公开(公告)号：DK0970957T3

公开(公告)日：2001-12-03

申请号：DK99110943

申请日：1999-06-07

Applicant: HOFFMANN LA ROCHE

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

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 ,  A61K31/445

Abstract: The invention relates to compounds of the general formula wherein R is C6-12-cycloalkyl, optionally substituted by lower alkyl or C(O)O lower alkyl, indan-1-yl or indan-2-yl, optionally substituted by lower alkyl; acenaphthen-1-yl; bicycloÄ3.3.1Ünon-9-yl, octahydro-inden-2-yl; 2,3-dihydro-1H-phenalen-1-yl; 2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl, decahydro-azulen-2-yl; bicycloÄ6.2.0Üdec-9-yl; decahydro-naphthalen-1-yl, decahydro-naphthalen-2-yl; tetrahydro-naphthalen-1-yl, tetrahydro-naphthalen-2-yl or 2-oxo-1,2-diphenyl-ethyl; R is =O or hydrogen, R is hydrogen, isoindolyl-1,3-dione, lower alkoxy, lower alkyl, amino, benzyloxy, -CH2OR or -CH2N(R )2; R is hydrogen or -CH2OR ; R is hydrogen or lower alkyl; A &cir& is cyclohexyl or phenyl, optionally substituted by lower alkyl, halogen or alkoxy; to racemic mixtures and their corresponding enantiomers and or pharmaceutically acceptable acid addition salts thereof. The compounds of the present invention are agonists and/or antagonists of the orphamin FQ (OFQ) receptor and therefore useful in the treatment of diseases, related to this receptor.

公开(公告)号：DE69900220D1

公开(公告)日：2001-09-20

申请号：DE69900220

申请日：1999-06-07

Applicant: HOFFMANN LA ROCHE

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

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 ,  A61K31/445

Abstract: The invention relates to compounds of the general formula wherein R is C6-12-cycloalkyl, optionally substituted by lower alkyl or C(O)O lower alkyl, indan-1-yl or indan-2-yl, optionally substituted by lower alkyl; acenaphthen-1-yl; bicycloÄ3.3.1Ünon-9-yl, octahydro-inden-2-yl; 2,3-dihydro-1H-phenalen-1-yl; 2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl, decahydro-azulen-2-yl; bicycloÄ6.2.0Üdec-9-yl; decahydro-naphthalen-1-yl, decahydro-naphthalen-2-yl; tetrahydro-naphthalen-1-yl, tetrahydro-naphthalen-2-yl or 2-oxo-1,2-diphenyl-ethyl; R is =O or hydrogen, R is hydrogen, isoindolyl-1,3-dione, lower alkoxy, lower alkyl, amino, benzyloxy, -CH2OR or -CH2N(R )2; R is hydrogen or -CH2OR ; R is hydrogen or lower alkyl; A &cir& is cyclohexyl or phenyl, optionally substituted by lower alkyl, halogen or alkoxy; to racemic mixtures and their corresponding enantiomers and or pharmaceutically acceptable acid addition salts thereof. The compounds of the present invention are agonists and/or antagonists of the orphamin FQ (OFQ) receptor and therefore useful in the treatment of diseases, related to this receptor.

公开(公告)号：SG83135A1

公开(公告)日：2001-09-18

申请号：SG1999002947

申请日：1999-06-09

Applicant: HOFFMANN LA ROCHE

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

IPC: 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 ,  C07D401/04 ,  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: The present invention relates to compounds of the general formula wherein R is C6-10-cycloalkyl, optionally substituted by lower alkyl or -C(O)O-lower alkyl; decahydro-naphthalen-1-yl; decahydro-naphthalen-2-yl; indan-1-yl or indan-2-yl, optionally substituted by lower alkyl; decahydro-azulen-2-yl; bicycloÄ6.2.0Üdec-9-yl; acenaphthen-1-yl; 2,3-dihydro-1H-phenalen-1-yl; 2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl or octahydro-inden-2-yl; R is hydrogen; lower alkyl; =O or phenyl, optionally substituted by lower alkyl, halogen or alkoxy; A &cir& is cyclohexyl or phenyl, optionally substituted by lower alkyl, halogen or alkoxy; X is -CH(OH)-; -C(O)-; -CHR -; -CR =; -O-; -S-; -CH(COOR )- or - C(COOR )=; Y is -CH2-; -CH=; -CH(COOR )-, -C(COOR )=; or -C(CN)-; R is hydrogen or lower alkoxy; R is lower alkyl, cycloalkyl, phenyl, or benzyl and either a or b is optionally an additional bond, and to pharmaceutically acceptable acid addition salts thereof. The compounds are agonists and/or antagonists of the orphanin FQ (QFQ) receptor and therefore useful in the treatment of diseases, related to this receptor.

