公开(公告)号：JP2004339204A

公开(公告)日：2004-12-02

申请号：JP2004118943

申请日：2004-04-14

Applicant: F Hoffmann La Roche Ag ,  エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft

Inventor： CESURA ANDREA ,  PINARD EMMANUEL

IPC: C12Q1/02 ,  A61K31/12 ,  A61K31/122 ,  A61K31/277 ,  A61K31/35 ,  A61K31/353 ,  A61P25/28 ,  A61P43/00 ,  C07C49/665 ,  C07C49/683 ,  C07C255/47 ,  C07D311/22 ,  C07D311/56

CPC classification number: C07C255/47 ,  A61K31/12 ,  A61K31/35 ,  C07C49/665 ,  C07C49/683 ,  C07C2601/10 ,  C07C2603/32 ,  C07C2603/98 ,  C07D311/22

Abstract: PROBLEM TO BE SOLVED: To provide a method for examining and modulating mitochondria permeability and apoptosis, and to obtain a reagent.
SOLUTION: A compound selected from the group consisting of a compound of formula I and a compound of formula II is used as a modulator and an affinity label of an MPTP complex. Further, the method for modulating the activity of the MPTP complex, a method for determining the presence of the components of the MPTP complex, and a method for identifying an active agent for modulating the activity of the MPTP complex are provided. Concretely, the method for identifying the active agent for modulating the activity of the MPTP complex by interacting with a VDAC1 component is also provided.
COPYRIGHT: (C)2005,JPO&NCIPI

公开(公告)号：JP2000026466A

公开(公告)日：2000-01-25

申请号：JP16194399

申请日：1999-06-09

Applicant: HOFFMANN LA ROCHE

Inventor： ADAM GEO ,  CESURA ANDREA ,  JENCK FRANCOIS ,  KOLCZEWSKI SABINE ,  ROEVER STEPHAN ,  WICHMANN JUERGEN

IPC: C07D401/04 ,  A61K20060101 ,  A61K31/00 ,  A61K31/395 ,  A61K31/40 ,  A61K31/435 ,  A61K31/438 ,  A61K31/44 ,  A61K31/445 ,  A61P3/04 ,  A61P3/12 ,  A61P9/00 ,  A61P25/00 ,  A61P25/02 ,  A61P25/04 ,  A61P25/08 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/30 ,  A61P25/36 ,  A61P43/00 ,  C07D20060101 ,  C07D207/00 ,  C07D209/00 ,  C07D211/00 ,  C07D221/00 ,  C07D271/00 ,  C07D277/00 ,  C07D401/00 ,  C07D401/14 ,  C07D405/04 ,  C07D409/04 ,  C07D413/04 ,  C07D417/04 ,  C07D471/10 ,  C07D471/20 ,  C07D487/12 ,  C07D498/10 ,  C07D513/10

Abstract: PROBLEM TO BE SOLVED: To obtain a novel compound that is an agonist and antagonist of Orphanin FQ(OFQ) receptor and is useful for treatment of psychological disorder, neurological disorder and physiological disorder. SOLUTION: This is a new compound represented by formula I [R1 is a (substituted) 6-10C cycloalkyl, decahydro-naphthalen-1-yl, indan-1-yl, or the like; R2 is H, a lower alkyl, =O, or a (substituted) phenyl; group A is a (substituted) cyclohexyl or phenyl; X is -CH(OH)-, -C(O)- or the like; Y is -CH2-, -CH=, -N= or the like; a and b mean actual additive bonds], typically (RS)-8-(cis-4- isopropyl-cyclohexyl)-1-phenyl-1,8-diaza-spiro[4.5]decan-4-ol. The compound of formula I is prepared by reductive amination of a compound of formula II with a compound of formula II.

公开(公告)号：JPH1067761A

公开(公告)日：1998-03-10

申请号：JP19099097

申请日：1997-07-16

Applicant: HOFFMANN LA ROCHE

Inventor： CESURA ANDREA ,  ROVER STEPHAN

IPC: C07D277/20 ,  A61K31/00 ,  A61K31/425 ,  A61K31/426 ,  A61K31/427 ,  A61K31/44 ,  A61K31/4427 ,  A61K31/4439 ,  A61P9/00 ,  A61P25/00 ,  A61P25/08 ,  A61P25/18 ,  A61P25/20 ,  A61P25/28 ,  A61P31/00 ,  A61P37/00 ,  A61P37/02 ,  A61P43/00 ,  C07D277/00 ,  C07D277/02 ,  C07D277/22 ,  C07D277/50 ,  C07D277/52 ,  C07D417/12

