公开(公告)号：BRPI0513379A

公开(公告)日：2008-05-06

申请号：BRPI0513379

申请日：2005-07-06

Applicant: HOFFMANN LA ROCHE

Inventor： GALLEY GUIDO ,  JAKOB-ROETNE ROLAND ,  KITAS ERIC ARGIRIOS

IPC: C07D223/08 ,  A61K31/55 ,  A61P25/28 ,  A61P35/00

Abstract: The invention relates to compounds of the general formula in which R 1 , R 2 , R3, R 4 , R 2' , R3', R 4' , R 5 , and X is -CHR- are as defined in the specification. The invention also provides pharmaceutically acceptable acid addition salts, optically pure enantiomers, racemates and diastereomeric mixtures of such compounds. The invention further provides methods for the treatment of Alzheimer's disease or common cancers.

公开(公告)号：CA2666762A1

公开(公告)日：2008-04-24

申请号：CA2666762

申请日：2007-10-09

Applicant: HOFFMANN LA ROCHE

Inventor： GOERGLER ANNICK ,  GROEBKE ZBINDEN KATRIN ,  NORCROSS ROGER ,  STALDER HENRI ,  GALLEY GUIDO

IPC: C07D233/64 ,  A61K31/4178 ,  A61P25/00

Abstract: The present invention relates to compounds of formula (I) wherein R1 is h ydrogen, lower alkyl, -(CR2)n-OH, -(CH2)n-aryl or -(CH2)n-heteroaryl, which are optionally substituted by halogen, lower alkoxy or lower alkyl substitut ed by halogen, or is -(CR2)n- cycloalkyl, optionally substituted by hydroxy, -(CH2)n-heterocyclyl, -(CH2)n-NH-S(O)2CH3, or is -(CR2)nO-lower alkyl or lo wer alkyl substituted by halogen; R is hydrogen or lower alkyl, and when two R-groups are present, they may or may not be the same; R2 is 2,2-dioxo-2,3- dihydro-1H-benzo[c]thiophenyl, 6,7-dihydro-5H-cyclopentapyrimidin-2-yl, 2,2- difluoro-benzo[1,3]dioxol-5-yl, 2,2,3,3-tetrafluoro-2,3-dihydro-benzo[1,4]di oxin-6-yl, or is aryl or heteroaryl, optionally substituted by one or more s ubstituents, selected from the group consisting of halogen, lower alkyl, cyc loalkyl, -(CH2)n-hydroxy, lower alkyl substituted by halogen, lower alkoxy s ubstituted by halogen, -S(O)2-lower alkyl, -(CH2)n-S(O)2-NH-lower alkyl, -(C H2)n-O-lower alkyl, nitro, amino, cyano, -NHC(O)-lower alkyl, -C(O)NH-lower alkyl, or O-tetrahydro-naphthalenyl, or are substituted by -(CH2)n-aryl, opt ionally substituted by halogen, or by -CH=CH-aryl, optionally substituted by halogen, or by -(CH2)n-O-aryl, optionally substituted by halogen, lower alk oxy or lower alkyl substituted by halogen, or by -O-(CH2)n-aryl, optionally substituted by halogen, or by -(CH2)n-heteroaryl, or by -(CH2)n-O-heteroaryl or by -(CH2)n-heterocyclyl, optionally substituted by =O, or by -(CH2)n-O-h eterocyclyl, optionally substituted by lower alkyl, or by -S-aryl, -CH(OH)-a ryl, -C(CH3)2-aryl, -NR-aryl, or by 2-oxo-2H-pyridin-1-yl; R3 is hydrogen or lower alkyl; R4 is hydrogen or lower alkyl; n is 0, 1, 2, 3 or 4 and to the ir pharmaceutically active salts for the treatment of depression, anxiety di sorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders such as schizophrenia, neurolo gical diseases such as Parkinson's disease, neurodegenerative disorders such as Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse a nd metabolic disorders such as eating disorders, diabetes, diabetic complica tions, obesity, dyslipidemia, disorders of energy consumption and assimilati on, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders.

公开(公告)号：AU2007312390A1

公开(公告)日：2008-04-24

申请号：AU2007312390

申请日：2007-10-09

Applicant: HOFFMANN LA ROCHE

Inventor： NORCROSS ROGER ,  STALDER HENRI ,  GALLEY GUIDO ,  ZBINDEN KATRIN GROEBKE ,  GOERGLER ANNICK

IPC: C07D233/64 ,  A61K31/4178 ,  A61P25/00

Abstract: The present invention relates to amino-4-methyl imidazoles and pharmaceutically-acceptable salts thereof. The compound may be used for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders such as schizophrenia, neurological diseases such as Parkinson's disease, neurodegenerative disorders such as Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse and metabolic disorders such as eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders.