公开(公告)号：NO310026B1

公开(公告)日：2001-05-07

申请号：NO980332

申请日：1998-01-26

Applicant: HOFFMANN LA ROCHE

Inventor： ADAM GEO ,  CESURA ANDREA ,  GALLEY GUIDO ,  JENCK FRANCOIS ,  MONSMA JR 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 ,  A61K31/44

Abstract: The present invention relates to compounds of the formula wherein R and R are, independently from each other, hydrogen, lower alkyl, lower alkoxy or halogen; R is phenyl, optionally substituted by lower alkyl,CF3, lower alkoxy or halogen; and R is hydrogen, lower alkyl, lower alkenyl, -C(O)-lower alkyl, -C(O)-phenyl, lower alkyl-C(O)-phenyl, lower alkylen-C(O)O-lower alkyl, lower alkantriyl-di-C(O)O-lower alkyl, hydroxy-lower alkyl, lower alkyl-O-lower alkyl, lower alkyl-CH(OH)CF3, phenyl or benzyl, R and R are, independently from each other, hydrogen, phenyl, lower alkyl or di-lower alkyl or may form together a phenyl ring, and R and one of R or R may form together a saturated or unsaturated 6 membered ring, A is a 4 - 7 membered saturated ring which may contain a heteroatom such as O or S, and to pharmaceutically acceptable acid addition salts thereof which are agonists and/or antagonists of the OFQ receptor.

公开(公告)号：SG79259A1

公开(公告)日：2001-03-20

申请号：SG1999003066

申请日：1999-06-09

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 ,  A61K31/445

Abstract: The invention relates to compounds of the general formula wherein R is C6-12-cycloalkyl, optionally substituted by lower alkyl or C(O)O lower alkyl, indan-1-yl or indan-2-yl, optionally substituted by lower alkyl; acenaphthen-1-yl; bicycloÄ3.3.1Ünon-9-yl, octahydro-inden-2-yl; 2,3-dihydro-1H-phenalen-1-yl; 2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl, decahydro-azulen-2-yl; bicycloÄ6.2.0Üdec-9-yl; decahydro-naphthalen-1-yl, decahydro-naphthalen-2-yl; tetrahydro-naphthalen-1-yl, tetrahydro-naphthalen-2-yl or 2-oxo-1,2-diphenyl-ethyl; R is =O or hydrogen, R is hydrogen, isoindolyl-1,3-dione, lower alkoxy, lower alkyl, amino, benzyloxy, -CH2OR or -CH2N(R )2; R is hydrogen or -CH2OR ; R is hydrogen or lower alkyl; A &cir& is cyclohexyl or phenyl, optionally substituted by lower alkyl, halogen or alkoxy; to racemic mixtures and their corresponding enantiomers and or pharmaceutically acceptable acid addition salts thereof. The compounds of the present invention are agonists and/or antagonists of the orphamin FQ (OFQ) receptor and therefore useful in the treatment of diseases, related to this receptor.

