公开(公告)号：KR20180072827A

公开(公告)日：2018-06-29

申请号：KR20187016509

申请日：2015-04-01

Applicant: HOFFMANN LA ROCHE ,  EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH

Inventor： GOBBI LUCA ,  GRETHER UWE ,  NETTEKOVEN MATTHIAS ,  ROEVER STEPHAN ,  ROGERS EVANS MARK ,  SLAVIK ROGER

IPC: C07D213/81 ,  A61K31/44 ,  A61K31/4439 ,  C07D401/04 ,  C07D401/14 ,  C07D405/14 ,  C07D413/14 ,  C07D417/12 ,  C07D491/10

CPC classification number: C07D213/81 ,  C07D401/04 ,  C07D401/14 ,  C07D405/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/06 ,  C07D417/12 ,  C07D417/14 ,  C07D491/10 ,  C07D491/107 ,  C07K5/06139

Abstract: 본발명은하기화학식 I의화합물에관한것이다: 화학식 I상기식에서, R내지 R는명세서및 청구범위에정의된바와같다. 화학식 I의화합물은카나비노이드수용체 2(CB2)의작용제이고, 이에따라, 통증, 죽상경화증, 염증등과같은다양한질병의치료에유용하다.

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：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：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：US20150376192A1

公开(公告)日：2015-12-31

申请号：US14844991

申请日：2015-09-03

Applicant: Hoffmann-La Roche Inc.

Inventor： UWE GRETHER ,  ATSUSHI KIMBARA ,  NETTEKOVEN MATTHIAS ,  RICKLIN FABIENNE ,  ROEVER STEPHAN ,  MARK ROGERS-EVANS ,  TANJA SCHULZ-GASCH

IPC: C07D487/04 ,  C07D471/04

CPC classification number: A61K31/519 ,  C07D471/04 ,  C07D473/04 ,  C07D487/04

Abstract: The invention relates to a compound of formula (I) wherein A1 to A3 and R1 to R3 are defined as in the description and in the claims. The compound of formula (I) can be used as a medicament.

Abstract translation: 本发明涉及式（I）化合物，其中A 1至A 3和R 1至R 3如在说明书和权利要求书中所定义。 式（I）化合物可以用作药物。

公开(公告)号：WO2006077025A3

公开(公告)日：2006-09-08

申请号：PCT/EP2006000126

申请日：2006-01-10

Applicant: HOFFMANN LA ROCHE ,  VERNALIS RES LTD ,  BENTLEY JONATHAN MARK ,  DAWSON CLAIRE ELIZABETH ,  GUBA WOLFGANG ,  HEBEISEN PAUL ,  MONCK NATHANIEL ,  PRATT ROBERT MARK ,  RICHTER HANS ,  ROEVER STEPHAN ,  RUSTON VICKI

Inventor： BENTLEY JONATHAN MARK ,  DAWSON CLAIRE ELIZABETH ,  GUBA WOLFGANG ,  HEBEISEN PAUL ,  MONCK NATHANIEL ,  PRATT ROBERT MARK ,  RICHTER HANS ,  ROEVER STEPHAN ,  RUSTON VICKI

IPC: C07D265/30 ,  A61K31/5375 ,  A61P3/04 ,  A61P3/10

CPC classification number: C07D265/30

Abstract: The present invention refers to chemical compounds of formula (I) as well as pharmaceutically acceptable salts and esters thereof, wherein R 1 to R 5 have the significance given in claim 1. These compounds can be used for the preparation of medicaments.

Abstract translation: 本发明涉及式（I）的化学化合物及其药学上可接受的盐和酯，其中R 1至R 5具有权利要求1中给出的含义。 这些化合物可以用于制备药物。

公开(公告)号：WO02072584A2

公开(公告)日：2002-09-19

申请号：PCT/EP0202443

申请日：2002-03-06

Applicant: HOFFMANN LA ROCHE ,  VERNALIS RES LTD

Inventor： HEBEISEN PAUL ,  MATTEI PATRIZIO ,  MULLER MARC ,  RICHTER HANS ,  ROEVER STEPHAN ,  TAYLOR SVEN

IPC: A61K31/337 ,  A61K31/4985 ,  A61P3/00 ,  A61P3/04 ,  A61P3/10 ,  A61P7/02 ,  A61P9/00 ,  A61P11/00 ,  A61P13/02 ,  A61P25/00 ,  A61P25/06 ,  A61P25/08 ,  A61P25/18 ,  A61P25/20 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/30 ,  A61P25/32 ,  A61P29/00 ,  A61P43/00 ,  C07D487/04

