公开(公告)号：DE69706813T2

公开(公告)日：2002-04-04

申请号：DE69706813

申请日：1997-12-01

Applicant: HOFFMANN LA ROCHE

Inventor： ALANINE ALEXANDER ,  BUETTELMANN BERND ,  HEITZ NEIDHART MARIE-PAULE ,  PINARD EMMANUEL ,  WYLER RENE

IPC: C07D211/44 ,  A61K31/38 ,  A61K31/4427 ,  A61K31/443 ,  A61K31/445 ,  A61K31/451 ,  A61K31/453 ,  A61K31/454 ,  A61K31/47 ,  A61P25/00 ,  A61P25/14 ,  A61P25/16 ,  A61P25/28 ,  A61P43/00 ,  C07D211/14 ,  C07D211/48 ,  C07D215/12 ,  C07D215/18 ,  C07D307/78 ,  C07D335/06 ,  C07D401/06 ,  C07D405/06 ,  C07D417/06 ,  A61K31/34 ,  A61K31/35

Abstract: The present invention relates to 4-hydroxy-piperidine derivatives of the general formulawhereinX denotes -O-, -NH-, -CH2-, -CH=, -CHOH-, -CO-, -S-, -SO- or -SO2-;R1-R4 are, independently from each other, hydrogen, hydroxy, lower-alkyl-sulfonylamino, 1- or 2-imidazolyl or acetamido;R5-R8 are, independently from each other, hydrogen, hydroxy, lower-alkyl, halogen, lower-alkoxy, trifluoromethyl or trifluoromethyloxy;a and b may be a double bond, provided that when "a" is a double bond, "b" cannot be a double bond;n is 0-2;m is 1-3;p is 0 or 1and to pharmaceutically acceptable addition salts thereof.Compounds of the present invention are NMDA(N-methyl-D-aspartate)-receptor subtype selective blockers, which can be used in mediating processes underlying development of CNS including learning and memory formation and function.

公开(公告)号：HRP20000652A2

公开(公告)日：2001-12-31

申请号：HRP20000652

申请日：2000-10-03

Applicant: HOFFMANN LA ROCHE

Inventor： ALANINE ALEXANDER ,  BURNER SERGE ,  BUETTELMANN BERND ,  NEIDHART MARIE-PAULE HEITZ ,  JAESCHKE GEORG ,  PINARD EMMANUEL ,  WYLER RENE

IPC: C07D215/42 ,  A61K31/4709 ,  A61K31/4725 ,  A61P21/00 ,  A61P25/00 ,  A61P25/04 ,  A61P25/14 ,  A61P25/16 ,  A61P25/28 ,  A61P29/00 ,  A61P43/00 ,  C07D401/04 ,  C07D401/14 ,  A61K31/47

Abstract: The present invention relates to compounds of the general formula wherein R is hydrogen, lower alkyl, lower alkoxy, hydroxy, amino, nitro, cyano, lower alkyl-amino, di-lower alkyl-amino or halogen; R is hydrogen, lower alkyl, amino, pyrrolidin-3-ol, pyrrolidin-2-yl-methanol or -NHCH2CHROH; R is hydrogen or halogen; R is hydrogen, lower alkyl or -CH2OH; n is 1 or 2; and to pharmaceutically acceptable acid addition salts thereof. Compounds of the present invention are NMDA(N-methyl-D-aspartate)-receptor subtype selective blockers, which have a key function in modulating neuronal activity and plasticity in mediating processes underlying development of CNS as well as learning and memory formation.

