公开(公告)号：FR2790473A1

公开(公告)日：2000-09-08

申请号：FR0002170

申请日：2000-02-22

Applicant: HOFFMANN LA ROCHE

Inventor： BOS MICHAEL ,  BRANCA QUIRICO ,  GALLEY GUIDO ,  GODEL THIERRY ,  HOFFMANN TORSTEN ,  HUNKELER WALTER ,  SCHNIDER PATRICK ,  STADLER HEINZ

IPC: A61K20060101 ,  A61K31/44 ,  A61K31/4409 ,  A61K31/4418 ,  A61K31/4427 ,  A61K31/444 ,  A61K31/455 ,  A61K31/496 ,  A61P1/00 ,  A61P9/00 ,  A61P11/00 ,  A61P25/00 ,  A61P25/04 ,  A61P25/28 ,  A61P25/30 ,  A61P27/02 ,  A61P29/00 ,  A61P43/00 ,  C07D20060101 ,  C07D213/30 ,  C07D213/38 ,  C07D213/40 ,  C07D213/63 ,  C07D213/65 ,  C07D213/74 ,  C07D213/75 ,  C07D213/78 ,  C07D213/82 ,  C07D401/04 ,  C07D401/12 ,  C07D413/12 ,  C07D413/14 ,  A61K31/4545

Abstract: The present invention relates to compounds of the general formula wherein R is hydrogen, lower alkyl, lower alkoxy, halogen or trifluoromethyl; R is hydrogen or halogen; or R and R may be together -CH=CH-CH=CH-; R and R are independently from each other hydrogen, halogen, trifluoromethyl, lower alkoxy or cyano; or R and R may be together -CH=CH-CH=CH-, optionally substituted by one or two substituents selected from lower alkyl or lower alkoxy; R is hydrogen, lower alkyl or form a cycloalkyl group; R is hydrogen, -N(R )2, -N(R )(CH2)nOH, -N(R )S(O)2-lower alkyl, -N(R )S(O)2-phenyl, -N=CH-N(R )2, -N(R )C(O)R or a cyclic tertiary amine of the group R is, independently from each other, hydrogen, C3-6-cycloalkyl, benzyl or lower alkyl; R is hydrogen, hydroxy, lower alkyl, -(CH2)nCOO-lower alkyl, -N(R )CO-lower alkyl, hydroxy-lower alkyl, cyano, -(CH2)nO(CH2)nOH, -CHO or a 5-or 6 membered heterocyclic group, optionally bonded via an alkylene group, X is -C(O)N(R )-, -(CH2)mO-, -(CH2)mN(R )-, -N(R )C(O)-, or -N(R )(CH2)m-; n is 0 - 4; and m is 1 or 2; and to pharmaceutically acceptable acid addition salts thereof. The compounds of formula I show a high affinity to the NK-1 receptor. They may be used for the treatment of diseases, which relate to NK-1 receptor antagonists.

公开(公告)号：PE44199A1

公开(公告)日：1999-05-06

申请号：PE00000598

申请日：1998-01-05

Applicant: HOFFMANN LA ROCHE

Inventor： STADLER HEINZ ,  BOS MICHAEL ,  WICHMANN JURGEN

IPC: C07D217/24 ,  C07D221/10 ,  A61K31/40 ,  A61K31/403 ,  A61K31/435 ,  A61K31/473 ,  A61P1/00 ,  A61P7/02 ,  A61P9/00 ,  A61P9/12 ,  A61P25/00 ,  C07D209/62

Abstract: SE REFIEREN A COMPUESTOS DE FORMULA (I), EN DONDE: R1, R2, R3 Y R4 SON H, HALOGENO, OH, ALQUILO INFERIOR, ALCOXILO INFERIOR o FENILO; o R2 Y R3 JUNTOS SON -O-CH2-O-; R5 ES H, ALQUILO INFERIOR o BENCILO; n ES 0 o 1; CON LA CONDICION DE QUE EL COMPUESTO (I) NO ES 2-METIL-1,3,4,4a,5,10b-HEXAHIDRO-2H-BENZO[H]ISOQUINOLIN-6-ONA RACEMICA. TAMBIEN SE REFIERE A SU PROCEDIMIENTO DE PREPARACION. LOS COMPUESTOS DE FORMULA (I) ACTUAN UNIENDOSE A LOS RECEPTORES (5HT2) DE SEROTONINA, SIENDO UTILES EN EL TRATAMIENTO O PREVENCION DE TRASTORNOS DEL SISTEMA NERVIOSO CENTRAL TALES COMO DEPRESION, ANSIEDAD, INSOMNIO, PSICOSIS, ENTRE OTROS