公开(公告)号：UY24865A1

公开(公告)日：2000-12-29

申请号：UY24865

申请日：1998-01-29

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: Compuestos de fórmula general (I), representada en la figura 1, y sales de adición de los mismos, en particular derivados de la 8-sustituida-1,3,8-triazospiro[4.5]-4-ona,donde: R1 y R2 son independientemente el uno del otro, hidrógeno, alquilo, alcoxi o halógeno; R3 es fenilo, alquilo opcionalmente sustituido, CF3, alcoxi o halógeno; A es un anillo saturado de 4 a 7 miembros; R5 y R6 son independientemente el uno del otro, hidrógeno, fenilo, alquilo o di-alquilo o juntos pueden formar un anillo fenilo, y R5 y uno de R1 y R2 pueden formar juntos un anillo saturado o no saturado de 6 miembros; cn la condición que dicho compuesto de fórmula general (I) no sea 8-(8-metoxi-1,2,3,4-tetrahidro-2-naftalenil)-1-fenil-1,3,8-triaza-spiro[4,5]decan-4-ona. Ejemplos no limitantes de compuestos de fórmula general (I): 8-(5,8-dicloro-1,2,3,4-tetrahidro-naftil-2)-3-metil-1-fenil-1,3,8-triaza-spiro[4,5]decan-4-ona; éster metílico de ácido [8-(5,8-dicloro-1,2,3,4-tetrahidro-naftil-2)-4-oxo-1-fenil-1,3,8-triaza-spiro[4,5]dec-3-il] acético. Se incluyen medicamentos que los contienen para el tratamiento de enfermedades relacionadas con el receptor de orfaniana FQ(OFQ), que incluye trastornos siquiátricos, neurológicos y fisiológicos; como por ejemplo trastornos de ansiedad y Alzheimer.

公开(公告)号：PE20000548A1

公开(公告)日：2000-07-15

申请号：PE00048799

申请日：1999-06-08

Applicant: HOFFMANN LA ROCHE

Inventor： CESURA ANDREA ,  WICHMANN JURGEN ,  ADAM GEO ,  KOLCZEWSKI SABINE ,  JENCK FRANCOIS ,  ROVER STEPHAN

IPC: C07D401/00 ,  A61K31/00 ,  A61K31/438 ,  A61K31/445 ,  A61P3/04 ,  A61P9/10 ,  A61P25/04 ,  A61P25/08 ,  A61P25/18 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/30 ,  C07D471/10

Abstract: SE REFIERE A DERIVADOS DE DIAZA-ESPIRO[3.5]NONANO DE FORMULA I, DONDE R1 ES CICLOALQUILO C6-C12, INDAN-1-ILO, ACENAFTEN-1-ILO, BICICLO[3.3.1]NON-9-ILO, OCTAHIDRO-INDEN-2-ILO, 2,3-DIHIDRO-1H-FENALEN-1-ILO, ENTRE OTROS; R2 ES =O o H; R3 ES H, ISOINDOLIL-1,3-DIONA, ALCOXILO, ALQUILO, AMINO, BENCILOXILO, -CH2OR5, -CH2N(R5)2; R4 ES H, -CH2OR5; R5 ES H o ALQUILO; EL ANILLO A ES CICLOHEXILO, FENILO OPCIONALMENTE SUSTITUIDO CON ALQUILO, HALOGENO, ALCOXILO. SON COMPUESTOS PREFERIDOS 3,3-BIS-HIDROXIMETIL-7-(CIS-4-ISOPROPIL-CICLOHEXIL)-1-FENIL-1,7-DIAZA-ESPIRO[3.5]NONAN-2-ONA, 7-(CIS-4-ISOPROPIL-CICLOHEXIL)-1-FENIL-1,7-DIAZA-ESPIRO[3,5]NONAN-2-ONA, ENTRE OTROS. TAMBIEN SE REFIERE A UN PROCEDIMIENTO PARA LA PREPARACION. EL COMPUESTO I ES UN AGONISTA/ANTAGONISTA DEL RECEPTOR DE LA ORFANINA OFQ POR LO QUE PUEDE SER UTIL PARA EL TRATAMIENTO DE TRASTORNOS PSIQUIATRICOS, NEUROLOGICOS, FISIOLOGICOS, TRASTORNOS DE ANSIEDAD, ESTRES, DEPRESION, TRAUMAS, EPILEPSIA, CONVULSIONES, CONDICIONES DE DOLOR AGUDO O CRONICO