公开(公告)号：AU2007312389A1

公开(公告)日：2008-04-24

申请号：AU2007312389

申请日：2007-10-09

Applicant: HOFFMANN LA ROCHE

Inventor： NORCROSS ROGER ,  GOERGLER ANNICK ,  ZBINDEN KATRIN GROEBKE ,  GALLEY GUIDO ,  STALDER HENRI

IPC: C07D233/64 ,  A61K31/417 ,  A61P25/00 ,  C07D401/12 ,  C07D403/12 ,  C07D409/12

Abstract: The present invention relates to compounds of formula I wherein R 1 is selected from the group consisting of hydrogen or lower alkyl; R 2 is hydrogen, lower alkyl, lower alkenyl, lower alkyl substituted by hydroxy, lower alkyl substituted by halogen, -(CH 2 ) x -S-lower alkyl, -(CH 2 ) x -O-lower alkyl, -(CH 2 ) x -NHC(O)O-lower alkyl, -(CH 2 ) x -aryl, and -(CH 2 ) x -heteroaryl; each R 3 is selected from the group consisting of hydrogen, lower alkyl, lower alkoxy, halogen, hydroxy, lower alkyl substituted by halogen, -O-(CH 2 ) m -aryl, -O-(CH 2 ) m -heteroaryl, -(CR 2 ) m -aryl, and -(CR 2 ) m -heteroaryl; each R is selected from the group consisting of hydrogen, lower alkyl and hydroxy; Ar is selected from the group consisting of phenyl, pyrimidin-2-yl, pyrimidin-4-yl and pyridin-3-yl; n is 0, 1 or 2; x is 0, 1, 2 or 3; m is 0 or 1; and to their pharmaceutically active salts.

公开(公告)号：CA2637312A1

公开(公告)日：2007-08-02

申请号：CA2637312

申请日：2007-01-17

Applicant: HOFFMANN LA ROCHE

Inventor： GROEBKE ZBINDEN KATRIN ,  GALLEY GUIDO ,  NORCROSS ROGER ,  KOLCZEWSKI SABINE ,  HOENER MARIUS ,  STALDER HENRI

IPC: A61K31/4164 ,  A61K31/4174 ,  A61P25/00 ,  C07D233/06 ,  C07D233/54 ,  C07D401/04 ,  C07D405/06 ,  C07D409/06

Abstract: The present invention relates a method for treating depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder, stress-related disorders, psychotic disorders such as schizophrenia, neurological diseases such as Parkinson's disease, neurodegenerative disorders such as Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse and metabolic disorders such as eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders which comprises administering to an individual a therapeutically effective amount of a compound of formula I wherein R, R1, R2, A and n are as defined in the specification and to their pharmaceutically active salts. The invention also relates to novel compounds of formula I, pharmaceutical compositions containing them, and methods for their preparation.

公开(公告)号：AU2007209381A1

公开(公告)日：2007-08-02

申请号：AU2007209381

申请日：2007-01-17

Applicant: HOFFMANN LA ROCHE

Inventor： ZBINDEN KATRIN GROEBKE ,  HOENER MARIUS ,  NORCROSS ROGER ,  STALDER HENRI ,  GALLEY GUIDO ,  KOLCZEWSKI SABINE

IPC: A61K31/4164 ,  A61K31/4174 ,  A61P25/00 ,  C07D233/06 ,  C07D233/54 ,  C07D401/04 ,  C07D405/06 ,  C07D409/06

Abstract: The present invention relates a method for treating depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder, stress-related disorders, psychotic disorders such as schizophrenia, neurological diseases such as Parkinson's disease, neurodegenerative disorders such as Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse and metabolic disorders such as eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders which comprises administering to an individual a therapeutically effective amount of a compound of formula I wherein R, R1, R2, A and n are as defined in the specification and to their pharmaceutically active salts. The invention also relates to novel compounds of formula I, pharmaceutical compositions containing them, and methods for their preparation.