公开(公告)号：MX9704817A

公开(公告)日：1997-12-31

申请号：MX9704817

申请日：1997-06-26

Applicant: HOFFMANN LA ROCHE

Inventor： BOS MICHAEL ,  GODEL THIERRY ,  RIEMER CLAUS ,  SLEIGHT ANDREW

IPC: A61K31/63 ,  A61K31/18 ,  A61K31/325 ,  A61K31/40 ,  A61K31/403 ,  A61K31/404 ,  A61K31/44 ,  A61K31/505 ,  A61P25/00 ,  C07C311/21 ,  C07C311/38 ,  C07C311/44 ,  C07D209/08 ,  C07D213/76 ,  C07D239/48 ,  C07D239/50 ,  C07D239/69 ,  C07D403/04 ,  C07C317/32 ,  C07D247/00

Abstract: El presente invento se refiere a compuestos de formula general I en donde (Ver Formula) Z significa un grupo de fenilo sustituido, piridilo sustituido o indolilo sustituido de las formulas a-e (Ver Formula) R1 significa hidrogeno, amino, alquilamino inferior, dialquilamino inferior, alquilo inferior, halogeno o trifluorometilo; R2 significa hidrogeno o alquilo inferior; R3 significa hidrogeno, amino, alquilamino inferior, dialquilamino inferior, alquilo inferior, CF3, alcoxilo inferior o halogeno; R4 significa amino, alquilamino inferior, dialquilamino inferior, alquilo inferior, alcoxilo inferior o halogeno; R5 significa hidrogeno, alquilamino inferior, di-alquilamino inferior, alcoxilo inferior o halogeno; R6 significa alquilo inferior, alquilamino inferior, di-alquilamino inferior, alcoxilo inferior, halogeno o CF3, R7 significa amino, alquilamino inferior, di-alquilamino inferior, alcoxilo inferior, alquilsulfanilo inferior, mercapto, pirrolidin-1-ilo o azetidin-1-ilo; R8 significa amino, alquilamino inferior, di-alquilamino inferior, bencilamino, alcoxilo inferior, alquilsulfanilo inferior, halogeno, pirrolidin-1-ilo o azetidin-1-ilo; R9 y R10 significan cada uno, independientemente, alcoxilo inferior o alquilamino inferior; R11 significa hidrogeno o halogeno; R12 significa hidrogeno o alquilo inferior, y a significa un doble enlace opcional, con la salvedad de que R7 y R8 no significan simultáneamente metoxilo, así como sus sales farmacéuticamente aceptables, como sustancias terapéuticamente activs contra trastornos del sistema nervioso central y para la produccion de medicamentos correspondientes.

公开(公告)号：NZ264711A

公开(公告)日：1996-07-26

申请号：NZ26471194

申请日：1994-10-17

Applicant: HOFFMANN LA ROCHE

Inventor： BOS MICHAEL ,  WICHMANN JURGEN ,  WIDMER ULRICH

IPC: C07D491/052 ,  A61K31/40 ,  A61K31/403 ,  A61P1/00 ,  A61P7/02 ,  A61P9/12 ,  A61P25/00 ,  A61P25/04 ,  A61P25/06 ,  A61P25/18 ,  A61P25/20 ,  A61P25/24 ,  A61P25/26 ,  A61P25/28 ,  C07D209/56 ,  C07D209/58 ,  C07D209/60 ,  C07D209/70 ,  C07D209/96 ,  C07D491/04 ,  C07D495/04 ,  C07D513/04