公开(公告)号：NZ333159A

公开(公告)日：2000-06-23

申请号：NZ33315998

申请日：1998-12-03

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 ,  A61K31/445

Abstract: 1,3,8-triaza-spiro[4,5]decan-4-on derivatives of the formula 1 where: A is a ring system of (a) C5-15 cycloalkyl optionally substituted by lower alkyl, trifluoromethyl, phenyl, C5-7 cycloalkyl, spiro-undecan-alkyl or by 2-norbornyl, or is one of the following groups (b)-(d), (e) dodecahydro-acenaphthylen-lyl (f) bicyclo[6.2.0]dec-9-yl (g) and bicyclononan-9-yl R1 is H, lower alkyl, Hal, lower alkoxy, CF3, lower alkyl-phenyl or C5-7 cycloalkyl; R2 is H, lower alkyl, phenyl or lower alkyl-phenyl; R3 is H, lower alkyl, benzyl, lower alkyl-phenyl, lower alkyl-diphenyl and other cyclic rings R4 us H, lower alkyl or nitrilo; R5 and R6 are H, lower alkyl or taken together and with the carbon atoms to which they are joined form a phenyl ring R7 is H or lower alkyl; The dotted line is an optional bond and n is 1-4 Process for preparation and use for the treatment of diseases related to Orphanin (OFQ) receptor is described.

公开(公告)号：ID23304A

公开(公告)日：2000-04-05

申请号：ID990543

申请日：1999-06-08

Applicant: HOFFMANN LA ROCHE

Inventor： ADAM GEO ,  CESURA ANDREA ,  JENCK FRANCOIS ,  KOLCZEWSKI SABINE ,  ROVER STEPHAN ,  WICHMANN JURGEN

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 ,  C07D205/04 ,  C07D211/02 ,  A61K31/40

Abstract: The invention relates to compounds of the general formula wherein R is C6-12-cycloalkyl, optionally substituted by lower alkyl or C(O)O lower alkyl, indan-1-yl or indan-2-yl, optionally substituted by lower alkyl; acenaphthen-1-yl; bicycloÄ3.3.1Ünon-9-yl, octahydro-inden-2-yl; 2,3-dihydro-1H-phenalen-1-yl; 2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl, decahydro-azulen-2-yl; bicycloÄ6.2.0Üdec-9-yl; decahydro-naphthalen-1-yl, decahydro-naphthalen-2-yl; tetrahydro-naphthalen-1-yl, tetrahydro-naphthalen-2-yl or 2-oxo-1,2-diphenyl-ethyl; R is =O or hydrogen, R is hydrogen, isoindolyl-1,3-dione, lower alkoxy, lower alkyl, amino, benzyloxy, -CH2OR or -CH2N(R )2; R is hydrogen or -CH2OR ; R is hydrogen or lower alkyl; A &cir& is cyclohexyl or phenyl, optionally substituted by lower alkyl, halogen or alkoxy; to racemic mixtures and their corresponding enantiomers and or pharmaceutically acceptable acid addition salts thereof. The compounds of the present invention are agonists and/or antagonists of the orphamin FQ (OFQ) receptor and therefore useful in the treatment of diseases, related to this receptor.

公开(公告)号：AU5858199A

公开(公告)日：2000-03-27

申请号：AU5858199

申请日：1999-09-02

Applicant: HOFFMANN LA ROCHE

Inventor： CESURA ANDREA ,  HOFFMANN TORSTEN ,  ROEVER STEPHAN ,  WICHMANN JURGEN

IPC: C07D211/14 ,  A61K31/445 ,  A61K31/451 ,  A61P3/04 ,  A61P3/12 ,  A61P9/00 ,  A61P25/04 ,  A61P25/08 ,  A61P25/16 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/30 ,  C07D211/20 ,  C07D211/22 ,  C07D211/42

Abstract: The present invention relates to compounds of general formula (I), wherein R is tetrahydronaphtyl; or -(CH2)n-C6H5-R wherein n is 0-4 and R is H, lower alkyl, or lower alkoxy; or C5-C12 cycloalkyl, optionally substituted by lower alkyl; R is H, OH, lower alkoxy, lower alkenyloxy or lower alkyl; R is C5-C7 cycloalkyl or phenyl, optionally substituted by OH, halogen, lower alkoxy, lower alkenyloxy, lower alkyl or -O-(CH2)n-C6H5 wherein n is 0-3; and their pharmaceutically acceptable acid addition salts. The compounds of general formula (I) are suitable for the treatment of memory and attention deficits, psychiatric, neurological and physiological disorders, such as anxiety and stress disorders, depression, memory loss due to Alzheimer's disease or other dementias such as vascular dementia and AIDS dementia complex, Parkinson's disease, epilepsy and convulsions, acute and/or chronic pain conditions, withdrawal symptoms of addictive drugs and reduction of their abuse/craving, control of water balance, Na excretion, arterial blood pressure disorders and metabolic disorders such as obesity.