公开(公告)号：GC0000338A

公开(公告)日：2007-03-31

申请号：GCP2000685

申请日：2000-05-30

Applicant: HOFFMANN LA ROCHE

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

IPC: A61K31/00 ,  A61K31/505 ,  A61K31/506 ,  A61K31/513 ,  A61K31/5377 ,  A61P1/04 ,  A61P1/08 ,  A61P9/00 ,  A61P11/02 ,  A61P11/06 ,  A61P17/02 ,  A61P25/00 ,  A61P25/06 ,  A61P25/16 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/30 ,  A61P29/00 ,  A61P37/08 ,  A61P43/00 ,  C07D213/00 ,  C07D239/00 ,  C07D239/28 ,  C07D239/34 ,  C07D239/38 ,  C07D239/42 ,  C07D239/46 ,  C07D239/48 ,  C07D295/00 ,  C07D401/04

Abstract: Compounds of the general formula are described:whereinR is hydrogen or halogen;R is hydrogen, halogen, lower alkyl or lower alkoxy;R is halogen, trifluoromethyl, lower alkoxy or lower alkyl;R /R are each independently hydrogen or lower alkyl;R is lower alkyl, lower alkoxy, amino, hydroxy, hydroxy-lower alkyl, -(CH2)n-piperazinyl, optionally substituted by lower alkyl, -(CH2)n-morpholinyl, -(CH2)n+1-imidazolyl, -O-(CH2)n+1-morpholinyl, -O-(CH2)n+1-piperidinyl, lower alkyl-sulfanyl, lower alkyl-sulfonyl, benzylamino, -NH-(CH2)n+1N(R )2, -(CH2)n-NH-(CH2)n+1N(R )2, -(CH2)n+1N(R )2, or -O-(CH2)n+1N(R )2, wherein R is hydrogen or lower alkyl;R is hydrogen;R and R or R and R may together be -CH=CH-CH=CH-, wherein R and R or R and R , respectively, together with the two carbon ring atoms to which they are attached form a fused ring, with the proviso that n for R is 1;n is independently 0-2; andX is -C(O)N(R )- or -N(R )C(O)-;and pharmaceutically acceptable acid addition salts thereof.

公开(公告)号：AT353881T

公开(公告)日：2007-03-15

申请号：AT01960225

申请日：2001-05-18

Applicant: HOFFMANN LA ROCHE

Inventor： GALLEY GUIDO ,  GOERGLER ANNICK ,  GODEL THIERRY ,  HECK REINHARD

IPC: C07D243/08 ,  A61K31/551 ,  A61K31/5517 ,  A61P1/04 ,  A61P1/08 ,  A61P9/00 ,  A61P11/06 ,  A61P13/10 ,  A61P17/02 ,  A61P19/02 ,  A61P25/00 ,  A61P25/06 ,  A61P27/02 ,  A61P29/00 ,  A61P37/08 ,  C07D243/14 ,  C07D401/06 ,  C07D401/14 ,  C07D403/06 ,  C07D409/06 ,  C07D487/04

Abstract: The invention relates to compounds of the formulawhereinR1, R2 are independently from each other aryl or heteroaryl, wherein the heteroaryl group contains one or two heteroatoms, selected from N, O, or S, and wherein the aryl or heteroaryl groups are optionally substituted by 1 to 3 substituents, which are independently from each other halogen, CF3, lower alkoxy or lower alkyl;R3 is hydrogen, lower alkyl, -(CH2)nN(R)2, -(CH2)n-heteroaryl or is a -(CH2)n-non aromatic heterocycle, which heterocycles are optionally substituted by halogen, CF3, lower alkoxy or lower alkyl;R4 is =O, =N(CH2)nCH3 or =N(CH2)nN(R)2;R3 and R4 may be together with the N and C atoms to which they are attached the group -CR5=N-N=; R5 is hydrogen, -(CH2)nN(R)2, -(CH2)n-heteroaryl or is a -(CH2)n-non aromatic heterocycle, which heterocycles are optionally substituted by halogen, CF3, lower alkoxy or lower alkyl;R is hydrogen or lower alkyl;n is 0, 1, 2 or 3;and pharmaceutically acceptable acid addition salts and enantiomeric forms thereof. The compounds are useful in the treatment of diseases, related to the NK-1 receptor.

