公开(公告)号：CA2462953A1

公开(公告)日：2003-04-24

申请号：CA2462953

申请日：2002-10-10

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： JANSSENS FRANS EDUARD ,  LEENAERTS JOSEPH ELISABETH ,  FERNANDEZ-GADEA FRANCISCO JAVI ,  GOMEZ-SANCHEZ ANTONIO ,  MEERT THEO FRANS

IPC: A61K31/445 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/496 ,  A61K31/506 ,  A61P1/00 ,  A61P1/04 ,  A61P1/12 ,  A61P11/00 ,  A61P11/06 ,  A61P13/10 ,  A61P17/06 ,  A61P19/02 ,  A61P25/02 ,  A61P25/04 ,  A61P29/00 ,  A61P43/00 ,  C07D401/04 ,  C07D401/14 ,  C07D413/14 ,  C07D417/14

Abstract: The present invention relates to novel 4-phenyl-4-[1H-imidazol-2-yl]- piperidine derivatives according to Formula (I), the pharmaceutically acceptable acid or base addition salts thereof, the stereochemically isomeri c forms thereof, the tautomeric forms thereof and the N-oxide forms thereof. I n particular are claimed compounds according to Formula (I) in which A=B is C= O or SO2, X is a covalent bond, R1 is alkyloxy, alkyloxyalkyl, Ar or NR9R10, wherein R9 and R10 each independently are hydrogen or Ar; or A=B and R1 together form a benzoxazolyl radical ; p is zero, R3 is benzyl optionally substituted with hydroxy, alkyl or alkyloxycarbonyl and R4 and R5 each are hydrogen. The invention also relates to processes for the preparation of the compounds according to the invention and their use in medicine, in particula r as selective non-peptide d-opioid agonists for use in the treatment of vario us pain conditions.

公开(公告)号：HK1043128A1

公开(公告)日：2002-09-06

申请号：HK02104999

申请日：2002-07-03

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： JANSSENS FRANS EDUARD ,  LEENAERTS JOSEPH ELISABETH

IPC: C07D20060101 ,  A61K20060101 ,  A61K31/438 ,  A61K31/55 ,  A61P20060101 ,  A61P11/06 ,  A61P17/00 ,  A61P17/04 ,  A61P27/14 ,  A61P27/16 ,  A61P37/00 ,  A61P37/08 ,  A61P43/00 ,  C07D471/20 ,  C07D487/20 ,  C07D495/22 ,  C07D498/20 ,  C07D519/00

Abstract: This invention concerns the compounds of formula or a prodrug, a N-oxide, an addition salt, a quaternary amine or a stereochemically isomeric form thereof wherein R 1 , R 2 , -A-B-, L, and n have the meaning given in the description. The invention relates to preparations and compositions of the present compounds and their use as medicines.

公开(公告)号：EE200100328A

公开(公告)日：2002-08-15

申请号：EEP200100328

申请日：1999-12-15

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： JANSSENS FRANS EDUARD ,  LEENAERTS JOSEPH ELISABETH

IPC: A61K31/438 ,  A61K31/55 ,  A61P11/06 ,  A61P17/00 ,  A61P17/04 ,  A61P27/14 ,  A61P27/16 ,  A61P37/00 ,  A61P37/08 ,  A61P43/00 ,  C07D471/20 ,  C07D487/20 ,  C07D495/22 ,  C07D498/20 ,  C07D519/00

Abstract: This invention concerns the compounds of formula or a prodrug, a N-oxide, an addition salt, a quaternary amine or a stereochemically isomeric form thereof wherein R 1 , R 2 , -A-B-, L, and n have the meaning given in the description. The invention relates to preparations and compositions of the present compounds and their use as medicines.

