公开(公告)号：CA2232141C

公开(公告)日：2006-05-23

申请号：CA2232141

申请日：1997-04-09

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： FERNANDEZ-GADEA FRANCISCO JAVI ,  GIL-LOPETEGUI PILAR ,  MEERT THEO FRANS

IPC: C07D307/93 ,  A61K31/00 ,  A61K31/34 ,  A61K31/343 ,  A61K31/4025 ,  A61K31/4035 ,  A61K31/443 ,  A61K31/445 ,  A61K31/4465 ,  A61K31/4523 ,  A61K31/4525 ,  A61K31/495 ,  A61K31/496 ,  A61K31/535 ,  A61K31/5375 ,  A61K31/5377 ,  A61K31/55 ,  A61P1/00 ,  A61P1/14 ,  A61P9/00 ,  A61P9/02 ,  A61P25/06 ,  A61P25/18 ,  A61P25/22 ,  A61P25/24 ,  A61P25/30 ,  C07D405/02 ,  C07D405/06 ,  C07D491/048 ,  C07D493/04 ,  C07D493/10 ,  C07D495/04

Abstract: This invention concerns the compounds of formula (I), the N-oxide forms, the pharmaceutically acceptable addition salts and the stereoisomeric forms thereof, wherein n is zero to 6; p and q are zero to 4; r is zero to 5; R1 and R2 each independently are hydrogen; optionally substituted C1-6alkyl; C1-6alkylcarbonyl; halomethylcarbonyl; or R1 and R2 taken together with the nitrogen atom to which they are attached may form a morpholinyl ring or an optionally substituted heterocycle; each R3 and R4 independently are halo, cyano, hydroxy, halomethyl, halomethoxy, carboxyl, nitro, amino, mono- or di(C1-6alkyl)amino, C1-6alkylcarbonylamino, aminosulfonyl, mono- or di(C1-6alkyl)aminosulfonyl, C1-6alkyl, C1-6alkyloxy, C1-6alkylcarbonyl, C1- 6alkyloxycarbonyl; each R5 independently is C1-6alkyl, cyano or halomethyl; X is CR6R7, NR8, O, S, S(~O) or S(~O)2; aryl is optionally substituted phenyl; provided that the compound is other than (~)-3,3a,8,12b-tetrahydro-N-methyl-2H-dibenzo[3,4:6,7]-cyclohepta[1,2-b]-fur an- 2-methanamine oxalic acid. The compounds of formula (I) may be used as therapeutic agents in the treatment or the prevention of CNS disorders, cardiovascular disorders or gastrointestinal disorders.

公开(公告)号：PL190960B1

公开(公告)日：2006-02-28

申请号：PL32857597

申请日：1997-04-09

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： GIL-LOPETEGUI PILAR ,  FERNANDEZ-GADEA FRANCISCO JAVI ,  MEERT THEO FRANZ

IPC: C07D307/93 ,  A61K31/00 ,  A61K31/34 ,  A61K31/343 ,  A61K31/4025 ,  A61K31/4035 ,  A61K31/443 ,  A61K31/445 ,  A61K31/4465 ,  A61K31/4523 ,  A61K31/4525 ,  A61K31/495 ,  A61K31/496 ,  A61K31/535 ,  A61K31/5375 ,  A61K31/5377 ,  A61K31/55 ,  A61P1/00 ,  A61P1/14 ,  A61P9/00 ,  A61P9/02 ,  A61P25/00 ,  A61P25/06 ,  A61P25/18 ,  A61P25/22 ,  A61P25/24 ,  A61P25/30 ,  C07D405/02 ,  C07D405/06 ,  C07D491/048 ,  C07D493/04 ,  C07D493/10 ,  C07D495/04

公开(公告)号：NO317156B1

公开(公告)日：2004-08-30

申请号：NO981076

申请日：1998-03-11

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： FERNANDEZ-GADEA FRANCISCO JAVIER ,  GIL-LOPETEGUI PILAR ,  MEERT THEO FRANS

