公开(公告)号：JP2000053680A

公开(公告)日：2000-02-22

申请号：JP16397599

申请日：1999-06-10

Applicant: HOFFMANN LA ROCHE

Inventor： ADAM GEO ,  DAUTZENBERG FRANK ,  KOLCZEWSKI SABINE ,  ROVER STEPHAN ,  WICHMANN JUERGEN

IPC: C07D401/14 ,  A01N43/42 ,  A61K31/00 ,  A61K31/395 ,  A61K31/435 ,  A61K31/438 ,  A61K31/44 ,  A61K31/445 ,  A61K31/505 ,  A61K31/535 ,  A61P3/04 ,  A61P3/12 ,  A61P9/12 ,  A61P25/04 ,  A61P25/08 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/30 ,  A61P43/00 ,  C07D20060101 ,  C07D209/00 ,  C07D221/00 ,  C07D471/10 ,  C07D471/20 ,  C07D487/20 ,  C07D498/10 ,  C07D513/10

Abstract: PROBLEM TO BE SOLVED: To obtain a new compound useful for treating diseases related to orphanin FQ receptor including anxiety, stress disorder, depression, trauma, etc. SOLUTION: This compound is shown by formula I (R1 is a 5-12C cycloalkyl substitutable with a lower alkyl or the like; R2 and R3 are each H, OH or the like; R4 is H or the like; R5 is H or the like), preferably (3'aS,6'aR)-5'- ethyl-2'-phenyl-1-[(R)-1,2,3,4-tetrahydro-naphthalen-1-yl]-hexahydro- spiro[piperidine-4,1'-pyrrolo[3,4-c]pyrrole], etc. The compound of formula I obtained, as one favorable production process, by reducing a compound of formula II e.g. (3'aR,6'aS)-5'-ethyl-1-[(R)-1,2,3,4-tetrahydro-naphthalen-1-yl]-2'- phenyl-hexahydro-spiro[piperidine-4,1'-pyrrolo[3,4-c]pyrrole]-4',6'-dione or the like).

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：CA2274204C

公开(公告)日：2009-09-15

申请号：CA2274204

申请日：1999-06-09

Applicant: HOFFMANN LA ROCHE

Inventor： ROVER STEPHAN ,  ADAM GEO ,  DAUTZENBERG FRANK ,  WICHMANN JURGEN ,  KOLCZEWSKI SABINE

IPC: C07D401/14 ,  C07D471/20 ,  A01N43/42 ,  A61K31/00 ,  A61K31/395 ,  A61K31/435 ,  A61K31/438 ,  A61K31/44 ,  A61K31/445 ,  A61K31/505 ,  A61K31/535 ,  A61P3/04 ,  A61P3/12 ,  A61P9/12 ,  A61P25/00 ,  A61P25/04 ,  A61P25/08 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/30 ,  A61P43/00 ,  C07D20060101 ,  C07D209/00 ,  C07D221/00 ,  C07D471/10 ,  C07D487/20 ,  C07D498/10 ,  C07D513/10

Abstract: The present invention relates to compounds of the general formula (see formula I) wherein the substituents are described in the application and to pharmaceutically acceptable acid addition salts thereof. The compound of the invention are useful in the treatment of diseases related to the orphanin FQ (OFQ) receptor, which include psychiatric, neurological and physiological disorders, such as anxiety and stress disorders, depression, trauma, memory loss due to Alzheimer's disease or other dementias, deficits in cognition and learning, epilepsy and convulsions, acu te and/or chronic pain conditions, and symptoms of addictive drug withdrawal, control of water balance, Na+ excretion, arterial blood pressure disorders a nd metabolic disorders such as obesity.

公开(公告)号：CO5150201A1

公开(公告)日：2002-04-29

申请号：CO99055221

申请日：1999-09-01

Applicant: HOFFMANN LA ROCHE

Inventor： CESURA ANDREA ,  HOFFMANN TORSTEN ,  ROVER 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: Compuestos de la fórmula general en dondeR1 es tetrahidronaftilo;o -(CH2)nC6H5-R4 en donde n es 0-4 y R4 es H, alquilo de C1-C6 o alcoxilo de C1-C6;o cicloalquilo de C5-C12, opcionalmente sustituido por alquilo de C1-C6,R2 es H, OH, alcoxilo de C1-C6, alqueniloxilo de C1-C6, o alquilo de C1-C6;R3 es cicloalquilo de C5-C7 o fenilo, opcionalmente sustituido por OH, halógeno, alcoxilo de C1-C6, alqueniloxilo de C1-C6, alquilo de C1-C6, u -0-(CH2)n-C6H5 en donde n es 0-3;y a sus sales de adición de ácido farmacéuticamente aceptables.

