公开(公告)号：DE69714980T2

公开(公告)日：2003-04-10

申请号：DE69714980

申请日：1997-04-09

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： ANDRES-GIL JOSE IGNACIO ,  MARTINEZ-JIMENEZ PEDRO CAMPO D ,  FERNANDEZ-GADEA FRANCISCO CAMP ,  SIPIDO VICTOR KAREL

IPC: A61K31/00 ,  A61K31/55 ,  A61K31/551 ,  A61K31/5513 ,  A61K31/553 ,  A61P1/00 ,  A61P9/00 ,  A61P9/12 ,  A61P25/06 ,  A61P25/18 ,  A61P25/20 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P43/00 ,  C07D237/30 ,  C07D471/04 ,  C07D487/04 ,  C07D495/04 ,  C07D498/04 ,  C07D498/14 ,  C07D498/16

Abstract: PCT No. PCT/EP97/01830 Sec. 371 Date Oct. 6, 1998 Sec. 102(e) Date Oct. 6, 1998 PCT Filed Apr. 9, 1997 PCT Pub. No. WO97/39001 PCT Pub. Date Oct. 23, 1997This 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 to 6; p is zero to 3; q is zero to 3; r is zero to 3; R1 and R2 each independently are hydrogen; optionally substituted C1-6alkyl; C1-6alkylcarbonyl; trihalomethylcarbonyl; 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, trihalomethyl, trihalomethoxy, carboxyl, nitro, amino, mono- or di(C1-6alkyl)amino, C1-6alkylcarbonylamino, aminosulfonyl, mono- or di(C1-6alkyl)-aminosulfonyl, C1-6alkyl, C1-6alkyloxy, C1-6alkylcarbonyl or C1-6alkyloxycarbonyl; each R5 independently is C1-6alkyl, cyano or trihalomethyl; X is CR6R7, NR8, O, S, S(=O) or S(=O)2; each independently represents a bivalent aromatic heterocycle wherein the heterocycle may be selected from the group consisting of pyrrole, pyrrazole, imidazole, triazole, furane, thiophene, isoxazole, oxazole, isothiazole, thiazole, pyridine, pyridazine, pyrimidine, pyrazine and triazine; or one of the two bivalent aromatic heterocycles in the compounds of formula (I) may be 1,2-benzenediyl; and aryl is optionally substituted phenyl; it further relates to compositions comprising thesae compounds, as well as their use as therapeutic agents in the treatment or the prevention of CNS disorders, cardiovascular disorders or gastrointestinal disorders.

公开(公告)号：ES2182064T3

公开(公告)日：2003-03-01

申请号：ES97919344

申请日：1997-04-09

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： ANDRES-GIL JOSE IGNACIO ,  MARTINEZ-JIMENEZ PEDRO ,  FERNANDEZ-GADEA FRANCISCO ,  SIPIDO VICTOR KAREL

IPC: A61K31/00 ,  A61K31/55 ,  A61K31/551 ,  A61K31/5513 ,  A61K31/553 ,  A61P1/00 ,  A61P9/00 ,  A61P9/12 ,  A61P25/06 ,  A61P25/18 ,  A61P25/20 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P43/00 ,  C07D237/30 ,  C07D471/04 ,  C07D487/04 ,  C07D495/04 ,  C07D498/04 ,  C07D498/14 ,  C07D498/16

Abstract: PCT No. PCT/EP97/01830 Sec. 371 Date Oct. 6, 1998 Sec. 102(e) Date Oct. 6, 1998 PCT Filed Apr. 9, 1997 PCT Pub. No. WO97/39001 PCT Pub. Date Oct. 23, 1997This 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 to 6; p is zero to 3; q is zero to 3; r is zero to 3; R1 and R2 each independently are hydrogen; optionally substituted C1-6alkyl; C1-6alkylcarbonyl; trihalomethylcarbonyl; 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, trihalomethyl, trihalomethoxy, carboxyl, nitro, amino, mono- or di(C1-6alkyl)amino, C1-6alkylcarbonylamino, aminosulfonyl, mono- or di(C1-6alkyl)-aminosulfonyl, C1-6alkyl, C1-6alkyloxy, C1-6alkylcarbonyl or C1-6alkyloxycarbonyl; each R5 independently is C1-6alkyl, cyano or trihalomethyl; X is CR6R7, NR8, O, S, S(=O) or S(=O)2; each independently represents a bivalent aromatic heterocycle wherein the heterocycle may be selected from the group consisting of pyrrole, pyrrazole, imidazole, triazole, furane, thiophene, isoxazole, oxazole, isothiazole, thiazole, pyridine, pyridazine, pyrimidine, pyrazine and triazine; or one of the two bivalent aromatic heterocycles in the compounds of formula (I) may be 1,2-benzenediyl; and aryl is optionally substituted phenyl; it further relates to compositions comprising thesae compounds, as well as their use as therapeutic agents in the treatment or the prevention of CNS disorders, cardiovascular disorders or gastrointestinal disorders.

