公开(公告)号：CA2274201C

公开(公告)日：2010-02-09

申请号：CA2274201

申请日：1999-06-09

Applicant: HOFFMANN LA ROCHE

Inventor： ADAM GEO ,  CESURA ANDREA ,  JENCK FRANCOIS ,  KOLCZEWSKI SABINE ,  ROVER STEPHAN ,  WICHMANN JURGEN

IPC: C07D401/04 ,  C07D471/10 ,  A61K20060101 ,  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 ,  C07D471/20 ,  C07D487/12 ,  C07D498/10 ,  C07D513/10

Abstract: The present invention relates to compounds of the general formula (see formula I) wherein R1 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; bicyclo[6.2.0]dec-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; R2 is hydrogen; lower alkyl; =O or phenyl, optionally substituted by lower alkyl, halogen or alkoxy; ~ is cyclohexyl or phenyl, optionally substituted by lower alkyl, halogen or alkoxy; X is -CH(OH)-; -C(O)-; -CHR3-; -CR3=; -O-; -S-; -CH(COOR4)- or -C(COOR4)=; Y is -CH2-; -CH=; -CH(COOR4)-, -C(COOR4)=; or -C(CN)-; R3 is hydrogen or lower alkoxy; R4 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：SI1501804T1

公开(公告)日：2009-12-31

申请号：SI200331658

申请日：2003-04-14

Applicant: HOFFMANN LA ROCHE

Inventor： CESURA ANDREA ,  RODRIGUEZ SARMIENTO ROSA MARIA ,  SCALONE MICHELANGELO ,  THOMAS ANDREW WILLIAM ,  WYLER RENE

IPC: C07D217/00 ,  C07D217/04 ,  A61K31/00 ,  A61K31/472 ,  A61P25/00 ,  A61P25/16 ,  A61P25/28 ,  A61P43/00 ,  C07D217/24 ,  C07D405/06

公开(公告)号：AT440821T

公开(公告)日：2009-09-15

申请号：AT03725018

申请日：2003-04-14

Applicant: HOFFMANN LA ROCHE

Inventor： CESURA ANDREA ,  RODRIGUEZ SARMIENTO ROSA MARIA ,  SCALONE MICHELANGELO ,  THOMAS ANDREW ,  WYLER RENE

IPC: C07D217/04 ,  C07D217/24 ,  A61K31/472 ,  A61P25/16 ,  A61P25/28 ,  A61P43/00 ,  C07D405/06

Abstract: Disclosed are isoquinolino derivatives of the formulawherein Y is >C=O or -CH2-, Z is >C=O or -CH2-, and R , R and m are as defined herein as well as the pharmaceutically acceptable salts thereof. These compounds are MAO-B selective inhibitors useful, inter alia, in the treatment of Alzheimer's disease and/or senile dementia.

公开(公告)号：DE69826891T2

公开(公告)日：2005-11-24

申请号：DE69826891

申请日：1998-12-03

Applicant: HOFFMANN LA ROCHE

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

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

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：PL372226A1

公开(公告)日：2005-07-11

申请号：PL37222603

申请日：2003-01-27

Applicant: HOFFMANN LA ROCHE

Inventor： CESURA ANDREA ,  RODRIGUEZ SARMIENTO ROSA MARIA ,  THOMAS ANDREW WILLIAM ,  WYLER RENE

IPC: A61K31/44 ,  A61K31/455 ,  A61P3/04 ,  A61P25/00 ,  A61P25/02 ,  A61P25/18 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/32 ,  A61P25/34 ,  A61P43/00 ,  C07D213/81 ,  C07D213/82

Abstract: Disclosed are pyridine amido derivatives of the formulawherein X, Y, and R to R are as defined herein. These compounds are selective MAO-B inhibitors and are useful in treating diseases such as, for example, Alzheimer's and senile dementia. Also disclosed are pharmaceutical compositions containing such compounds and a method of preparing such compounds.

公开(公告)号：PA8572001A1

公开(公告)日：2003-12-10

申请号：PA8572001

申请日：2003-04-23

Applicant: HOFFMANN LA ROCHE

Inventor： WYLER RENE ,  THOMAS ANDREW WILLIAM ,  CESURA ANDREA ,  RODRIGUEZ SARMIENTO ROSA MARIA ,  SCALONE MICHELANGELO

IPC: C07D217/04 ,  A61K31/31 ,  A61K31/472 ,  A61P25/16 ,  A61P25/28 ,  A61P43/00 ,  C07D215/46 ,  C07D217/24 ,  C07D401/04 ,  C07D405/04 ,  C07D405/06

Abstract: ESTA INVENCION SE REFIERE A DERIVADOS DE ISOQUINOLINA DE FORMULA GENERAL EN DONDE Y ES >C=O O -CH2-, Z ES >C=O O -CH2-, Y R1, R2, Y M SON TAL COMO SE HAN DEFINIDO EN LA ESPECIFICACION, ASI COMO SUS SALES FARMACEUTICAMENTE ACEPTABLES. LA INVENCION ADEMAS SE REFIERE A MEDICAMENTOS QUE CONTIENEN ESTOS COMPUESTOS, UN PROCESO PARA SU PREPARACION ASI COMO SU USO PARA LA PREPARACION DE MEDICAMENTOS PARA EL TRATAMENTO O PREVENCION DE ENFERMEDADES EN QUE LOS INHIBIDORES DE LA MAO-B PUEDAN SER BENEFICIOSOS.

公开(公告)号：CA2483461A1

公开(公告)日：2003-11-06

申请号：CA2483461

申请日：2003-04-14

Applicant: HOFFMANN LA ROCHE

Inventor： CESURA ANDREA ,  WYLER RENE ,  THOMAS ANDREW WILLIAM ,  SCALONE MICHELANGELO ,  RODRIGUEZ SARMIENTO ROSA MARIA

IPC: C07D217/04 ,  A61K31/472 ,  A61P25/16 ,  A61P25/28 ,  A61P43/00 ,  C07D217/24 ,  C07D405/06

Abstract: This invention relates to isoquinolino derivatives of the general Formula (I ) wherein Y is >C=O or CH2-, Z is >C=O or CH2-, and R1, R2 and m are as defined in the specification, as well as their pharmaceutically acceptable salts. Th e invention further relates to medicaments containing these compounds, a proce ss for their preparation as well as their use for preparation of medicaments fo r the treatment or prevention of diseases in which MAO-B inhibitors might be beneficial.

公开(公告)号：PT963985E

公开(公告)日：2003-06-30

申请号：PT99110954

申请日：1999-06-07

Applicant: HOFFMANN LA ROCHE

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

IPC: A61K20060101 ,  A61K31/00 ,  A61K31/395 ,  A61K31/40 ,  A61K31/435 ,  A61K31/438 ,  A61K31/44 ,  A61K31/445 ,  A61P3/04 ,  A61P3/12 ,  A61P9/00 ,  A61P25/00 ,  A61P25/02 ,  C07D401/04 ,  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

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：ES2170446T3

公开(公告)日：2002-08-01

申请号：ES98122511

申请日：1998-11-27

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 ,  A61K31/44

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

公开(公告)号：PT970957E

公开(公告)日：2002-02-28

申请号：PT99110943

申请日：1999-06-07

Applicant: HOFFMANN LA ROCHE

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

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 ,  A61K31/445

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.