IPC: C07D307/93 ,  A61K31/00 ,  A61K31/34 ,  A61K31/343 ,  A61K31/4025 ,  A61K31/4035 ,  A61K31/443 ,  A61K31/445 ,  A61K31/4465 ,  A61K31/4523 ,  A61K31/4525 ,  A61K31/495 ,  A61K31/496 ,  A61K31/535 ,  A61K31/5375 ,  A61K31/5377 ,  A61K31/55 ,  A61P1/00 ,  A61P1/14 ,  A61P9/00 ,  A61P9/02 ,  A61P25/06 ,  A61P25/18 ,  A61P25/22 ,  A61P25/24 ,  A61P25/30 ,  C07D405/02 ,  C07D405/06 ,  C07D491/048 ,  C07D493/04 ,  C07D493/10 ,  C07D495/04

Abstract: PCT No. PCT/EP97/01829 Sec. 371 Date Oct. 6, 1998 Sec. 102(e) Date Oct. 6, 1998 PCT Filed Apr. 9, 1997 PCT Pub. No. WO97/38991 PCT Pub. Date Oct. 23, 1997This invention concerns the compounds of formula (I), the N-oxide forms, the pharmaceutically acceptable addition salts and the stereoisomeric forms thereof, wherein n is zero to 6; p and q are zero to 4; r is zero to 5; R1 and R2 each independently are hydrogen; optionally substituted C1-6alkyl; C1-6alkylcarbonyl; halomethylcarbonyl; or R1 and R2 taken together with the nitrogen atom to which they are attached may form a morpholinyl ring or an optionally substituted heterocycle; each R3 and R4 independently are halo, cyano, hydroxy, halomethyl, halomethoxy, carboxyl, nitro, amino, mono- or di(C1-6alkyl)amino, C1-6alkylcarbonylamino, aminosulfonyl, mono- or di(C1-6alkyl)aminosulfonyl, C1-6alkyl, C1-6alkyloxy, C1-6alkylcarbonyl, C1-6alkyloxycarbonyl; each R5 independently is C1-6alkyl, cyano or halomethyl; X is CR6R7, NR8, O, S, S(=O) or S(=O)2; aryl is optionally substituted phenyl; provided that the compound is other than (+/-)-3,3a,8,12b-tetrahydro-N-methyl-2H-dibenzo[3,4:6,7]-cyclohepta[1,2-b]-furan-2-methanamine oxalic acid. The compounds of formula (I) may be used as therapeutic agents in the treatment or the prevention of CNS disorders, cardiovascular disorders or gastrointestinal disorders.

公开(公告)号：CY2382B1

公开(公告)日：2004-06-04

申请号：CY0300077

申请日：2003-11-04

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： GIL-LOPETEGUI PILAR ,  FERNANDEZ-GADEA FRANCISCO JAVI ,  MEERT THEO FRANZ

IPC: A61K31/00 ,  A61K31/34 ,  A61K31/343 ,  A61K31/4025 ,  A61K31/4035 ,  A61K31/443 ,  A61K31/445 ,  A61K31/4465 ,  A61K31/4523 ,  A61K31/4525 ,  A61K31/495 ,  A61K31/496 ,  A61K31/535 ,  A61K31/5375 ,  A61K31/5377 ,  A61K31/55 ,  A61P1/00 ,  A61P1/14 ,  A61P9/00 ,  A61P9/02 ,  A61P25/06 ,  A61P25/18 ,  A61P25/22 ,  A61P25/24 ,  A61P25/30 ,  C07D307/93 ,  C07D405/02 ,  C07D405/06 ,  C07D491/048 ,  C07D493/04 ,  C07D493/10 ,  C07D495/04