公开(公告)号：DK0892804T3

公开(公告)日：2002-12-02

申请号：DK97919344

申请日：1997-04-09

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： ANDRES-GIL JOSE IGNACIO ,  MARTINEZ-JIMENEZ PEDRO ,  FERNANDEZ-GADEA FRANCISCO ,  SIPIDO VICTOR KAREL

IPC: A61K31/00 ,  A61K31/55 ,  A61K31/551 ,  A61K31/5513 ,  A61K31/553 ,  A61P1/00 ,  A61P9/00 ,  A61P9/12 ,  A61P25/06 ,  A61P25/18 ,  A61P25/20 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P43/00 ,  C07D237/30 ,  C07D471/04 ,  C07D487/04 ,  C07D495/04 ,  C07D498/04 ,  C07D498/14 ,  C07D498/16

Abstract: PCT No. PCT/EP97/01830 Sec. 371 Date Oct. 6, 1998 Sec. 102(e) Date Oct. 6, 1998 PCT Filed Apr. 9, 1997 PCT Pub. No. WO97/39001 PCT Pub. Date Oct. 23, 1997This 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 to 6; p is zero to 3; q is zero to 3; r is zero to 3; R1 and R2 each independently are hydrogen; optionally substituted C1-6alkyl; C1-6alkylcarbonyl; trihalomethylcarbonyl; 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, trihalomethyl, trihalomethoxy, carboxyl, nitro, amino, mono- or di(C1-6alkyl)amino, C1-6alkylcarbonylamino, aminosulfonyl, mono- or di(C1-6alkyl)-aminosulfonyl, C1-6alkyl, C1-6alkyloxy, C1-6alkylcarbonyl or C1-6alkyloxycarbonyl; each R5 independently is C1-6alkyl, cyano or trihalomethyl; X is CR6R7, NR8, O, S, S(=O) or S(=O)2; each independently represents a bivalent aromatic heterocycle wherein the heterocycle may be selected from the group consisting of pyrrole, pyrrazole, imidazole, triazole, furane, thiophene, isoxazole, oxazole, isothiazole, thiazole, pyridine, pyridazine, pyrimidine, pyrazine and triazine; or one of the two bivalent aromatic heterocycles in the compounds of formula (I) may be 1,2-benzenediyl; and aryl is optionally substituted phenyl; it further relates to compositions comprising thesae compounds, as well as their use as therapeutic agents in the treatment or the prevention of CNS disorders, cardiovascular disorders or gastrointestinal disorders.

公开(公告)号：HU221608B

公开(公告)日：2002-11-28

申请号：HU9901875

申请日：1997-04-09

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： ANDRES-GIL JOSE IGNACIO ,  FERNANDEZ-GADEA FRANCISCO JAVI ,  MARTINEZ PEDRO ,  SIPIDO VICTOR KAREL

IPC: A61K31/00 ,  A61K31/55 ,  A61K31/551 ,  A61K31/5513 ,  A61K31/553 ,  A61P1/00 ,  A61P9/00 ,  A61P9/12 ,  A61P25/06 ,  A61P25/18 ,  A61P25/20 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P43/00 ,  C07D237/30 ,  C07D471/04 ,  C07D487/04 ,  C07D495/04 ,  C07D498/04 ,  C07D498/14 ,  C07D498/16

Abstract: PCT No. PCT/EP97/01830 Sec. 371 Date Oct. 6, 1998 Sec. 102(e) Date Oct. 6, 1998 PCT Filed Apr. 9, 1997 PCT Pub. No. WO97/39001 PCT Pub. Date Oct. 23, 1997This 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 to 6; p is zero to 3; q is zero to 3; r is zero to 3; R1 and R2 each independently are hydrogen; optionally substituted C1-6alkyl; C1-6alkylcarbonyl; trihalomethylcarbonyl; 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, trihalomethyl, trihalomethoxy, carboxyl, nitro, amino, mono- or di(C1-6alkyl)amino, C1-6alkylcarbonylamino, aminosulfonyl, mono- or di(C1-6alkyl)-aminosulfonyl, C1-6alkyl, C1-6alkyloxy, C1-6alkylcarbonyl or C1-6alkyloxycarbonyl; each R5 independently is C1-6alkyl, cyano or trihalomethyl; X is CR6R7, NR8, O, S, S(=O) or S(=O)2; each independently represents a bivalent aromatic heterocycle wherein the heterocycle may be selected from the group consisting of pyrrole, pyrrazole, imidazole, triazole, furane, thiophene, isoxazole, oxazole, isothiazole, thiazole, pyridine, pyridazine, pyrimidine, pyrazine and triazine; or one of the two bivalent aromatic heterocycles in the compounds of formula (I) may be 1,2-benzenediyl; and aryl is optionally substituted phenyl; it further relates to compositions comprising thesae compounds, as well as their use as therapeutic agents in the treatment or the prevention of CNS disorders, cardiovascular disorders or gastrointestinal disorders.