公开(公告)号：MX2007000468A

公开(公告)日：2007-03-08

申请号：MX2007000468

申请日：2005-07-06

Applicant: HOFFMANN LA ROCHE

Inventor： GALLEY GUIDO ,  JAKOB-ROETNE ROLAND ,  KITAS ERIC ARGIRIOS

IPC: A61K31/55 ,  A61K31/00 ,  A61P35/00 ,  A61P25/28 ,  C07D223/08

Abstract: La invencion se refiere a compuestos de la formula general R2-R4 o alquilo en donde R' es arilo o heteroarilo, sustituido o sin sustituir por uno o mas sustituyentes, seleccionados del grupo consistente en halogeno, alquilo inferior, alquilo inferior sustituido por halogeno, -O-alquilo inferior sustituido por halogeno, NO2 o CN; y R2-R4 son hidrogeno, alquilo inferior inferior sustituido por halogeno; es cicloalquilo, sustituido o sin sustituir por CN, - C(O)OH o -C(O)O-alquilo inferior; o es arilo o heteroarilo, sustituido o sin sustituir por uno o mas sustituyentes, seleccionados del grupo consistente en halogeno, alquilo inferior, alquiloxi inferior, CN, nitro, amino, hidroxi, alquilo inferior sustituido por hidroxilo, alquilo inferior sustituido por halogeno, o estan sustituidos por -C(O)-NR'2, - (CR2)mC(O) R, - (CH2)mheterocicloalqu??lo, (CH2)mheteroarilo, sustituido o sin sustituir por - (CH2)malcoXilo inferior, alquilo inferior, (CH2)Mo bencilo o CH2OH, -O-C(O) -alquilo inferior, 0C(O) NR2, 0 (CH2)mC(O)OH, -0-alquinilo inferior, -O-alquilo inferior sustituido por halogeno, 0 (CH2)mheteroCiclilo, 0(CH2)mfeflilo, sustituido o sin sustituir por hidroxilo, 0(CH2)mheteroarilo, sustituido o sin sustituir por alquilo inferior, (CH2)mNHC(O)R, - (CH2)mNHS(O)2R, -s (O) 2-alquilo inferior, -s (O) 2-heterociclilo, -s (o) 2N1-I-cicloalquilo, o es cicloalquilo; es hidrogeno, alquilo inferior, alquiniloxilo inferior, hidroxi, cicloalquilo, heterocicloalquilo, que esta sustituido o sin sustituir por uno o mas sustituyentes, seleccionados de COOH, -C(O)O-alquilo inferior - CH2C(O)0-alquilo inferior, halogeno o alquilo inferior, o es fenilo, bencilo, heteroarilo, -(CH2)m-alcoxilo inferior o - (CI-{R)-C(O)O-a1qui1o inferior; es hidrogeno, cicloalquilo, que esta sustituido o sin sustituir por uno o mas sustituyentes, seleccionados de halogeno, o es alquilo inferior, alquilo inferior sustituido por halogeno, alquilo inferior sustituido por hidroxilo, - (CH2)-heterocicloalquilo, -NR2, heteroarilo, bencilo o - (CHR)m-C(O)O-alquilo inferior; R es hidrogeno o alquilo inferior; R6 es hidrogeno o alquilo inferior; X es -CHR-; m esO, 1,203; y sales acidas de adicion farmaceuticamente adecuadas, enantiomeros opticamente puros, racematos o mezclas diastereomericas para el tratamiento de la enfermedad de Alzheimer o canceres comunes.

公开(公告)号：AU2002342238B2

公开(公告)日：2007-01-25

申请号：AU2002342238

申请日：2002-05-06

Applicant: HOFFMANN LA ROCHE

Inventor： CAI HAI-YING ,  GALLEY GUIDO ,  KOLCZEWSKI SABINE ,  DILLON MICHAEL PATRICK ,  GOERGLER ANNICK ,  MUSZYNSKI-BARSY DAWN MARIE

IPC: C07D498/10 ,  A61K31/535 ,  A61K31/537 ,  A61P1/08 ,  A61P25/00 ,  A61P25/24 ,  A61P43/00

Abstract: The invention relates to compounds of the general formulawherein(R1)n is independently from from each other halogen, lower alkyl or lower alkoxy;R2 is hydrogen, lower alkyl, lower halogen-alkyl, -(CH2)m-OH, -(CH2)m-NR2, -(CH2)mO-lower alkyl, -(CH2)m-C(O)-NR2, or is -(CH2)m-6-membered heteroaryl, optionally substituted by one or more lower alkoxy, -(CH2)m-5 or 6-membered not aromatic heterocyclyl, optionally substituted by hydroxy or lower alkyl;R is hydrogen or lower alkyl and may be the same or different in case of R2;n is 0, 1, or 2;m is 0, 1, 2, 3 or 4;and pharmaceutically acceptable acid addition salts thereof. These compounds have a good affinity to the NK-1 receptor and they are therefore suitable for the treatment of diseases, related to this receptor.