公开(公告)号：CA2299139A1

公开(公告)日：2000-08-24

申请号：CA2299139

申请日：2000-02-23

Applicant: HOFFMANN LA ROCHE

Inventor： STADLER HEINZ ,  BRANCA QUIRICO ,  GALLEY GUIDO ,  SCHNIDER PATRICK ,  BOS MICHAEL ,  HOFFMANN TORSTEN ,  HUNKELER WALTER ,  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 ,  A61P19/02 ,  A61P11/06 ,  C07D405/12 ,  C07D409/12 ,  C07D417/12 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/541

Abstract: The present invention relates to compounds of the general formula wherein ~ R is hydrogen, lower alkyl, lower alkoxy, halogen or trifluoromethyl; R1 is hydrogen or halogen; or R and R1 may be together -CH=CH-CH=CH-; R2 and R2' are independently from each other hydrogen, halogen, trifluoromethyl, lower alkoxy or cyano; or R2 and R2' may be together -CH=CH-CH=CH-, optionally substituted by one or two substituents selected from lower alkyl or lower alkoxy; R3 is hydrogen, lower alkyl or form a cycloalkyl group; R4 is hydrogen, -N(R5)2, -N(R5)(CH2)n OH, -N(R5)S(O)3-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 or the group R5 is, independently from each other, hydrogen, C3-6-cycloalkyl, benzyl or lower alkyl; R6 is hydrogen, hydroxy, lower alkyl, -(CH2)n COO-lower alkyl, -N(R5)CO-lower alkyl, hydroxy-lower alkyl, cyano, -(CH2)n O(CH2)n OH, -CHO or a 5-or 6 membered heterocyclic group, optionally bonded via an alkylene group, X is -C(O)N(R5)-, -(CH2)m O-, -(CH2)m N(R5)-, -N(R5)C(O)-, or -N(R5)(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：PE20000170A1

公开(公告)日：2000-03-29

申请号：PE00002799

申请日：1999-01-12

Applicant: HOFFMANN LA ROCHE

Inventor： BOS MICHAEL ,  RIEMER CLAUS ,  HUNKELER WALTER

IPC: C07C309/30 ,  A61K31/00 ,  A61K31/10 ,  A61K31/135 ,  A61K31/33 ,  A61K31/44 ,  A61K31/4409 ,  A61K31/4418 ,  A61K31/4427 ,  A61K31/4433 ,  A61K31/4436 ,  A61K31/505 ,  A61P25/00 ,  A61P25/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/24 ,  A61P25/28 ,  A61P43/00 ,  C07C315/04 ,  C07C317/22 ,  C07C317/32 ,  C07C317/36 ,  C07D213/61 ,  C07D213/62 ,  C07D213/71 ,  C07D213/73 ,  C07D213/74 ,  C07D213/84 ,  C07D239/38 ,  C07D317/14 ,  C07D401/04 ,  C07D401/14 ,  C07D409/04

Abstract: SE REFIERE A COMPUESTOS DE FORMULA I, DONDE R1 ES H; R2 ES H, TRIFLUOROMETILO, ALQUILO; R3 ES H o AMINO; O R1 Y R2 o R3 Y R2 SON -CH=CH-CH=CH-; Z ES PIRIMIDIN-4-ILO, PIRIDIN-4-ILO, PIRIDIN-2-ILO O FENILO; R4, R5 SON H, ALQUILO, TRIFLUOROMETILO, HALOGENO, ALCOXILO, -NH(CH2)nNR6R7, -N(CH3)(CH2)nNR6R7, NH(CH2)n-MORFOLIN-4-ILO, -NH(CH2)nOH; n ES 2-4; R6 Y R7 SON H O ALQUILO; CUANDO Z ES PIRIMIDIN-4-ILO; R4 NO ES R5; CUANDO Z ES PIRIDIN-2-ILO; R5 NO ES ALQUILO; CUANDO Z ES FENILO, R4 Y UNO DE R1-R3 NO SON H. SON COMPUESTOS PREFERIDOS [4-(4-AMINOBENCENSULFONIL)-6-BROMOPIRIMIDIN-2-IL]-METILAMINA, [2-(4-AMINOBENCENSULFONIL)-6-BROMPIRIDIN-4-IL]-METILAMINA, ENTRE OTROS. TAMBIEN SE REFIERE A UN PROCEDIMIENTO PARA LA PREPARACION. EL COMPUESTO I POSEE AFINIDAD SELECTIVA A RECEPTORES 5HT-6 POR LO QUE PUEDE SER UTIL EN EL TRATAMIENTO O PREVENCION DE TRASTORNOS DEL SISTEMA NERVIOSO CENTRAL COMO PSICOSIS, ESQUIZOFRENIA, DEPRESIONES MANIACAS, TRASTORNOS NEUROLOGICOS

公开(公告)号：ITMI20000328D0

公开(公告)日：2000-02-23

申请号：ITMI20000328

申请日：2000-02-23

Applicant: HOFFMANN LA ROCHE

Inventor： STADLER HEINZ ,  BOS MICHAEL ,  BRANCA QUIRICO ,  GALLEY GUIDO ,  HSIAO TING-HAO ,  HOFFMANN TORSTEN ,  HUNKELER WALTER ,  SCHNIDER PATRICK