Abstract: PCT No. PCT/EP97/01829 Sec. 371 Date Oct. 6, 1998 Sec. 102(e) Date Oct. 6, 1998 PCT Filed Apr. 9, 1997 PCT Pub. No. WO97/38991 PCT Pub. Date Oct. 23, 1997This invention concerns the compounds of formula (I), the N-oxide forms, the pharmaceutically acceptable addition salts and the stereoisomeric forms thereof, wherein n is zero to 6; p and q are zero to 4; r is zero to 5; R1 and R2 each independently are hydrogen; optionally substituted C1-6alkyl; C1-6alkylcarbonyl; halomethylcarbonyl; or R1 and R2 taken together with the nitrogen atom to which they are attached may form a morpholinyl ring or an optionally substituted heterocycle; each R3 and R4 independently are halo, cyano, hydroxy, halomethyl, halomethoxy, carboxyl, nitro, amino, mono- or di(C1-6alkyl)amino, C1-6alkylcarbonylamino, aminosulfonyl, mono- or di(C1-6alkyl)aminosulfonyl, C1-6alkyl, C1-6alkyloxy, C1-6alkylcarbonyl, C1-6alkyloxycarbonyl; each R5 independently is C1-6alkyl, cyano or halomethyl; X is CR6R7, NR8, O, S, S(=O) or S(=O)2; aryl is optionally substituted phenyl; provided that the compound is other than (+/-)-3,3a,8,12b-tetrahydro-N-methyl-2H-dibenzo[3,4:6,7]-cyclohepta[1,2-b]-furan-2-methanamine oxalic acid. The compounds of formula (I) may be used as therapeutic agents in the treatment or the prevention of CNS disorders, cardiovascular disorders or gastrointestinal disorders.

公开(公告)号：PL183686B1

公开(公告)日：2002-06-28

申请号：PL31993995

申请日：1995-10-25

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： SIPIDO VICTOR K ,  FERNANDEZ-GADEA FRANCISCO J ,  ANDRES-GIL JOSE I ,  MEERT THEO F ,  GIL-LOPETEGUI PILAR

IPC: A61K31/535 ,  A61K31/55 ,  A61P9/00 ,  A61P25/00 ,  A61P25/18 ,  A61P25/24 ,  A61P25/26 ,  C07D223/20 ,  C07D223/30 ,  C07D261/00 ,  C07D498/04 ,  A61K31/553

Abstract: This invention concerns the compounds of formula (I), the pharmaceutically acceptable salts and stereoisomeric forms thereof, and also the N-oxide forms thereof. (I) wherein: R1 and R2 each independently are hydrogen; C1-6alkyl; C1-6alkylcarbonyl; trihalomethylcarbonyl; C1-6alkyl substituted with hydroxy, C1-6alkyloxy, carboxyl, C1-6alkylcarbonyloxy, C1-6alkyloxycarbonyl or aryl; or R1 and R2 taken together with the nitrogen atom to which they are attached may form a morpholinyl ring or an optionally substituted heterocycle; R3, R4, R5, R6, R9, R10, R11 or R12 each independently are hydrogen, halo, cyano, hydroxy, trifluoromethyl, trifluoromethoxy, carboxyl, nitro, amino, mono- or di(C1-6alkyl)-amino, C1-6alkylcarbonylamino, aminosulfonyl, mono- or di(C1-6alkyl)-aminosulfonyl, C1-6alkyl, C1-6alkyloxy, C1-6alkylcarbonyl, C1-6alkyloxy-carbonyl; R7 and R8 are each independently hydrogen, hydroxy, C1-6alkyl, C1-6alkyloxy or R7 and R8 taken together may form mono- or di(cyano)methylene, or together with the carbon atom to which they are attached form a carbonyl or a spiro substituent; or R7 and R8 taken together may form methylene; R13 is hydrogen, C1-6alkyl, or trifluoromethyl; R14 is hydrogen, C1-6alkyl, cyano, or trifluoromethyl; n is zero to 6. These compounds were tested as mCPP-antagonists in rats. The compounds of formula (I) may be used as therapeutic agents in the treatment or the prevention of CNS disorders, cardiovascular disorders or gastrointestinal disorders.