Abstract: The present invention relates to tricyclic pyrrole derivatives of the formula wherein R to R are each hydrogen, halogen, lower alkyl, phenyl, cycloalkyl or lower alkoxy and R is additionally lower alkoxycarbonyl, acyloxy or mesyloxy; R to R are each hydrogen or lower alkyl; X is -CH2CH(C6H5)-, -CH=C(C6H5)-, -YCH2-, -CH=CH- or -(CR )n; R and R are each hydrogen, phenyl, lower alkyl or halogen; n is 1 to 3 and Y is O or S, and pharmaceutically acceptable salts of basic compounds of the formula I with acids. These compounds are particularly suitable for the control or prevention of central nervous disorders, such as depressions, bipolar disorders, anxiety states, sleep and sexual disorders, psychoses, schizophrenia, migraine and other states associated with headache or pain of other types, personality disorders or obsessive-compulsive disorders, social phobias or panic attacks, organic mental disorders, mental disorders in childhood, aggressiveness, age-related memory disorders and behavioural disorders, addiction, obesity, bulimia etc.; damage to the nervous system as a result of trauma, stroke, neurodegenerative disorders etc.; cardiovascular disorders, such as high blood pressure, thrombosis, stroke etc.; and gastrointestinal disorders, such as dysfunction of the motility of the gastrointestinal tract.

公开(公告)号：CZ260394A3

公开(公告)日：1995-07-12

申请号：CZ260394

申请日：1994-10-21

Applicant: HOFFMANN LA ROCHE

Inventor： BOS MICHAEL ,  WICHMANN JURGEN ,  WIDMER ULRICH

IPC: C07D491/052 ,  A61K31/40 ,  A61K31/403 ,  A61P1/00 ,  A61P7/02 ,  A61P9/12 ,  A61P25/00 ,  A61P25/04 ,  A61P25/06 ,  A61P25/18 ,  A61P25/20 ,  A61P25/24 ,  A61P25/26 ,  A61P25/28 ,  C07D209/56 ,  C07D209/58 ,  C07D209/60 ,  C07D209/70 ,  C07D209/96 ,  C07D491/04 ,  C07D495/04 ,  C07D513/04

Abstract: The present invention relates to tricyclic pyrrole derivatives of the formula wherein R to R are each hydrogen, halogen, lower alkyl, phenyl, cycloalkyl or lower alkoxy and R is additionally lower alkoxycarbonyl, acyloxy or mesyloxy; R to R are each hydrogen or lower alkyl; X is -CH2CH(C6H5)-, -CH=C(C6H5)-, -YCH2-, -CH=CH- or -(CR )n; R and R are each hydrogen, phenyl, lower alkyl or halogen; n is 1 to 3 and Y is O or S, and pharmaceutically acceptable salts of basic compounds of the formula I with acids. These compounds are particularly suitable for the control or prevention of central nervous disorders, such as depressions, bipolar disorders, anxiety states, sleep and sexual disorders, psychoses, schizophrenia, migraine and other states associated with headache or pain of other types, personality disorders or obsessive-compulsive disorders, social phobias or panic attacks, organic mental disorders, mental disorders in childhood, aggressiveness, age-related memory disorders and behavioural disorders, addiction, obesity, bulimia etc.; damage to the nervous system as a result of trauma, stroke, neurodegenerative disorders etc.; cardiovascular disorders, such as high blood pressure, thrombosis, stroke etc.; and gastrointestinal disorders, such as dysfunction of the motility of the gastrointestinal tract.

公开(公告)号：NO944000A

公开(公告)日：1995-04-24

申请号：NO944000

申请日：1994-10-21

Applicant: HOFFMANN LA ROCHE

Inventor： BOS MICHAEL ,  WICHMANN JURGEN ,  WIDMER ULRICH

IPC: C07D491/052 ,  A61K31/40 ,  A61K31/403 ,  A61P1/00 ,  A61P7/02 ,  A61P9/12 ,  A61P25/00 ,  A61P25/04 ,  A61P25/06 ,  A61P25/18 ,  A61P25/20 ,  A61P25/24 ,  A61P25/26 ,  A61P25/28 ,  C07D209/56 ,  C07D209/58 ,  C07D209/60 ,  C07D209/70 ,  C07D209/96 ,  C07D491/04 ,  C07D495/04 ,  C07D513/04

CPC classification number: C07D209/96 ,  C07D209/60 ,  C07D209/70 ,  C07D491/04

公开(公告)号：NO943999L

公开(公告)日：1995-04-24

申请号：NO943999

申请日：1994-10-21

Applicant: HOFFMANN LA ROCHE

Inventor： BOS MICHAEL

IPC: A61K31/40 ,  A61K31/403 ,  A61K31/404 ,  A61K31/4045 ,  A61P1/00 ,  A61P7/02 ,  A61P9/00 ,  A61P9/12 ,  A61P25/00 ,  A61P25/06 ,  A61P25/18 ,  A61P25/20 ,  A61P25/24 ,  A61P25/26 ,  A61P25/28 ,  A61P43/00 ,  C07D209/04 ,  C07D209/08 ,  C07D209/24 ,  C07D209/30 ,  C07D209/36