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：CZ82599A3

公开(公告)日：1999-09-15

申请号：CZ82599

申请日：1999-03-10

Applicant: HOFFMANN LA ROCHE

Inventor： BOS MICHAEL ,  RIEMER CLAUS ,  STADLER HEINZ

IPC: A61K31/00 ,  A61K31/4162 ,  A61K31/505 ,  A61K31/519 ,  A61K31/529 ,  A61K31/53 ,  A61K31/535 ,  A61K31/5375 ,  A61K31/5377 ,  A61P9/10 ,  A61P25/00 ,  A61P25/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/24 ,  A61P25/28 ,  A61P43/00 ,  C07D231/54 ,  C07D251/72 ,  C07D487/04 ,  C07D495/14 ,  C07D471/04 ,  A61K31/41

Abstract: The present invention is concerned with pyrazolopyrimidines and pyrazolotriazines of the general formulae and their pharmaceutically acceptable salts. Surprisingly, these compounds have a selective affinity to 5HT-6 receptors. They are accordingly suitable for the treatment and prevention of central nervous disorders such as, for example, psychoses, schizophrenia, manic depressions, depressions, neurological disorders, memory disorders, Parkinson's disease, amyotrophic lateral sclerosis, Alzheimer's disease and Huntington's chorea.

公开(公告)号：ID21578A

公开(公告)日：1999-06-24

申请号：ID973971

申请日：1997-12-24

Applicant: HOFFMANN LA ROCHE

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

IPC: A61K31/18 ,  C07C311/30

公开(公告)号：NO944000L

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

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：NO943999D0

公开(公告)日：1994-10-21

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 ,  C07D

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：AU3991693A

公开(公告)日：1993-12-09

申请号：AU3991693

申请日：1993-05-31

Applicant: HOFFMANN LA ROCHE

Inventor： BOS MICHAEL

IPC: A61K31/495 ,  A61P25/00 ,  A61P25/18 ,  A61P25/20 ,  A61P25/24 ,  A61P25/26 ,  C07D487/04

公开(公告)号：AR062949A2

公开(公告)日：2008-12-17

申请号：ARP070104196

申请日：2007-09-24

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: Derivados de 4-fenil-piridina de formula general (1) en donde R es hidrogeno, alquilo C1-7, alcoxi C1-7, halogeno o trifluorometilo; R1 es hidrogeno o halogeno; o R y R1 pueden ser conjuntamente -CH=CH-CH=CH-; R2 y R2' son independientemente, hidrogeno, halogeno, trifluorometilo, ciano o alcoxi C1-7; o R2 y R2' pueden ser conjuntamente -CH=CH-CH=CH-, sustituido opcionalmente por uno o dos sustituyentes seleccionados de alquilo C1-7 o de alcoxi C1-7;.R3 es hidrogeno, alquilo C1-7 o forma un grupo cicloalquilo C3-6; R4 es hidrogeno, -N(R5)2, -N(R5)(CH2)nOH, -N(R5)S(O)2-alquilo C1-7, -N(R5)S(O)2-fenilo, -N=CH-N(R5)2, -N(R5)C(O)R5 o una amina terciaria cíclica del grupo de formula (2) o (3) en donde la amina terciaria cíclica se selecciona del grupo constituido por pirrol-1-ilo, imidazol-1-ilo, piperidin-1-ilo, piperazin-1-ilo, morfolin-4-ilo, tiomorfolin-4-ilo, 1-oxo-tiomorfolin-4-ilo o 1,1-dioxo-tiomorfolin-4-ilo; R5 es independientemente, hidrogeno, cicloalquilo C3-6, bencilo o alquilo C1-7; R6 es hidrogeno, hidroxi, alquilo C1-7, -(CH2)nCOO-alquilo C1-7, ciano, -(CH2)n O(CH2)nOH, -CHO o un grupo heterocíclico de 5 o 6 miembros, seleccionado del grupo constituido por piridinilo, pirimidinilo, oxadiazolilo, triazolilo, tetrazolilo, tiazolilo, tienilo, furilo, piranilo, pirrolilo, imidazolilo, pirazolilo, isotiazolilo, piperazinilo o piperidilo, unido opcionalmente por un grupo alquileno, X es -C(O)N(R5)-, n es 0-4; y m es 1 o 2; y sales de adicion ácida farmacéuticamente aceptables de los mismos

公开(公告)号：CA2253547C

公开(公告)日：2006-10-17

申请号：CA2253547

申请日：1997-04-24

Applicant: HOFFMANN LA ROCHE

Inventor： BOS MICHAEL ,  STADLER HEINZ ,  WICHMANN JURGEN

IPC: C07D307/85 ,  A61K31/34 ,  A61K31/343 ,  A61P25/00 ,  A61P25/20 ,  A61P25/28 ,  C07D307/86

Abstract: The invention is concerned with the use of compounds of general formula (I) wherein R1-R4 signify hydrogen, halogen, lower-alkyl, lower-alkoxy, aryl, benzyloxy, lower-alkoxy-lower-alkyl, lower-alkyl- sulphanyl, lower-alkyl-sulphanyl-lower-alkyl or R1 and R2 together signify the group -O-(CH2)2- or -(CH2)2-O- and R5 signifies hydrogen or hydroxy, as well as their pharmaceutically acceptable salts in the control or prevention of illnesses or disorders of the central nervous system such as migraine, schizophrenia, anxiety states, sleep disorders, anorexia, Alzheimer's disease, addictions (alcohol, nicotine, benzodi- azepine, cocaine, etc.), as well as disorders which result from damage to the head/brain or to the spinal column/bone marrow and, respectively, for the production of corresponding medicaments.