公开(公告)号：NZ503294A

公开(公告)日：2001-08-31

申请号：NZ50329498

申请日：1998-10-06

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： ANDRES-GIL JOSE IGNACIO ,  FERNANDEZ-GADEA FRANCISCO JAVI ,  GIL-LOPETEGUI PILAR ,  DIAZ-MARTINEZ ADOLFO

IPC: A61K31/34 ,  A61K31/343 ,  A61K31/4427 ,  A61K31/443 ,  A61K31/445 ,  A61K31/4525 ,  A61K31/495 ,  A61K31/496 ,  A61K31/535 ,  A61K31/5377 ,  A61K31/55 ,  A61P25/00 ,  A61P25/06 ,  A61P25/18 ,  A61P25/20 ,  A61P25/22 ,  A61P25/24 ,  A61P25/30 ,  C07D307/93 ,  C07D401/06 ,  C07D405/06 ,  C07D493/04

Abstract: Compounds of formula (I) may be used in medicaments for the treatment of anxiety, psychosis, schizophrenia, depression, migraine, sleep disorders and addictive properties of drugs of abuse. In formula (I); n is zero, 1, 2, 3, 4, 5 or 6; X is CH2 or O; R1 and R2 each independently are hydrogen, C1-6alkyl, C1-6alkylcarbonyl, halomethylcarbonyl or C1-6alkyl substituted with hydroxy, C1-6alkyloxy, carboxyl, C1-6alkylcarbonyloxy, C1-6alkyloxycarbonyl or aryl; or R1 and R2 taken together with the nitrogen atom to which they are attached may form a morpholinyl ring or radical depicted above, wherein R9, R10, R11 and R12 independently are hydrogen, halo, halomethyl or C1-6alkyl m is 0, 1, 2 or 3; R13, R14, R15 and R16 each independently are hydrogen, C1-6alkyl, aryl or arylcarbonyl; or R15 and R16 taken together may form a bivalent radical C4-5alkanediyl; R17 is hydrogen, C1-6 alkyl, C1-6alkylcarbonyl, halomethylcarbonyl, C1-6alkoxycarbonyl, aryl, di(aryl)methyl or C1-6alkyl substituted with hydroxy, C1-6 alkyloxy, carboxyl, C1-6alkylcarbonyloxy, C1-6alkyloxycarbonyl or aryl; R3 and R4 are both halogen; or R3 is halogen and R4 is hydrogen; or R3 is hydrogen and R4 is halogen; and aryl is phenyl or phenyl substituted with 1, 2 or 3 substituents selected from halo, hydroxy, C1-6alkyl and halomethyl.

公开(公告)号：DE69520070D1

公开(公告)日：2001-03-15

申请号：DE69520070

申请日：1995-10-25

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： SIPIDO KAREL ,  FERNANDEZ-GADEA FRANCISCO JAVI ,  ANDRES-GIL JOSE IGNACIO ,  MEERT FRANS ,  GIL-LOPETEGUI PILAR

IPC: A61K31/535 ,  A61K31/55 ,  A61P9/00 ,  A61P25/00 ,  A61P25/18 ,  A61P25/24 ,  A61P25/26 ,  C07D223/20 ,  C07D223/30 ,  C07D261/00 ,  C07D498/04