Abstract: PROBLEM TO BE SOLVED: To obtain the subject new compound, having high activities as a kynurenine-3-hydroxylase inhibitor and useful for treating or preventing sequelae, etc., to neurodegenerative disorder, cerebral apoplexy and/or cerebral ischemia. SOLUTION: This compound is represented by formula I (R is a lower alkyl, phenyl, benzyl, etc., preferably 4-methylphenyl, 4-methoxyphenyl, 2-naphthyl, etc.; R to R are each H, a halogen, hydroxy, a lower alkyl, etc., preferably H, F, nitro, etc.) or its pharmaceutically permissible salt, e.g. 4-methoxy-N-(4- naphthalen-2-yl-thiazole-2-yl)-benzenesulfonamide. For example, a method for reacting a compound represented by formula II with a sulfonyl halide represented by the formula R-SO2 X (X is a halogen) is cited in order to obtain the compound represented by formula I. Thereby, the compound is effective in treating or preventing neuropathy or psychiatric diseases caused by neurodegenerative diseases or activation of an immune system.

公开(公告)号：JP2000053679A

公开(公告)日：2000-02-22

申请号：JP16357099

申请日：1999-06-10

Applicant: HOFFMANN LA ROCHE

Inventor： WICHMANN JUERGEN ,  ROEVER STEPHAN ,  ADAM GEO ,  CESURA ANDREA ,  KOLCZEWSKI SABINE ,  JENCK FRANCOIS

IPC: C07D401/00 ,  A61K31/00 ,  A61K31/438 ,  A61P3/04 ,  A61P9/10 ,  A61P25/04 ,  A61P25/08 ,  A61P25/18 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/30 ,  C07D471/10 ,  A61K31/435

Abstract: PROBLEM TO BE SOLVED: To obtain a new diaza-spiro[3,5]-nonane derivative useful for treating psychiatric, neurological and physiological disorders, e.g. diseases related to orphanin FQ receptor including anxiety, stress disorder, Alzheimer's disease and depression by dementia, etc. SOLUTION: This compound is shown by formula I (R1 is a 6-12C cycloalkyl substitutable with a lower alkyl or the like; R2 is O or the like; R3 is H, isoindolyl-1,3-dione or the like; R4 is H or the like; a group of formula II is a cyclohexyl substitutable with a lower alkyl or the like) preferably 3,3-bis- hydroxymethyl-7-(cis-4-isopropyl-cyclohexyl)-1-phenyl-1,7-diaza-spiro[ 3,5]nonan-2- one or the like. The compound of formula I is obtained by a process for reductively reducing a compound of formula III (e.g. 4-isopropyl-cyclohexanone or the like) with a compound of formula IV e.g. 3,3-bis-hydroxymethyl-1- phenyl-1,7-diaza-spiro[3,5]nonan-2-one or the like}, etc.

公开(公告)号：JPH11228575A

公开(公告)日：1999-08-24

申请号：JP34527898

申请日：1998-12-04

Applicant: HOFFMANN LA ROCHE

Inventor： ADAM GEO ,  CESURA ANDREA ,  GALLEY GUIDO ,  JENCK FRANCOIS ,  ROEVER STEPHAN ,  WICHMANN JUERGEN

IPC: C07D235/02 ,  A61K31/00 ,  A61K31/41 ,  A61K31/435 ,  A61K31/438 ,  A61P3/00 ,  A61P3/04 ,  A61P9/00 ,  A61P25/00 ,  A61P25/02 ,  A61P25/04 ,  A61P25/08 ,  A61P25/18 ,  A61P25/20 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/30 ,  A61P43/00 ,  C07D207/04 ,  C07D233/30 ,  C07D471/10

Abstract: PROBLEM TO BE SOLVED: To obtain a new compound useful for treating diseases associated with an Orphanin FQ(OFQ) receptor such as anxiety disorder and stress disorder, depression, trauma and amnesia due to Alzheimer disease or other dementias. SOLUTION: This compound is represented by formula I (R is H or the like; R is H or the like; R is H or the like; R is H or the like; A is a ring system or the like such as a 5-15C cycloalkyl which may be substituted with a lower alkyl or the like in addition to R ), preferably 8-(decahydro-naphthalen-2- yl)-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-one or the like. The compound represented by formula I is obtained by reductively aminating a compound represented by formula II [e.g. octahydro-2-(1H)-naphthalenone] with a compound represented by formula III e.g. 1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one} in the presence of a reducing agent such as sodium borohydride in a solvent such as toluene.