公开(公告)号：DE69707782D1

公开(公告)日：2001-12-06

申请号：DE69707782

申请日：1997-07-10

Applicant: HOFFMANN LA ROCHE

Inventor： ALANINE ALEXANDER ,  BUETTELMANN BERND ,  HEITZ NEIDHART MARIE-PAULE ,  PINARD EMMANUEL ,  WYLER RENE ,  ROEVER STEPHAN

IPC: C07D211/14 ,  A61K31/445 ,  A61K31/452 ,  A61K31/4523 ,  A61P25/00 ,  A61P25/16 ,  A61P25/28 ,  A61P43/00 ,  C07D20060101 ,  C07D211/18 ,  C07D211/20 ,  C07D211/48 ,  C07D401/06 ,  C07D401/08 ,  C07D401/12 ,  C07D521/00

Abstract: The present invention relates to compounds of the general formula wherein X is -O-, -NH-, -CH2-, -CH=, -CO2-, -CONH-, -CON(lower alkyl)-, -S- and -SO2-; R - R are, independently from each other hydrogen, halogen, hydroxy, amino, nitro, lower-alkyl-sulfonylamido, 1- or 2-imidazolyl, 1-(1,2,4-triazolyl) or acetamido; R , R are, independently from each other hydrogen, lower-alkyl, hydroxy, lower alkoxy or oxo; R -R are, independently from each other hydrogen, lower-alkyl, halogen, trifluoromethyl or lower-alkoxy; n is 0 or 1; and to pharmaceutically acceptable acid addition salts thereof. Compounds of the present invention are NMDA(N-methyl-D-aspartate)-receptor subtype selective blockers.

公开(公告)号：NO20015920L

公开(公告)日：2001-12-04

申请号：NO20015920

申请日：2001-12-04

Applicant: HOFFMANN LA ROCHE

Inventor： ALANINE ALEXANDER ,  BURNER SERGE ,  BUETTELMANN BERND ,  HEITZ MARIE-PAULE NEIDHART ,  JAESCHKE GEORG ,  PINARD EMMANUEL ,  WYLER RENE

IPC: A61K31/445 ,  A61P21/00 ,  A61P25/00 ,  A61P25/04 ,  A61P25/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  C07D211/14 ,  C07D211/30 ,  C07D211/42 ,  C07D211/44 ,  C07D211/46

Abstract: The invention relates to compounds of the general formulawhereinR1 signifies hydrogen or hydroxy; R2 signifies hydrogen or methyl; and X signifies -O- or -CH2- and their pharmaceutically acceptable acid addition salts.It has been shown that these compounds have a good affitity to the NMDA receptor and they are therefore useful in the treatment of diseases, wherein the therapeutic indications include acute forms of neurodegeneration caused, e.g., by stroke or brain trauma; chronic forms of neurodegeneration such as Alzheimer's disease, Parkinson's disease, Huntington's disease or ALS (amyotrophic lateral sclerosis); neurodegeneration associated with bacterial or viral infections, and, diseases such as schizophrenia, anxiety, depression and chronic/acute pain.

公开(公告)号：NO20015920D0

公开(公告)日：2001-12-04

申请号：NO20015920

申请日：2001-12-04

Applicant: HOFFMANN LA ROCHE

Inventor： ALANINE ALEXANDER ,  BURNER SERGE ,  BUETTELMANN BERND ,  HEITZ MARIE-PAULE NEIDHART ,  JAESCHKE GEORG ,  PINARD EMMANUEL ,  WYLER RENE

IPC: A61K31/445 ,  A61P21/00 ,  A61P25/00 ,  A61P25/04 ,  A61P25/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  C07D211/14 ,  C07D211/30 ,  C07D211/42 ,  C07D211/44 ,  C07D211/46 ,  C07D

Abstract: The invention relates to compounds of the general formulawhereinR1 signifies hydrogen or hydroxy; R2 signifies hydrogen or methyl; and X signifies -O- or -CH2- and their pharmaceutically acceptable acid addition salts.It has been shown that these compounds have a good affitity to the NMDA receptor and they are therefore useful in the treatment of diseases, wherein the therapeutic indications include acute forms of neurodegeneration caused, e.g., by stroke or brain trauma; chronic forms of neurodegeneration such as Alzheimer's disease, Parkinson's disease, Huntington's disease or ALS (amyotrophic lateral sclerosis); neurodegeneration associated with bacterial or viral infections, and, diseases such as schizophrenia, anxiety, depression and chronic/acute pain.