CPC classification number: C07D487/04

Abstract: The present invention refers to chemical compounds of formula (I) as well as pharmaceutically acceptable salts, solvates and esters thereof, wherein R to R have the significance given in the description and the claims. The compounds can be used in the form of pharmaceutical preparations for the treatment or prevention of disorders of the central nervous system, damage to the central nervous system, cardiovascular disorders, gastrointestinal disorders, diabetes insipidus, type II diabetes, obesity and sleep apnoea.

Abstract translation: 本发明涉及式（I）的化合物及其药学上可接受的盐，溶剂合物和酯，其中R 1至R 7具有在说明书和权利要求书中给出的含义。 化合物可以以用于治疗或预防中枢神经系统疾病，中枢神经系统损害，心血管疾病，胃肠道疾病，尿崩症，II型糖尿病，肥胖症和睡眠呼吸暂停的药物制剂的形式使用。

公开(公告)号：WO2009021868A3

公开(公告)日：2009-04-09

申请号：PCT/EP2008060213

申请日：2008-08-04

Applicant: HOFFMANN LA ROCHE ,  DEHMLOW HENRIETTA ,  KUHN BERND ,  OBST SANDER ULRIKE ,  ROEVER STEPHAN ,  SCHULZ-GASCH TANJA ,  WRIGHT MATTHEW ,  WYLER RENE

Inventor： DEHMLOW HENRIETTA ,  KUHN BERND ,  OBST SANDER ULRIKE ,  ROEVER STEPHAN ,  SCHULZ-GASCH TANJA ,  WRIGHT MATTHEW ,  WYLER RENE

IPC: C07D241/02 ,  A61K31/497 ,  A61P1/16 ,  A61P1/18 ,  A61P3/06 ,  A61P3/10 ,  C07D401/06 ,  C07D401/12 ,  C07D403/12 ,  C07D409/12 ,  C07D413/12

CPC classification number: C07D241/02 ,  C07D401/06 ,  C07D401/12 ,  C07D403/12 ,  C07D409/12 ,  C07D413/12

Abstract: The invention is concerned with novel piperazine amide derivatives of formula (I) wherein R1 to R11, W, X and Y are as defined in the description and in the claims, as well as physiologically acceptable salts thereof. These compounds bind to LXR alpha and LXR beta and can be used as medicaments.

Abstract translation: 本发明涉及式（I）的新型哌嗪酰胺衍生物，其中R 1至R 11，W，X和Y如说明书和权利要求书中所定义，以及其生理学上可接受的盐。 这些化合物与LXRα和LXRβ结合，可用作药物。

公开(公告)号：WO2008040649A3

公开(公告)日：2008-05-29

申请号：PCT/EP2007060090

申请日：2007-09-24

Applicant: HOFFMANN LA ROCHE ,  DIETZ MICHEL ,  GRUENER SABINE ,  HEBEISEN PAUL ,  MEYER REIGNER SYLVIE C ,  NETTEKOVEN MATTHIAS ,  PUELLMANN BERND ,  ROEVER STEPHAN ,  ULLMER CHRISTOPH

Inventor： DIETZ MICHEL ,  GRUENER SABINE ,  HEBEISEN PAUL ,  MEYER REIGNER SYLVIE C ,  NETTEKOVEN MATTHIAS ,  PUELLMANN BERND ,  ROEVER STEPHAN ,  ULLMER CHRISTOPH

IPC: C07D241/26 ,  A61K31/4965 ,  A61K31/497 ,  A61P9/00 ,  A61P9/10 ,  A61P11/06 ,  A61P29/00 ,  A61P37/00 ,  C07D401/04 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12

CPC classification number: C07D241/26 ,  C07D401/04 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12

Abstract: The present invention relates to compounds of the formula (I) wherein R 1 to R 4 are as defined in the description and claims, and pharmaceutically acceptable salts thereof. The compounds are useful for the treatment and/or prophylaxis of diseases which are associated with the modulation of CB 2 receptors.

Abstract translation: 本发明涉及式（I）的化合物，其中R 1至R 4如在说明书和权利要求书中所定义，及其药学上可接受的盐。 该化合物可用于治疗和/或预防与调节CB 2受体相关的疾病。