Abstract: The invention relates to compounds of the formula wherein R to R are hydrogen, halogen, lower alkyl, cycloalkyl or trifluoromethyl, R and R are hydrogen, halogen, lower alkyl, cycloalkyl, trifluoromethyl, hydroxyl or lower alkoxy and R is hydrogen or lower alkyl, and pharmaceutically acceptable acid addition salts of the compounds of the formula I. These compounds are particularly suitable for the treatment or prevention of central nervous disorders such as depressions, bipolar disorders, anxiety states, sleep and sexual disorders, psychoses, schizophrenia, migraine and other conditions associated with headache or pain of other types, personality disorders or obsessive-compulsive disorders, social phobia or panic attacks, organic mental disorders, mental disorders in childhood, aggressiveness, age-related memory disorders and behavioural disorders, addiction, obesity, bulimia etc., damage to the central nervous system as a result of trauma, stroke, neurodegenerative disorders etc.; cardiovascular disorders, such as high blood pressure, thrombosis, stroke, and gastrointestinal disorders, such as dysfunction of the motility of the gastrointestinal tract.

公开(公告)号：NO943999A

公开(公告)日：1995-04-24

申请号：NO943999

申请日：1994-10-21

Applicant: HOFFMANN LA ROCHE

Inventor： BOS MICHAEL

IPC: A61K31/40 ,  A61K31/403 ,  A61K31/404 ,  A61K31/4045 ,  A61P1/00 ,  A61P7/02 ,  A61P9/00 ,  A61P9/12 ,  A61P25/00 ,  A61P25/06 ,  A61P25/18 ,  A61P25/20 ,  A61P25/24 ,  A61P25/26 ,  A61P25/28 ,  A61P43/00 ,  C07D209/04 ,  C07D209/08 ,  C07D209/24 ,  C07D209/30 ,  C07D209/36

CPC classification number: C07D209/36 ,  C07D209/08

公开(公告)号：SE1035115T5

公开(公告)日：2015-08-04

申请号：SE00102260

申请日：2000-02-15

Applicant: HOFFMANN LA ROCHE

Inventor： SCHNIDER PATRICK ,  HOFFMANN MATTHIAS ,  HUNKELER WALTER ,  STADLER HEINZ ,  GALLEY GUIDO ,  BOS MICHAEL ,  BRANCA QUIRICO ,  GODEL THIERRY

IPC: A61K20060101 ,  A61K31/44 ,  A61K31/4409 ,  A61K31/4418 ,  A61K31/4427 ,  A61K31/444 ,  A61K31/455 ,  A61K31/496 ,  A61P1/00 ,  A61P9/00 ,  A61P11/00 ,  A61P25/00 ,  A61P25/04 ,  A61P25/28 ,  A61P25/30 ,  A61P27/02 ,  A61P29/00 ,  A61P43/00 ,  C07D20060101 ,  C07D213/30 ,  C07D213/38 ,  C07D213/40 ,  C07D213/63 ,  C07D213/65 ,  C07D213/74 ,  C07D213/75 ,  C07D213/78 ,  C07D213/82 ,  C07D401/04 ,  C07D401/12 ,  C07D413/12 ,  C07D413/14

Abstract: The present invention relates to compounds of the general formula wherein R is hydrogen, lower alkyl, lower alkoxy, halogen or trifluoromethyl; R is hydrogen or halogen; or R and R may be together -CH=CH-CH=CH-; R and R are independently from each other hydrogen, halogen, trifluoromethyl, lower alkoxy or cyano; or R and R may be together -CH=CH-CH=CH-, optionally substituted by one or two substituents selected from lower alkyl or lower alkoxy; R is hydrogen, lower alkyl or form a cycloalkyl group; R is hydrogen, -N(R )2, -N(R )(CH2)nOH, -N(R )S(O)2-lower alkyl, -N(R )S(O)2-phenyl, -N=CH-N(R )2, -N(R )C(O)R or a cyclic tertiary amine of the group R is, independently from each other, hydrogen, C3-6-cycloalkyl, benzyl or lower alkyl; R is hydrogen, hydroxy, lower alkyl, -(CH2)nCOO-lower alkyl, -N(R )CO-lower alkyl, hydroxy-lower alkyl, cyano, -(CH2)nO(CH2)nOH, -CHO or a 5-or 6 membered heterocyclic group, optionally bonded via an alkylene group, X is -C(O)N(R )-, -(CH2)mO-, -(CH2)mN(R )-, -N(R )C(O)-, or -N(R )(CH2)m-; n is 0 - 4; and m is 1 or 2; and to pharmaceutically acceptable acid addition salts thereof. The compounds of formula I show a high affinity to the NK-1 receptor. They may be used for the treatment of diseases, which relate to NK-1 receptor antagonists.