公开(公告)号：GR3035680T3

公开(公告)日：2001-06-29

申请号：GR20010400530

申请日：2001-03-30

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： SIPIDO VICTOR KAREL ,  FERNANDEZ-GADEA FRANCISCO JAVI ,  ANDRES-GIL JOSE IGNACIO ,  MEERT THEO 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：AT199087T

公开(公告)日：2001-02-15

申请号：AT95937006

申请日：1995-10-25

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： SIPIDO VICTOR KAREL ,  FERNANDEZ-GADEA FRANCISCO JAVI ,  ANDRES-GIL JOSE IGNACIO ,  MEERT THEO 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 ,  C07D223/00

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：AU704285B2

公开(公告)日：1999-04-15

申请号：AU3924995

申请日：1995-10-25

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： SIPIDO VICTOR KAREL ,  FERNANDEZ-GADEA FRANCISCO JAVI ,  ANDRES-GIL JOSE IGNACIO ,  MEERT THEO 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：PL319939A1

公开(公告)日：1997-09-01

申请号：PL31993995

申请日：1995-10-25

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： SIPIDO VICTOR KAREL ,  FERNANDEZ-GADEA FRANCISCO JAVI ,  ANDRES-GIL JOSE IGNACIO ,  MEERT THEO 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：MX9703250A

公开(公告)日：1997-07-31

申请号：MX9703250

申请日：1995-10-25

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： GADEA FRANCISCO JAVIER FERNAND ,  SIPIDO VICTOR KAREL ,  GIL JOSE IGNACIO ANDRES ,  MEERT THEO FRANS

IPC: C07D498/04 ,  C07D513/04 ,  A61K31/535 ,  C07D261/00 ,  C07D267/00

Abstract: Esta invencion se refiere a los compuestos de formula (I), las sales farmacéuticamente aceptables y las formas estereoisoméricas de las mismas, y también las formas de N-oxido de las mismas. En dicha formula, R1 y R2 son cada uno independientemente hidrogeno; C1-6 alquilo; C1-6 alquilcarbonilo; trihalometilcarbonilo; C1-6 alquilo sustituido con hidroxi, C1-6 alquiloxi, carboxilo, C1-6 alquilcarboniloxi, C1-6 alquiloxicarbonilo o arilo; o R1 y R2 considerados juntos con el átomo de nitrogeno al cual están unidos pueden formar un anillo de morfolinilo o un heterociclo sustituido opcionalmente; R3 y R10 son cada uno independientemente hidrogeno, halogeno, ciano, hidroxi, trifluorometilo, trifluorometoxi, carboxilo, nitro, amino, mono- o di(C1-6alquil)amino, C1-6 alquilcarbonilamino, aminosulfonilo, mono- o di(C1-6 alquil)-aminosulfonilo, C1-6 alquilo, C1-6 alquiloxi, C1-6 alquilcarbonilo, C1-6 alquiloxicarbonilo; R11 es hidrogeno, C1-6 alquilo o trifluorometilo; R12 es hidrogeno, C1-6 alquilo, ciano o trifluorometilo; n es 0 a 6; y X es 0,S,S(-O) o S(=O)2. Los compuestos de formula (I) pueden utilizarse como agentes terapéuticos en el tratamiento o la prevencion de trastornos del SNC, trastornos cardiovasculares o trastornos gastrointestinales.

公开(公告)号：ZA9509216B

公开(公告)日：1997-04-30

申请号：ZA9509216

申请日：1995-10-31

Applicant: JANSSEN PHARMACEUTICA NV

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

IPC: A61K31/535 ,  A61K31/55 ,  A61K31/553 ,  A61K31/554 ,  A61P9/00 ,  A61P25/00 ,  A61P25/18 ,  A61P25/24 ,  A61P25/26 ,  C07D261/20 ,  C07D267/16 ,  C07D498/04 ,  C07D513/04 ,  C07D ,  A61K

CPC classification number: C07D513/04