公开(公告)号：JPH10212290A

公开(公告)日：1998-08-11

申请号：JP1371198

申请日：1998-01-27

Applicant: HOFFMANN LA ROCHE

Inventor： ADAM GEO ,  CESURA ANDREA ,  GALLEY GUIDO ,  JENCK FRANCOIS ,  MONSMA FREDERICK ,  ROEVER STEPHAN ,  WICHMANN JUERGEN

IPC: C07D233/04 ,  A61K31/00 ,  A61K31/41 ,  A61K31/435 ,  A61K31/438 ,  A61K31/445 ,  A61K31/55 ,  A61K51/02 ,  A61P3/04 ,  A61P3/12 ,  A61P9/00 ,  A61P9/12 ,  A61P25/00 ,  A61P25/04 ,  A61P25/08 ,  A61P25/18 ,  A61P25/20 ,  A61P25/24 ,  A61P25/26 ,  A61P25/28 ,  A61P25/30 ,  A61P43/00 ,  C07D215/58 ,  C07D305/14 ,  C07D471/00 ,  C07D471/10 ,  C07D498/00

Abstract: PROBLEM TO BE SOLVED: To obtain the subject new compound which is an agonist for OFQ receptor and/or an antagonist useful for treating mental disturbance, nervous disturbance and physiological disorder. SOLUTION: This compound is shown by formula I (R and R are each H, a lower alkyl, etc.; R is phenyl; R is H, a lower alkyl, an acyl, etc.; R and R are each H, a lower alkyl, etc., or bonded together to form a phenyl ring; R and one of R and R can be bonded to form a 6-memered ring; A is a saturated 4- to 7-membered ring containing a hetero atom such as O or S) or its acid addition salt such as 8-(8-chloro-1,2,3,4,-tetrahydro-naphthyl-2)-1- phenyl-1,3,8-triaza-spiro[4,5]decan-4-one. The compound of formula I is obtained by hydrogenating a double bond in a compound of formula II (A' is a 5 to 7-membered ring containing a hetero atom such as O or S). The compound is useful for treating anxiety, stress disorder, depression, traumatic disorder, amnesia caused by Alzheimer's disease or other dementia, epilepsy and convulsion.

公开(公告)号：CA2483461C

公开(公告)日：2010-12-21

申请号：CA2483461

申请日：2003-04-14

Applicant: HOFFMANN LA ROCHE

Inventor： CESURA ANDREA ,  RODRIGUEZ SARMIENTO ROSA MARIA ,  SCALONE MICHELANGELO ,  THOMAS ANDREW WILLIAM ,  WYLER RENE

IPC: C07D217/04 ,  C07D217/24 ,  A61K31/472 ,  A61P25/16 ,  A61P25/28 ,  A61P43/00 ,  C07D405/06

Abstract: This invention relates to isoquinolino derivatives of the general Formula (I) wherein Y is >C=O or CH2-, Z is >C=O or CH2-, and R1, R2 and m are as defined in the specification, as well as their pharmaceutically acceptable salts. The invention further relates to medicaments containing these compounds, a process for their preparation as well as their use for preparation of medicaments for the treatment or prevention of diseases in which MAO-B inhibitors might be beneficial.