公开(公告)号：FR2744447B1

公开(公告)日：2000-09-29

申请号：FR9701081

申请日：1997-01-31

Applicant: HOFFMANN LA ROCHE

Inventor： ALANINE ALEXANDER ,  BOURSON ANNE ,  BUTTELMANN BERND ,  FISCHER GUNTHER ,  HEITZ NEIDHART MARIE PAULE ,  MUTEL VINCENT ,  PINARD EMMANUEL ,  ROVER STEPHAN ,  TRUBE GERHARD ,  WYLER RENE

IPC: C07D217/16 ,  A61K31/47 ,  A61K31/472 ,  A61K31/473 ,  A61K31/4741 ,  A61P25/00 ,  A61P25/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/20 ,  A61P25/22 ,  A61P25/24 ,  A61P25/26 ,  A61P25/28 ,  A61P43/00 ,  C07D217/18 ,  C07D217/20 ,  C07D217/24 ,  C07D221/00 ,  C07D221/06 ,  C07D221/12 ,  C07D491/04 ,  C07D491/056

Abstract: The present invention relates to the use of tetrahydroisoquinoline derivatives of the general formula wherein A is aryl R1 is hydrogen, hydroxy, lower alkyl, lower alkoxy, R-CO- or R-COO-, wherein R is lower alkyl; R2 is hydrogen, lower alkyl or cycloalkyl R3-R7 are independently hydrogen, lower alkyl, lower alkoxy, hydroxy or R3 and R4 taken together are -(CH2)n- or R6 and R7 taken together are -OCH2O- and n is 3 or 4, as well as pharmaceutically acceptable salts for the manufacture of medicaments for the control or treatment of diseases which represent therapeutic indications for NMDA receptor subtype specific blockers.

公开(公告)号：PE20000549A1

公开(公告)日：2000-07-24

申请号：PE00048599

申请日：1999-06-08

Applicant: HOFFMANN LA ROCHE

Inventor： WICHMANN JURGEN ,  ADAM GEO ,  ROVER STEPHAN ,  DAUTZENBERG FRANK ,  KOLCZEWSKI SABINE

IPC: C07D401/14 ,  A01N43/42 ,  A61K31/00 ,  A61K31/395 ,  A61K31/435 ,  A61K31/438 ,  A61K31/44 ,  A61K31/445 ,  A61K31/505 ,  A61K31/535 ,  A61P3/04 ,  A61P3/12 ,  A61P9/12 ,  A61P25/04 ,  A61P25/08 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/30 ,  A61P43/00 ,  C07D20060101 ,  C07D209/00 ,  C07D221/00 ,  C07D471/10 ,  C07D471/20 ,  C07D487/20 ,  C07D498/10 ,  C07D513/10