公开(公告)号：MY147451A

公开(公告)日：2012-12-14

申请号：MYPI20044751

申请日：2000-02-22

Applicant: HOFFMANN LA ROCHE

Inventor： BOS MICHAEL ,  BRANCA QUIRICO ,  GALLEY GUIDO ,  GODEL THIERRY ,  HOFFMANN TORSTEN ,  HUNKELER WALTER ,  SCHNIDER PATRICK ,  STADLER HEINZ

IPC: C07D213/82 ,  A61K20060101 ,  A61K31/44 ,  A61K31/4409 ,  A61K31/4418 ,  A61K31/4427 ,  A61K31/444 ,  A61K31/455 ,  A61K31/496 ,  A61P1/00 ,  A61P9/00 ,  A61P11/00 ,  A61P25/00 ,  A61P25/04 ,  A61P25/28 ,  A61P25/30 ,  A61P27/02 ,  A61P29/00 ,  A61P43/00 ,  C07D20060101 ,  C07D213/30 ,  C07D213/38 ,  C07D213/40 ,  C07D213/63 ,  C07D213/65 ,  C07D213/74 ,  C07D213/75 ,  C07D213/78 ,  C07D401/04 ,  C07D401/12 ,  C07D413/12 ,  C07D413/14

Abstract: THE PRESENT INVENTION RELATES TO COMPOUNDS OF THE GENERAL FORMULAWHEREINRIS HYDROGEN, LOWER ALKYL, LOWER ALKOXY, HALOGEN OR TRIFLUOROMETHYL;R1IS HYDROGEN OR HALOGEN; ORR AND R1 MAY BE TOGETHER -CH=CH-CH=CH-;R2 AND R2' ARE INDEPENDENTLY FROM EACH OTHER HYDROGEN, HALOGEN, TRIFLUOROMETHYL, LOWER ALKOXY OR CYANO; ORR2 AND R2' MAY BE TOGETHER -CH=CH-CH=CH-, OPTIONALLY SUBSTITUTED BY ONE OR TWO SUBSTITUENTS SELECTED FROM LOWER ALKYL OR LOWER ALKOXYR3IS HYDROGEN, LOWER ALKYL OR FORM A CYCLALKYL GROUP;R4IS HYDROGEN, -N(R5)2, -N(R5)(CH2)nOH, -N(R5)S(O)2-LOWER ALKYL, -N(R5)S(O)2- PHENYL, -N=CH-N(R5)2, -N(R5)C(O)R5 OR A CYCLIC TERTIARY AMINE OF THE GROUP R5IS, INDEPENDENTLY FROM EACH OTHER, HYDROGEN, C3-6CYCLOALKYL, BENZYL OR LOWER ALKYL;R6IS HYDROGEN, HYDROXY, LOWER ALKYL, -(CH2)nCOO-LOWER ALKYL, -N(R5)CO-LOWER ALKYL, HYDROXY-LOWER ALKYL, CYANO, -(CH2)nO(CH2)nOH, -CHO OR A 5-OR 6 MEMBERED HETEROCYCLIC GROUP, OPTIONALLY BONDED VIA AN ALKYLENE GROUP, XIS -C(O)N(R5)-, -(CH2)mO-, -(CH2)mN(R5)-, -N(R5)C(O)-, OR -N(R5)(CH2)m-;nIS 0-4;mIS 1 OR 2;AND TO PHARMACEUTICALLY ACCEPTABLE ACID ADDITION SALTS THEREOF. THE COMPOUNDS OF FORMULA 1 SHOW A HIGH AFFINITY TO THE NK-1 RECEPTOR. THEY MAY USED FOR THE TREATMENT OF DISEASES, WHICH RELATE TO NK-1 RECEPTOR ANTAGONISTS.@