公开(公告)号：EE03773B1

公开(公告)日：2002-06-17

申请号：EE9800281

申请日：1997-03-11

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： JANSSENS FRANS EDUARD ,  LEENAERTS JOSEPH ELISABETH ,  SOMMEN FRANCOIS MARIA ,  SURLERAUX DOMINIQUE LOUIS NEST

IPC: A61K31/00 ,  A61K31/445 ,  A61K31/47 ,  A61K31/4738 ,  A61K31/4745 ,  A61K31/5365 ,  A61K31/55 ,  A61K31/553 ,  A61K45/00 ,  A61P31/00 ,  A61P31/06 ,  A61P33/00 ,  A61P33/02 ,  A61P33/04 ,  A61P33/06 ,  A61P35/00 ,  A61P35/02 ,  A61P43/00 ,  C07D471/04 ,  C07D487/04 ,  C07D487/14 ,  C07D491/147 ,  C07D495/14 ,  C07D498/04 ,  C07D498/14

Abstract: This invention concerns the compounds of formulathe N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein the dotted line is an optional bond; n is 1 or 2; R1 is hydrogen; halo; formyl; C1-4alkyl optionally substituted with hydroxy, C1-4alkyloxy, C1-4alkylcarbonyloxy, imidazolyl, thiazolyl or oxazolyl; or a radical of formula -X-COOR5, -X-CONR6R7 or -X-COR10 wherein -X- is a direct bond, C1-4alkanediyl or C2-6alkenediyl; R5 is hydrogen, C1-12alkyl, Ar, Het, C1-6alkyl substituted with C1-4alkyloxy, aryl or heteroaryl; R6 and R7 each independently are hydrogen or C1-4alkyl; R2 is hydrogen, halo, C1-4alkyl, hydroxyC1-4alkyl, C1-4alkyloxycarbonyl, carboxyl, formyl or phenyl; R3 is hydrogen, C1-4alkyl or C1-4alkyloxy; R4 is hydrogen, halo, C1-4alkyl, C1-4alkyloxy or haloC1-4alkyl; Z is -CH2-, -CH2-CH2-, -CH=CH-, -CHOH-CH2-, -O-CH2-, -C(=O)-CH2- or -C(=NOH)-CH2-; -A-B- is a bivalent radical; A1 is a direct bond, optionally substituted C1-6alkanediyl, C1-6alkanediyl-oxy-C1-6alkanediyl, carbonyl, C1-6alkanediylcarbonyl, optionally substituted C1-6alkanediyloxy; A2 is a direct bond or C1-6alkanediyl; and Q is aryl. Processes for preparing said products, formulations comprising said products and their use as a medicine are disclosed, in particular for inhibiting or reversing the effects of multidrug resistance.

公开(公告)号：PT843679E

公开(公告)日：2002-04-29

申请号：PT96944693

申请日：1996-12-20

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： ROOSBROECK YVES EMIEL MARIA VA ,  JANSSENS FRANS EDUARD ,  LEENAERTS JOSEPH ELISABETH

IPC: A61K31/00 ,  A61K31/395 ,  A61K31/435 ,  A61K31/4353 ,  A61K31/437 ,  A61K31/55 ,  A61K31/553 ,  A61P25/00 ,  A61P43/00 ,  C07D20060101 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D471/02 ,  C07D471/04 ,  C07D471/20 ,  C07D487/04 ,  C07D487/14 ,  C07D487/20 ,  C07D495/14 ,  C07D498/04

Abstract: This invention concerns the compounds of formulathe N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein n is 0, 1 or 2; m is 1 or 2, provided that if m is 2, then n is 1; =Q is =O or =NR3; X is a covalent bond or -O-, -S-, -NR3-; R1 is Ar1, Ar1C1-6alkyl or di(Ar1)C1-6alkyl, wherein each C1-6alkyl group is optionally substituted; R2 is Ar2, Ar2C1-6alkyl, Het or HetC1-6alkyl; R3 is hydrogen or C1-6alkyl; L is a piperidine derivative of formula (a-1) or a spiro piperidine derivative of formula (a-2); Ar1 is phenyl or substituted phenyl; Ar2 is naphtalenyl; phenyl or substituted phenyl; and Het is a monocyclic or bicyclic heterocycle; each monocyclic and bicyclic heterocycle may optionally be substituted on a carbon atom; as substance P antagonists; their preparation, compositions containing them and their use as a medicine.