公开(公告)号：AU7394201A

公开(公告)日：2001-11-07

申请号：AU7394201

申请日：2001-04-11

Applicant: HOFFMANN LA ROCHE

Inventor： ALANINE ALEXANDER ,  BUETTELMANN BERND ,  NEIDHART MARIE-PAULE HEITZ ,  JAESCHKE GEORG ,  PINARD EMMANUEL ,  WYLER RENE

IPC: A61K31/395 ,  A61K31/397 ,  A61K31/40 ,  A61K31/401 ,  A61K31/4035 ,  A61K31/404 ,  A61K31/416 ,  A61K31/423 ,  A61K31/427 ,  A61K31/44 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/445 ,  A61K31/454 ,  A61P21/04 ,  A61P25/14 ,  A61P25/16 ,  A61P25/28 ,  A61P43/00 ,  C07D205/04 ,  C07D207/12 ,  C07D209/34 ,  C07D211/54 ,  C07D231/56 ,  C07D263/58 ,  C07D401/04 ,  C07D401/06 ,  C07D403/06 ,  C07D403/12 ,  C07D413/12

Abstract: The invention relates to treating neurodegeneration by selective blocking of NMDA receptor with compounds of formulawhereinAr1 is pyridyl or phenyl, substituted by hydroxy, lower alkyl, halogen, amino, nitro, benzyloxy or lower alkoxy-lower alkoxy, or is the group whereinZ1 is a five membered heterocyclic ring, which contains one or two heteroatoms, selected from N or O;R1 is hydrogen, hydroxy or an oxo group;Ar2 is pyridyl or phenyl, optionally substituted by hydroxy, lower alkyl, halogen, amino, nitro, benzyloxy or lower alkoxy-lower alkoxy, or is the group whereinZ2 is a five or six membered ring, which optionally contains one or two heteroatoms, selected from N or O; andQ, X, A, Y B are as defined in the specification.

公开(公告)号：CA2407345A1

公开(公告)日：2001-11-01

申请号：CA2407345

申请日：2001-04-17

Applicant: HOFFMANN LA ROCHE

Inventor： JAESCHKE GEORG ,  PINARD EMMANUEL ,  BUETTELMANN BERND ,  HEITZ NEIDHART MARIE-PAULE ,  ALANINE ALEXANDER ,  WYLER RENE

IPC: C07D211/50 ,  A61K31/445 ,  A61P21/04 ,  A61P25/06 ,  A61P25/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P29/00 ,  C07D211/48 ,  A61K31/44

Abstract: The invention relates to a compound of formula (I), its R,R- and S,S- enantiomeres and to their pharmaceutically acceptable acid addition salts. T he compound of formula (I) and its R,R- and S,S-enantiomeres may be used as medicaments for the treatment of diseases, wherein the therapeutic indicatio ns include acute forms of neurodegeneration caused by stroke or brain trauma; chronic forms of neurodegeneration such as Alzheimer's disease, Parkinson's disease, Huntington's disease or ALS (amyotrophic lateral sclerosis); neurodegeneration associated with bacterial or viral infections, and disease s such as schizophrenia, anxiety, depression and chronic/acute pain.

公开(公告)号：AT205830T

公开(公告)日：2001-10-15

申请号：AT97121040

申请日：1997-12-01

Applicant: HOFFMANN LA ROCHE

Inventor： ALANINE ALEXANDER ,  BUETTELMANN BERND ,  HEITZ NEIDHART MARIE-PAULE ,  PINARD EMMANUEL ,  WYLER RENE

IPC: C07D211/44 ,  A61K31/38 ,  A61K31/4427 ,  A61K31/443 ,  A61K31/445 ,  A61K31/451 ,  A61K31/453 ,  A61K31/454 ,  A61K31/47 ,  A61P25/00 ,  A61P25/14 ,  A61P25/16 ,  A61P25/28 ,  A61P43/00 ,  C07D211/14 ,  C07D211/48 ,  C07D215/12 ,  C07D215/18 ,  C07D307/78 ,  C07D335/06 ,  C07D401/06 ,  C07D405/06 ,  C07D417/06 ,  A61K31/34 ,  A61K31/35

