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：DE602005020156D1

公开(公告)日：2010-05-06

申请号：DE602005020156

申请日：2005-06-28

Applicant: SCHERING CORP

Inventor： JOSIEN HUBERT B ,  CLADER JOHN W ,  BARA THOMAS A ,  XU RUO ,  LI HONGMEI ,  PISSARNITSKI DMITRI ,  ZHAO ZHIQIANG

IPC: C07D265/30 ,  A61K31/5377 ,  A61P25/28 ,  C07D413/12 ,  C07D451/02 ,  C07D487/08

Abstract: Disclosed are novel gamma secretase inhibitors of the formula: Also disclosed are methods for inhibiting gamma secretase, for treating one or more neurodegenerative diseases, for inhibiting the deposition of beta amyloid protein, and for treating Alzheimer's disease using the compounds of formula (I).

公开(公告)号：PE20090435A1

公开(公告)日：2009-04-18

申请号：PE2008001121

申请日：2008-07-02

Applicant: SCHERING CORP

Inventor： BARA THOMAS A ,  BURNETT DUANE A ,  CLADER JOHN W ,  DOMALSKI MARTIN S ,  JIN YAN ,  JOSIEN HUBERT B ,  LI HONGMEI ,  LIANG XIAN ,  PISSARNITSKI DMITRI ,  SASIKUMAR TRAVALAKULAMGARA K ,  WONG JESSE K ,  XU RUO ,  ZHAO ZHIQIANG ,  MCNAMARA PAUL E ,  WU WEN-LIAN

IPC: A61K31/35 ,  A61K31/352 ,  A61P25/28 ,  C07D311/78 ,  C07D407/12 ,  C07D493/04

Abstract: REFERIDA A UN COMPUESTO DE FORMULA (I), DONDE X ES N, CH2; R1 ES -ALQUILEN-SO2-ALQUILO(C1-C6), -ALQUILEN-SO2-HALOALQUILO(C1-C6), ALQUILEN-(1,1-DIOXIDO DE TETRAHIDROTIOFENO), ENTRE OTROS; R2 ES H, ALQUILO; Ar ES ARILO, HETEROARILO, ARILO SUSTITUIDO CON UNO O MAS L1A, ENTRE OTROS; L1A ES HALOGENO, ALQUILO, -CN, CF3, -O-(HALOALQUILO(C1-C6)), ENTRE OTROS; L1 ES HALOGENO, -CN, -CF3, -O-ALQUILO(C1-C6), -C(O)-O-ALQUILO(C1-C6), ALQUILEN-OH, ENTRE OTROS; n ES 0-3. SON COMPUESTOS PREFERIDOS: (a), (b), ENTRES OTROS. SE REFIERE TAMBIEN UN PROCEDIMIENTO DE PREPARACION Y A UNA COMPOSICION FARMACEUTICA. DICHOS COMPUESTOS SON INHIBIDRORES DE GAMMA-SECRETASA, UTILES EN EL TRATAMIENTO DE ENFERMEDADES NEURODEGENERATIVAS, ENFERMEDAD DE ALZHEIMER E INHIBIENDO EL DEPOSITO DE PROTEINA AMIELOIDE EN, SOBRE O ALREDEDOR DEL TEJIDO NEUROLOGICO