Abstract: This invention concerns the compounds of formula (I), the pharmaceutically acceptable salts and stereoisomeric forms thereof, and also the N-oxide forms thereof. (I) wherein: R1 and R2 each independently are hydrogen; C1-6alkyl; C1-6alkylcarbonyl; trihalomethylcarbonyl; C1-6alkyl substituted with hydroxy, C1-6alkyloxy, carboxyl, C1-6alkylcarbonyloxy, C1-6alkyloxycarbonyl or aryl; or R1 and R2 taken together with the nitrogen atom to which they are attached may form a morpholinyl ring or an optionally substituted heterocycle; R3, R4, R5, R6, R9, R10, R11 or R12 each independently are hydrogen, halo, cyano, hydroxy, trifluoromethyl, trifluoromethoxy, carboxyl, nitro, amino, mono- or di(C1-6alkyl)-amino, C1-6alkylcarbonylamino, aminosulfonyl, mono- or di(C1-6alkyl)-aminosulfonyl, C1-6alkyl, C1-6alkyloxy, C1-6alkylcarbonyl, C1-6alkyloxy-carbonyl; R7 and R8 are each independently hydrogen, hydroxy, C1-6alkyl, C1-6alkyloxy or R7 and R8 taken together may form mono- or di(cyano)methylene, or together with the carbon atom to which they are attached form a carbonyl or a spiro substituent; or R7 and R8 taken together may form methylene; R13 is hydrogen, C1-6alkyl, or trifluoromethyl; R14 is hydrogen, C1-6alkyl, cyano, or trifluoromethyl; n is zero to 6. These compounds were tested as mCPP-antagonists in rats. The compounds of formula (I) may be used as therapeutic agents in the treatment or the prevention of CNS disorders, cardiovascular disorders or gastrointestinal disorders.

公开(公告)号：SK4712000A3

公开(公告)日：2000-10-09

申请号：SK4712000

申请日：1998-10-06

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： ANDRES-GIL JOSE IGNACIO ,  FERNANDEZ-GADEA FRANCISCO JAVI ,  GIL-LOPETEGUI PILAR ,  DIAZ-MARTINEZ ADOLFO

IPC: A61K31/34 ,  A61K31/343 ,  A61K31/4427 ,  A61K31/443 ,  A61K31/445 ,  A61K31/4525 ,  A61K31/495 ,  A61K31/496 ,  A61K31/535 ,  A61K31/5377 ,  A61K31/55 ,  A61P25/00 ,  A61P25/06 ,  A61P25/18 ,  A61P25/20 ,  A61P25/22 ,  A61P25/24 ,  A61P25/30 ,  C07D307/93 ,  C07D401/06 ,  C07D405/06 ,  C07D493/04

Abstract: This invention concerns the compounds of formula (I),the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein n is zero, 1, 2, 3, 4, 5 or 6; X is CH2 or O; R and R each independently are hydrogen, C1-6alkyl, C1-6alkylcarbonyl, halomethylcarbonyl or C1-6alkyl substituted with hydroxy, C1-6alkyloxy, carboxyl, C1-6alkylcarbonyloxy, C1-6alkyloxycarbonyl or aryl; or R and R taken together with the nitrogen atom to which they are attached may form a morpholinyl ring or an optionally substituted heterocycle; R and R are both halogen; or R is halogen and R is hydrogen; or R is hydrogen and R is halogen; and aryl is phenyl or phenyl substituted with 1, 2 or 3 substituents selected from halo, hydroxy, C1-6alkyl and halomethyl. The compounds of formula (I) may be used as therapeutic agents.

公开(公告)号：CZ20001136A3

公开(公告)日：2000-08-16

申请号：CZ20001136

申请日：1998-10-06

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： ANDR S-GIL JOS IGNACIO ,  FERNANDEZ-GADEA FRANCISCO JAVI ,  GIL-LOPETEGUI PILAR ,  DIAZ-MARTINEZ ADOLFO

IPC: A61K31/34 ,  A61K31/343 ,  A61K31/4427 ,  A61K31/443 ,  A61K31/445 ,  A61K31/4525 ,  A61K31/495 ,  A61K31/496 ,  A61K31/535 ,  A61K31/5377 ,  A61K31/55 ,  A61P25/00 ,  A61P25/06 ,  A61P25/18 ,  A61P25/20 ,  A61P25/22 ,  A61P25/24 ,  A61P25/30 ,  C07D307/93 ,  C07D401/06 ,  C07D405/06 ,  C07D493/04