公开(公告)号：ES2329354T3

公开(公告)日：2009-11-25

申请号：ES03725018

申请日：2003-04-14

Applicant: HOFFMANN LA ROCHE

Inventor： CESURA ANDREA ,  RODRIGUEZ SARMIENTO ROSA MARIA ,  SCALONE MICHELANGELO ,  THOMAS ANDREW WILLIAM ,  WYLER RENE

IPC: C07D217/04 ,  C07D217/24 ,  A61K31/472 ,  A61P25/16 ,  A61P25/28 ,  A61P43/00 ,  C07D405/06

Abstract: Compuestos de fórmula general **(Ver fórmula)** en donde Y es >C=O o -CH2-; Z es >C=O o -CH2-; R1 es hidrógeno; o es un grupo de fórmula a -CR3R4R5 (a) en donde R3 es -(CH2)n-CO-NR6R7; -(CH2)n-COOR8; -CHR9-COOR8; -(CH2)n-CN; -(CH2)P-OR8; -(CH2)n-NR6R7, -(CH2)n-CF3; -(CH2)n-NH-COR9; -(CH2)n-NH-COOR8; -(CH2)n-tetrahidrofuranilo; -(CH2)p-SR8; -(CH2)p-SO-R9; o -(CH2)n-CS-NR5R6; R4 es hidrógeno, C1-C6-alquilo, -(CH2)P-OR8, -(CH2)p-SR8, o bencilo; R5 es hidrógeno, C1-C6-alquilo, -(CH2)P-OR8, -(CH2)p-SR8, o bencilo; R6 y R7 son independientemente el uno del otro hidrógeno o C1-C6-alquilo; R8 es hidrógeno o C1-C6-alquilo; R9 es C1-C6-alquilo; m es 1, 2 ó 3; n es 0, 1 ó 2; y p es 1 ó 2; R2 es independientemente seleccionado de halógeno, halógeno-(C1-C6)-alquilo, ciano, C1-C6-alcoxilo o halógeno- (C1-C6)-alcoxilo; así como sus sales farmacéuticamente aceptables, con la condición de que se excluye éster terbutílico del ácido 3-[6-(4-ciano-benciloxi)-1-oxo-3,4-dihidro-1H-isoquinolin- 2-il]-propionico, éster terbutílico del ácido 3-[6-(4-ciano-benciloxi)-1-oxo-3,4-dihidro-1H-isoquinolin-2-il]- pentanoico, éster terbutílico del ácido 3-[6-(4-ciano-benciloxi)-1-oxo-3,4-dihidro-1H-isoquinolin-2-il]-hexanoico, éster terbutílico del ácido 3-[6-(4-ciano-benciloxi)-1-oxo-3,4-dihidro-1H-isoquinolin-2-il]-heptanoico, éster terbutílico del ácido 3-[6-(4-ciano-benciloxi)-1-oxo-3,4-dihidro-1H-isoquinolin-2-il]-octanoico, éster terbutílico del ácido 3-[6- (4-ciano-benciloxi)-1-oxo-3,4-dihidro-1H-isoquinolin-2-il]-nonanoico, éster terbutílico del ácido 3-[6-(4-ciano-benciloxi)- 1-oxo-3,4-dihidro-1H-isoquinolin-2-il]-6-etoxi-hexanoico, éster terbutílico del ácido 3-[6-(4-ciano-benciloxi)- 1-oxo-3,4-dihidro-1H-isoquinolin-2-il]-6-metoxi-hexanoico, éster terbutílico del ácido [6-(4-ciano-benciloxi)-1-oxo- 3,4-dihidro-1H-isoquinolin-2-il]-acético, y éster terbutílico del ácido [6-(4-ciano-benciloxi)-3,4-dihidro-1H-isoquinolin- 2-il]-acético. 2. Compuest

公开(公告)号：AU2003226680B2

公开(公告)日：2009-05-07

申请号：AU2003226680

申请日：2003-03-20

Applicant: HOFFMANN LA ROCHE

Inventor： THOMAS ANDREW WILLIAM ,  CESURA ANDREA ,  WYLER RENE ,  SARMIENTO ROSA MARIA RODRIGUEZ

IPC: C07D209/48 ,  A61K31/4035 ,  A61K31/42 ,  A61K31/437 ,  A61K31/454 ,  A61K31/5377 ,  A61P25/28 ,  A61P43/00 ,  C07D401/04 ,  C07D405/06 ,  C07D407/06 ,  C07D409/06 ,  C07D413/04 ,  C07D413/06 ,  C07D471/04

Abstract: This invention relates to phthalimido derivatives of the formula wherein X is -N- or -CH-, and R 1 to R 4 and m are as defined in the specification, as well as their pharmaceutically acceptable salts. The invention further relates to pharmaceutical compositions containing these compounds, a method of treating a disease by administering a therapeutically effective amount of at least one of these compounds, and a process for their preparation for the treatment or prevention of diseases in which MAO-B inhibitors might be beneficial.

公开(公告)号：AU2003227614B2

公开(公告)日：2008-06-26

申请号：AU2003227614

申请日：2003-04-14

Applicant: HOFFMANN LA ROCHE

Inventor： CESURA ANDREA ,  SARMIENTO ROSA MARIA RODRIGUEZ ,  SCALONE MICHELANGELO ,  WYLER RENE ,  THOMAS ANDREW WILLIAM

IPC: C07D217/04 ,  A61K31/472 ,  A61P25/16 ,  A61P25/28 ,  A61P43/00 ,  C07D217/24 ,  C07D405/06

Abstract: Disclosed are isoquinolino derivatives of the formulawherein Y is >C=O or -CH2-, Z is >C=O or -CH2-, and R , R and m are as defined herein as well as the pharmaceutically acceptable salts thereof. These compounds are MAO-B selective inhibitors useful, inter alia, in the treatment of Alzheimer's disease and/or senile dementia.