公开(公告)号：HRP980043B1

公开(公告)日：2001-12-31

申请号：HRP980043

申请日：1998-01-27

Applicant: HOFFMANN LA ROCHE

Inventor： GEO ADAM ,  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 ,  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：GR3036523T3

公开(公告)日：2001-12-31

申请号：GR20010401383

申请日：2001-09-05

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 ,  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：DE69800896D1

公开(公告)日：2001-07-19

申请号：DE69800896

申请日：1998-01-21

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 ,  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：BR9913106A

公开(公告)日：2001-05-08

申请号：BR9913106

申请日：1999-09-02

Applicant: HOFFMANN LA ROCHE

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

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.

公开(公告)号：TR199901380A2

公开(公告)日：2001-01-22

申请号：TR9901380

申请日：1999-06-11

Applicant: HOFFMANN LA ROCHE

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

IPC: A61K20060101 ,  C07D401/04 ,  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 ,  C07D

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：PE10282000A1

公开(公告)日：2000-10-12

申请号：PE00088699

申请日：1999-09-02

Applicant: HOFFMANN LA ROCHE

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

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

CPC classification number: C07D211/20 ,  C07D211/42

Abstract: SE REFIERE A COMPUESTOS DE PIPERIDINA DE FORMULA I, DONDE R1 ES TETRAHIDRONAFTILO, (CH2)nC6H5R4; n ES 0-4; R4 ES H, ALQUILO, ALCOXILO, CICLOALQUILO C5-C12 OPCIONALMENTE SUSTITUIDO POR ALQUILO; R2 ES H, OH, ALCOXILO, ALQUENILOXILO, ALQUILO; R3 ES CICLOALQUILO C5-C7, FENILO OPCIONALMENTE SUSTITUIDO CON OH, HALOGENO, ALCOXILO, ALQUENILOXILO, ALQUILO, O-(CH2)n-C6H5; n ES 0-3. SON COMPUESTOS PREFERIDOS (3RS,4RS)-1-CICLONONIL-4-(2-HIDROXI-FENIL)PIPERIDIN-3-OL; 1-CICLODECIL-4-(2-METOXI-FENIL)-PIPERIDINA, (3RS,4RS)-1-CICLODECIL-4-(2-ISOPROPIL-FENIL)PIPERIDIN-3-OL), 2-(1-CICLODECIL-PIPERIDIN-4-IL)FENOL, ENTRE OTROS. TAMBIEN SE REFIERE A UN PROCEDIMIENTO PARA LA PREPARACION. EL COMPUESTO I ES UN AGONISTA-ANTAGONISTA DEL RECEPTOR ORFANINA FQ (OFQ), POR LO QUE PUEDE SER UTIL PARA TRATAMIENTO DE DEFICITS DE MEMORIA, ATENCION, TRASTORNOS PSIQUIATRICOS, NEUROLOGICOS, FISIOLOGICOS

公开(公告)号：PE05482000A1

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

CPC classification number: 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：HU9802807A2

公开(公告)日：1999-08-30

申请号：HU9802807

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 ,  A61K31/445

Abstract: The present invention relates to compounds of formula I and pharmaceutically acceptable acid addition salts thereof.

公开(公告)号：AU2157899A

公开(公告)日：1999-06-28

申请号：AU2157899

申请日：1998-12-03

Applicant: HOFFMANN LA ROCHE

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

IPC: A61K31/435 ,  A61K31/438 ,  A61K31/439 ,  A61P25/00 ,  A61P25/04 ,  A61P25/08 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/30 ,  C07D221/20 ,  C07D451/04 ,  C07D471/10 ,  C07D491/10 ,  C07D491/107 ,  C07D491/20 ,  C07D498/10 ,  C07D498/20 ,  A61K31/44 ,  C07D471/20

Abstract: The present invention relates to compounds of the formula wherein X is -O- or -CH2-; Y is -C(O)-, -(CH2)n- or -N(CH3)-; n is 1 or 2 or X and Y taken together are -CH=CH-Z is -NH-, -CH2-, -O- or =CH-; A1 is a group B is -(CH2)m-; m is 0, 1 or 2; R1 and R2 are each independently hydrogen or lower alkyl; R3 is hydrogen or halogen; R4 is hydrogen or hydroxy and the dotted line is (-CH2-CH2-)n, and n' is 0 or 1 and to pharmaceutically acceptable acid addition salts thereof. The compounds of the present invention are antagonists of the OFQ receptor. Consequently they will be useful in the treatment of memory and attention deficits, psychiatric, neurological and physiological disorders, especially, but not limited to, amelioration of symptoms of anxiety and stress disorders, depression, memory loss due to Alzheimer's disease or other dementias, epilepsy and convulsions, acute and/or chronic pain conditions, symptoms of addictive drug withdrawal, control of water balance, Na+ excretion and arterial blood pressure disorders and metabolic disorders such as obesity.

公开(公告)号：AU9608798A

公开(公告)日：1999-06-24

申请号：AU9608798

申请日：1998-12-04

Applicant: HOFFMANN LA ROCHE

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

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 ,  A61K31/535

Abstract: The present invention relates to compounds of formula I and pharmaceutically acceptable acid addition salts thereof.