Abstract: The present invention relates to 4-hydroxy-piperidine derivatives of the general formulawhereinX denotes -O-, -NH-, -CH2-, -CH=, -CHOH-, -CO-, -S-, -SO- or -SO2-;R1-R4 are, independently from each other, hydrogen, hydroxy, lower-alkyl-sulfonylamino, 1- or 2-imidazolyl or acetamido;R5-R8 are, independently from each other, hydrogen, hydroxy, lower-alkyl, halogen, lower-alkoxy, trifluoromethyl or trifluoromethyloxy;a and b may be a double bond, provided that when "a" is a double bond, "b" cannot be a double bond;n is 0-2;m is 1-3;p is 0 or 1and to pharmaceutically acceptable addition salts thereof.Compounds of the present invention are NMDA(N-methyl-D-aspartate)-receptor subtype selective blockers, which can be used in mediating processes underlying development of CNS including learning and memory formation and function.

公开(公告)号：PE20010759A1

公开(公告)日：2001-07-19

申请号：PE0010962000

申请日：2000-10-12

Applicant: HOFFMANN LA ROCHE

Inventor： ALANINE ALEXANDER ,  MUTEL VINCENT ,  ADAM GEO ,  WOLTERING THOMAS JOHANNES ,  GOETSCHI ERWIN

IPC: A61K31/55 ,  A61K31/551 ,  A61K31/5513 ,  A61P1/08 ,  A61P3/08 ,  A61P9/08 ,  A61P13/02 ,  A61P21/02 ,  A61P21/04 ,  A61P25/00 ,  A61P25/06 ,  A61P25/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/34 ,  A61P25/36 ,  A61P27/02 ,  A61P29/02 ,  A61P43/00 ,  C07D243/00 ,  C07D243/12 ,  C07D401/04 ,  C07D401/06 ,  C07D401/14 ,  C07D403/10 ,  C07D405/04 ,  C07D405/06 ,  C07D409/04 ,  C07D409/08 ,  C07D409/14 ,  C07D413/10 ,  C07D417/02 ,  C07D417/04 ,  C07D417/06 ,  C07D417/10 ,  C07D417/14

Abstract: SE REFIERE A BENZO[b][1,4]DIAZEPIN-2-ONA DE FORMULA I, CUANDO X ES UN ENLACE, R1 ES H, HALOGENO, NITRO, ALQUILO, HALOALQUILO, ALCOXICARBONILO, ENTRE OTROS; CUANDO X ES UN ETINODIILO; R1 ES H, ALQUILO OPCIONALMENTE SUSTITUIDO CON OH, ALQUILO, HALOALQUILO, ENTRE OTROS; R3 ES FENILO, PIRIDINA, TIOFENILO, TIAZOLILO OPCIONALMENTE SUSTITUIDO CON HALOGENO, CIANO, NITRO, AZIDO, ENTRE OTROS; SI X ES UN ENLACE; R3 ES PIRIDINILO; R1 NO ES H, METILO. SON COMPUESTOS PREFERIDOS 3-(4-OXO-7-FENILETINIL-4,5-DIHIDRO-3H-BENZO[b][1,4]DIAZEPIN-2-IL)BENZONITRILO, 4-(3-CLORO-FENIL)-8-FENILETINIL-1,3-DIHIDRO-BENZO[b][1,4]DIAZEPIN-2-ONA, 4-(3-IMIDAZOL-1-IL-FENIL)-8-FENILETINIL-1,3-DIHIDRO-BENZO[b][1,4]-DIAZEPIN-2-ONA, 8-(4--FLUORO-FENILETINIL)-4-(2-IMIDAZOL-1-IL-PIRIDIN-4-IL)-1,3-DIHIDRO-BENZO[b][1,4]DIAZEPIN-2-ONA, ENTRE OTROS. TAMBIEN SE REFIERE A UN PROCEDMIENTO PARA LA PREPARACION. EL COMPUESTO I ES UN INHIBIDOR DEL RECEPTOR DE GLUTAMATO METABOTROPICO Y PUEDE SER UTIL PARA EL TRATAMIETNO DE PSICOSIIS, ESQUIZOFRENIA, ALZHEIMER, TRASTORNOS COGNITIVOS, DEFICITS DE LA MEMORIA