公开(公告)号：HU0104779A2

公开(公告)日：2002-04-29

申请号：HU0104779

申请日：1999-12-15

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： JANSSENS FRANS EDUARD ,  LEENAERTS JOSEPH ELISABETH

IPC: A61K31/438 ,  A61K31/55 ,  A61P11/06 ,  A61P17/00 ,  A61P17/04 ,  A61P27/14 ,  A61P27/16 ,  A61P37/00 ,  A61P37/08 ,  A61P43/00 ,  C07D471/20 ,  C07D487/20 ,  C07D495/22 ,  C07D498/20 ,  C07D519/00

Abstract: This invention concerns the compounds of formula or a prodrug, a N-oxide, an addition salt, a quaternary amine or a stereochemically isomeric form thereof wherein R 1 , R 2 , -A-B-, L, and n have the meaning given in the description. The invention relates to preparations and compositions of the present compounds and their use as medicines.

公开(公告)号：DK0869955T3

公开(公告)日：2002-02-18

申请号：DK96944686

申请日：1996-12-20

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： JANSSENS FRANS EDUARD ,  SOMMEN FRANCOIS MARIA ,  SURLERRAUX DOMINIQUE LOUIS NES ,  LEENAERTS JOSEPH ELISABETH

IPC: A61K31/00 ,  A61K31/415 ,  A61K31/435 ,  A61K31/4418 ,  A61K31/4427 ,  A61K31/443 ,  A61K31/4433 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/445 ,  A61K31/4465 ,  A61K31/4523 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/495 ,  A61K31/4965 ,  A61K31/497 ,  A61K31/498 ,  A61K31/55 ,  A61P1/00 ,  A61P9/00 ,  A61P11/00 ,  A61P17/00 ,  A61P25/00 ,  A61P25/04 ,  A61P29/00 ,  A61P35/00 ,  A61P37/00 ,  A61P43/00 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04

Abstract: N-heterocyclic compounds of formula (I), and their N-oxides, salts and isomers, are new. n = 0, 1 or 2; m = 1 or 2, provided that when m is 2, then n is 1; X = a bond, O, S or NR3; Q = O or NR3; R1 = Ar1, Ar1(1-6C alkyl) or di(Ar1)(1-6C alkyl), where the 1-6C alkyl groups are optionally substituted by OH, TO, oxo or a ketalised oxo substituent of formula OCH2CH2O or OCH2CH2CH2O; R2 = Ar2, Ar2(1-6C alkyl), Het or Het(1-6C alkyl); L = a group of formula (i) or (ii); p = 0, 1 or 2; Y, depending on whether the optional second bond is present or not, is (i) a bivalent radical of formula CH2, CH(OH), C(O), O, S, SO, SO2, NR3, CH2NR3 or CONR3, or (ii) a trivalent radical of formula CH; A=B is a bivalent radical of formula CH=CH, N=CH or CH=N; R3 = H or R; R4 = H, R, 3-7C cycloalkyl, Alk-R7 or Alk-Z-R8; Alk = 1-6C alkanediyl; Z = O, S or NR3; R7 = Ph (optionally substituted by 1-2 halo, R or RO); furanyl (optionally substituted by 1-2 R or hydroxy(1-6C alkyl)); thienyl (optionally substituted by 1-2 halo or R); oxazolyl, thiazolyl or pyridinyl (all optionally substituted by 1-2 R); R8 = R (optionally substituted by OH, COOH or COOR); R5 = H, halo, OH or RO; R6 = H, R or Ar1(1-6 alkyl); Ar1 = Ph (optionally substituted by 1-3 halo, T, T', CN, CONH2, TO or T'O); Ar2 = naphthalenyl, or Ph (optionally substituted by 1-3 OH, halo, CN, NO2, NH2, NHT, N(T)2, T, T', TO, T'O, COOH, COOT, CONH2, CONHT or CON(T)2); Het = pyrrolyl, pyrazolyl, imidazolyl, furanyl, thienyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, quinolinyl, quinoxalinyl, indolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzofuranyl or benzothienyl (all optionally substituted on carbon by 1-2 halo, T or mono-, di- or tri(halo)methyl); T, T', R, = 1-4C alkyl, halo(1-4C alkyl), 1-6C alkyl respectively.