Abstract: SE REFIERE A ESPIRO[PIPERIDIN-4,1`-PIRROLO[3,4-c]PIRROL] DE FORMULA I, DONDE R1 ES CICLOALQUILO C5-C12 OPCIONALMENTE SUSTITUIDO CON ALQUILO, DECAHIDRO-NAFTALEN-1-ILO, INDAN-1-IL, DECAHIDRO-AZULEN-2-ILO, BICICLO[6.2.0]DEC-9-ILO, ACENAFTEN-1-ILO, BICICLO[3.3.1]NON-9-ILO, 2,3-DIHIDRO-1H-FENALEN-1-ILO, ENTRE OTROS; R2 Y R3 SON H, OH, ALQUILO, =O, FENILO OPCIONALMENTE SUSTITUIDO CON ALQUILO, HALOGENO, ALCOXILO; R4 ES H, ALQUILO, (CH2)nCHOHCF3, -(CH2)n-CICLOALQUILO C3-C6, FENILO, BENCILO, TETRAHIDROFURAN-3-ILO, -(CH2)nOCH2C6H5, -(CH2)nMORFOLINILO, 3-METIL-OXETAN-3-IL-METILO, -(CH2)nCH2OH, -SO2-ALQUILO, -CO-ALQUILO, -COCF3, ENTRE OTROS; R5 ES H, HALOGENO, ALQUILO, TRIFLUOROMETILO, ALCOXILO; n ES 0-3. SON COMPUESTOS PREFERIDOS (3'aRS,6'aSR)-1-CICLONONIL-5'-METIL-2'-FENIL-HEXAHIDRO-ESPIRO[PIPERIDIN-4,1'(2'H)-PIRROLO[3,4-c]PIRROL], (3'aRS,6'aSR)-1-CICLODECIL-5'-METIL-2'-FENIL-HEXAHIDRO-ESPIRO[PIPERIDIN-4,1'(2'H)-PIRROLO[3.4-c]PIRROL]-4',6'-DIONA, 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 EN EL TRATAMIENTO DE TRASTORNOS PSIQUIATRICOS, NEUROLOGICOS Y FISIOLOGICOS COMO TRASTORNOS DE LA ANSIEDAD, ESTRES, DEPRESION, TRAUMAS, PERDIDA DE MEMORIA DEBIDA A LA ENFERMEDAD DE ALZHEIMER, EPILEPSIA, CONVULSIONES

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：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：PE135299A1

公开(公告)日：2000-01-18

申请号：PE00117698

申请日：1998-12-03

Applicant: HOFFMANN LA ROCHE

Inventor： CESURA ANDREA ,  ADAM GEO ,  GALLEY GUIDO ,  ROVER STEPHAN ,  WICHMANN JURGEN ,  JENCK FRANCOIS

IPC: C07D235/02 ,  A61K31/00 ,  A61K31/41 ,  A61K31/435 ,  A61K31/438 ,  A61K31/44 ,  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: SE REFIERE A COMPUESTOS DE FORMULA I; R1 ES H, ALQUILO, HALOGENO, ALCOXI, TRIFLUOROMETILO, ALQUIL-FENILO, CICLOALQUILO C5-C7; R2 ES H, ALQUILO, FENILO, ALQUIL-FENILO; R3 ES H, ALQUILO, BENCILO, ALQUIL-FENILO, ALQUILDIFENILO, ENTRE OTROS; R4 ES H, ALQUILO o NITRILO; "A" ES UN CICLOALQUILO C5-C15 OPCIONALMENTE SUSTITUIDO, UN GRUPO b, c, d, ENTRE OTROS; R5 Y R6 SON H, ALQUILO O FORMAN JUNTOS UN FENILO; R7 ES H, ALQUILO; n ES 1-4. SON COMPUESTOS PREFERIDOS 8-(DECAHIDRONAFTALEN-2-IL)-1-FENIL-1,3,8-TRIAZA-ESPIRO-[4,5]-DECAN-4-ONA, 8-(CIS-OCTAHIDROINDEN-2-IL)-1-FENIL-1,3,8-TRIAZA-ESPIRO[4.5]DECAN-4-ONA, ENTRE OTROS. TAMBIEN SE REFIERE A UN PROCEDIMIENTO PARA LA PREPARACION. EL COMPUESTO I ES UN AGONISTA O ANTAGONISTA DEL RECEPTOR DE ORFANINA FQ (OFQ) POR LO QUE PUEDE SER UTIL PARA EL TRATAMIENTO DE DEFICITS DE MEMORIA Y ATENCION, TRASTORNOS PSIQUIATRICOS, NEUROLOGICOS Y PSICOLOGICOS TAL COMO TRASTORNOS DE ANSIEDAD, ESTRES, DEPRESION, TRAUMA, PERDIDA DE LA MEMORIA, ENFERMEDAD DE ALZHEIMER, EPILEPSIA, CONVULSIONES

公开(公告)号：CZ27398A3

公开(公告)日：1998-08-12

申请号：CZ27398

申请日：1998-01-29

Applicant: HOFFMANN LA ROCHE

Inventor： ADAM GEO ,  CESURA ANDREA ,  GALLEY GUIDO ,  JENCK FRANCOIS ,  MONSMA FREDERICK ,  ROVER STEPHAN ,  WICHMANN JURGEN

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: 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.