公开(公告)号：PE07592001A1

公开(公告)日：2001-07-19

申请号：PE0010962000

申请日：2000-10-12

Applicant: HOFFMANN LA ROCHE

Inventor： ALANINE ALEXANDER ,  MUTEL VINCENT ,  ADAM GEO ,  WOLTERING THOMAS JOHANNES ,  GOETSCHI ERWIN

IPC: A61K31/55 ,  A61K31/551 ,  A61K31/5513 ,  A61P1/08 ,  A61P3/08 ,  A61P9/08 ,  A61P13/02 ,  A61P21/02 ,  A61P21/04 ,  A61P25/00 ,  A61P25/06 ,  A61P25/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/34 ,  A61P25/36 ,  A61P27/02 ,  A61P29/02 ,  A61P43/00 ,  C07D243/00 ,  C07D243/12 ,  C07D401/04 ,  C07D401/06 ,  C07D401/14 ,  C07D403/10 ,  C07D405/04 ,  C07D405/06 ,  C07D409/04 ,  C07D409/08 ,  C07D409/14 ,  C07D413/10 ,  C07D417/02 ,  C07D417/04 ,  C07D417/06 ,  C07D417/10 ,  C07D417/14

CPC classification number: C07D401/04 ,  C07D243/12 ,  C07D403/10 ,  C07D405/06 ,  C07D413/10 ,  C07D417/06 ,  C07D417/10

Abstract: SE REFIERE A BENZO[b][1,4]DIAZEPIN-2-ONA DE FORMULA I, CUANDO X ES UN ENLACE, R1 ES H, HALOGENO, NITRO, ALQUILO, HALOALQUILO, ALCOXICARBONILO, ENTRE OTROS; CUANDO X ES UN ETINODIILO; R1 ES H, ALQUILO OPCIONALMENTE SUSTITUIDO CON OH, ALQUILO, HALOALQUILO, ENTRE OTROS; R3 ES FENILO, PIRIDINA, TIOFENILO, TIAZOLILO OPCIONALMENTE SUSTITUIDO CON HALOGENO, CIANO, NITRO, AZIDO, ENTRE OTROS; SI X ES UN ENLACE; R3 ES PIRIDINILO; R1 NO ES H, METILO. SON COMPUESTOS PREFERIDOS 3-(4-OXO-7-FENILETINIL-4,5-DIHIDRO-3H-BENZO[b][1,4]DIAZEPIN-2-IL)BENZONITRILO, 4-(3-CLORO-FENIL)-8-FENILETINIL-1,3-DIHIDRO-BENZO[b][1,4]DIAZEPIN-2-ONA, 4-(3-IMIDAZOL-1-IL-FENIL)-8-FENILETINIL-1,3-DIHIDRO-BENZO[b][1,4]-DIAZEPIN-2-ONA, 8-(4--FLUORO-FENILETINIL)-4-(2-IMIDAZOL-1-IL-PIRIDIN-4-IL)-1,3-DIHIDRO-BENZO[b][1,4]DIAZEPIN-2-ONA, ENTRE OTROS. TAMBIEN SE REFIERE A UN PROCEDMIENTO PARA LA PREPARACION. EL COMPUESTO I ES UN INHIBIDOR DEL RECEPTOR DE GLUTAMATO METABOTROPICO Y PUEDE SER UTIL PARA EL TRATAMIETNO DE PSICOSIIS, ESQUIZOFRENIA, ALZHEIMER, TRASTORNOS COGNITIVOS, DEFICITS DE LA MEMORIA