公开(公告)号：HRP960507B1

公开(公告)日：2001-08-31

申请号：HRP960507

申请日：1996-10-30

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： JANSSENS FRANS EDUARD ,  SOMMEN FRANCOIS MARIA ,  SURLEAUX DOMINIQUE LOUIS MESTO ,  LEENAERTS JOSEPH ELISABETH ,  VAN ROOSBROECK YVES EMIEL MARI

IPC: C07D401/04 ,  A61K31/00 ,  A61K31/495 ,  A61K31/496 ,  A61K31/4965 ,  A61K31/497 ,  A61K31/498 ,  A61P1/08 ,  A61P23/00 ,  A61P29/00 ,  A61P37/02 ,  A61P37/08 ,  A61P43/00 ,  C07D211/58 ,  C07D401/12 ,  C07D401/14 ,  C07D405/06 ,  C07D405/12 ,  C07D405/14 ,  C07D409/06 ,  C07D409/14 ,  C07D413/06 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D471/14

Abstract: This invention concerns the compounds of formulathe N-oxide forms, the pharmaceutically acceptable addition salts and the stereoisomeric forms thereof, as substance-P antagonists; their preparation, compositions containing them and their use as a medicine.

公开(公告)号：EA001374B1

公开(公告)日：2001-02-26

申请号：EA199800603

申请日：1996-12-20

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： JANSSENS FRANS EDUARD ,  LEENAERTS JOSEPH ELISABETH ,  VAN ROOSBROECK YVES EMIEL

IPC: A61K31/00 ,  A61K31/395 ,  A61K31/435 ,  A61K31/4353 ,  A61K31/437 ,  A61K31/55 ,  A61K31/553 ,  A61P25/00 ,  A61P43/00 ,  C07D20060101 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D471/02 ,  C07D471/04 ,  C07D471/20 ,  C07D487/04 ,  C07D487/14 ,  C07D487/20 ,  C07D495/14 ,  C07D498/04 ,  A61P1/04 ,  A61P11/08 ,  A61P13/10 ,  A61P17/04 ,  A61P17/06 ,  A61P19/02 ,  A61P23/00 ,  A61P31/16 ,  A61P31/22 ,  A61P37/08

Abstract: Настоящееизобретениекасаетсясоединенийформулы (I), их N-оксидныхформфармацевтическиприемлемыхсолейприсоединенияи стереохимическиизомерныхформ, где n равно 0, 1 или 2; m равно 1 или 2, приусловии, чтоесли m равно 2, то n равно 1; =Q является =O или =NR; X являетсяковалентнойсвязьюили -О-, -S-, -NR-; Rявляется Ar, ArCалкиломилиди(Ar)Cалкилом, гдекаждая Cалкильнаягруппапроизвольнозамещена; Rявляется Ar, ArCалкилом; Het или HetCалкилом; Rявляетсяводородомили Cалкилом; L являетсяпиперидиновымпроизводнымформулы (а-1) илиспиропиперидиновымпроизводнымформулы (а-2); Arявляетсяфениломилизамещеннымфенилом; Arявляетсянафталинилом; фениломилизамещеннымфенилом; и Het являетсямоноциклическимилибициклическимгетероциклом; каждыймоноциклическийилибициклическийгетероциклможетбытьнеобязательнозамещенпоатомууглерода; вкачествеантагонистоввеществаР; ихполучения, содержащихихкомпозицийи ихпримененияв качествелекарственныхпрепаратов.

公开(公告)号：SI0862566T1

公开(公告)日：2000-04-30

申请号：SI9630141

申请日：1996-10-25

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： JANSSENS FRANS EDUARD ,  SOMMEN FRANCOIS MARIA ,  SURLERAUX DOMINIQUE LOUIS NEST ,  LEENAERTS JOSEPH ELISABETH ,  VAN ROOSBROECK YVES EMIEL MARI

IPC: C07D401/04 ,  A61K31/00 ,  A61K31/495 ,  A61K31/496 ,  A61K31/4965 ,  A61K31/497 ,  A61K31/498 ,  A61P1/08 ,  A61P23/00 ,  A61P29/00 ,  A61P37/02 ,  A61P37/08 ,  A61P43/00 ,  C07D211/58 ,  C07D401/12 ,  C07D401/14 ,  C07D405/06 ,  C07D405/12 ,  C07D405/14 ,  C07D409/06 ,  C07D409/14 ,  C07D413/06 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D471/14

Abstract: This invention concerns the compounds of formulathe N-oxide forms, the pharmaceutically acceptable addition salts and the stereoisomeric forms thereof, as substance-P antagonists; their preparation, compositions containing them and their use as a medicine.