Abstract: This invention concerns the compounds of formula (I),the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein n is zero, 1, 2, 3, 4, 5 or 6; X is CH2 or O; R and R each independently are hydrogen, C1-6alkyl, C1-6alkylcarbonyl, halomethylcarbonyl or C1-6alkyl substituted with hydroxy, C1-6alkyloxy, carboxyl, C1-6alkylcarbonyloxy, C1-6alkyloxycarbonyl or aryl; or R and R taken together with the nitrogen atom to which they are attached may form a morpholinyl ring or an optionally substituted heterocycle; R and R are both halogen; or R is halogen and R is hydrogen; or R is hydrogen and R is halogen; and aryl is phenyl or phenyl substituted with 1, 2 or 3 substituents selected from halo, hydroxy, C1-6alkyl and halomethyl. The compounds of formula (I) may be used as therapeutic agents.

公开(公告)号：CZ324398A3

公开(公告)日：1999-01-13

申请号：CZ324398

申请日：1997-04-09

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： GIL-LOPETEGUI PILAR ,  FERNANDEZ-GADEA FRANCISCO JAVI ,  MEERT THEO FRANS

IPC: A61K31/00 ,  A61K31/34 ,  A61K31/343 ,  A61K31/4025 ,  A61K31/4035 ,  A61K31/443 ,  A61K31/445 ,  A61K31/4465 ,  A61K31/4523 ,  A61K31/4525 ,  A61K31/495 ,  A61K31/496 ,  A61K31/535 ,  A61K31/5375 ,  A61K31/5377 ,  A61K31/55 ,  A61P1/00 ,  A61P1/14 ,  A61P9/00 ,  A61P9/02 ,  A61P25/06 ,  A61P25/18 ,  A61P25/22 ,  A61P25/24 ,  A61P25/30 ,  C07D307/93 ,  C07D405/02 ,  C07D405/06 ,  C07D491/048 ,  C07D493/04 ,  C07D493/10 ,  C07D495/04

Abstract: PCT No. PCT/EP97/01829 Sec. 371 Date Oct. 6, 1998 Sec. 102(e) Date Oct. 6, 1998 PCT Filed Apr. 9, 1997 PCT Pub. No. WO97/38991 PCT Pub. Date Oct. 23, 1997This invention concerns the compounds of formula (I), the N-oxide forms, the pharmaceutically acceptable addition salts and the stereoisomeric forms thereof, wherein n is zero to 6; p and q are zero to 4; r is zero to 5; R1 and R2 each independently are hydrogen; optionally substituted C1-6alkyl; C1-6alkylcarbonyl; halomethylcarbonyl; or R1 and R2 taken together with the nitrogen atom to which they are attached may form a morpholinyl ring or an optionally substituted heterocycle; each R3 and R4 independently are halo, cyano, hydroxy, halomethyl, halomethoxy, carboxyl, nitro, amino, mono- or di(C1-6alkyl)amino, C1-6alkylcarbonylamino, aminosulfonyl, mono- or di(C1-6alkyl)aminosulfonyl, C1-6alkyl, C1-6alkyloxy, C1-6alkylcarbonyl, C1-6alkyloxycarbonyl; each R5 independently is C1-6alkyl, cyano or halomethyl; X is CR6R7, NR8, O, S, S(=O) or S(=O)2; aryl is optionally substituted phenyl; provided that the compound is other than (+/-)-3,3a,8,12b-tetrahydro-N-methyl-2H-dibenzo[3,4:6,7]-cyclohepta[1,2-b]-furan-2-methanamine oxalic acid. The compounds of formula (I) may be used as therapeutic agents in the treatment or the prevention of CNS disorders, cardiovascular disorders or gastrointestinal disorders.