公开(公告)号：WO02100862A3

公开(公告)日：2003-02-27

申请号：PCT/EP0206576

申请日：2002-06-11

Applicant: JANSSEN PHARMACEUTICA NV ,  JANSSENS FRANS EDUARD ,  LEENAERTS JOSEPH ELISABETH ,  VAN ROSSEM KOENRAAD ARTHUR ,  ALCAZAR-VACA MANUEL JESUS ,  MARTINEZ-JIMENEZ PEDRO ,  BARTOLOME-NEBREDA JOSE MANUEL ,  GOMEZ-SANCHEZ ANTONIO ,  FERNANDEZ-GADEA FRANCISCO JAVI ,  VAN REEMPTS JOS

Inventor： JANSSENS FRANS EDUARD ,  LEENAERTS JOSEPH ELISABETH ,  VAN ROSSEM KOENRAAD ARTHUR ,  ALCAZAR-VACA MANUEL JESUS ,  MARTINEZ-JIMENEZ PEDRO ,  BARTOLOME-NEBREDA JOSE MANUEL ,  GOMEZ-SANCHEZ ANTONIO ,  FERNANDEZ-GADEA FRANCISCO JAVI ,  VAN REEMPTS JOS

IPC: A61K9/10 ,  A61K31/00 ,  A61K31/519 ,  A61K31/55 ,  A61P3/00 ,  A61P7/10 ,  A61P9/10 ,  A61P25/00 ,  A61P43/00 ,  C07D471/04 ,  C07D487/04 ,  C07D487/14 ,  C07D495/04 ,  C07D519/00

CPC classification number: C07D487/04 ,  C07D471/04

Abstract: The invention concerns novel substituted tetracyclic imidazole derivatives useful for the treatment of elevated intracranial pressure (ICP) and/or secondary ischaemia, in particular caused by brain injury, more in particular caused by traumatic (TBI) and non-traumatic brain injury, processes for their preparation, pharmaceutical compositions comprising them and their use as a medicine. The novel compounds comprise compounds according to the general Formula (I), the pharmaceutically acceptable acid or base addition salts thereof, the stereochemically isomeric forms thereof and the N -oxide form thereof. In particular, the preferred compound is 3-[2-[4-(11,12-dihydro- 6 H - benzimidazo[2,1 -b][3]benzazepin-6-yl) -2-(phenylmethyl)- 1-piperidinyl]ethyl] -2,10-dimethyl pyrimido[1, 2- a ]benzimidazol- 4(10 H )-one, the pharmaceutically acceptable acid or base addition salts thereof, the stereochemically isomeric forms thereof and the N -oxide form thereof.

Abstract translation: 本发明涉及可用于治疗升高的颅内压（ICP）和/或继发性缺血的新型取代的四环咪唑衍生物，特别是由脑损伤引起的，特别是由创伤性（TBI）和非创伤性脑损伤引起的 其制备方法，包含它们的药物组合物及其作为药物的用途。 新化合物包括根据通式（I）的化合物，其药学上可接受的酸或碱加成盐，其立体化学异构形式和其N-氧化物形式。 特别地，优选的化合物是3- [2- [4-（11,12-二氢-6H-苯并咪唑并[2,1-b] [3]苯并氮杂-6-基）-2-（苯基甲基） - 哌啶基]乙基] -2,10-二甲基嘧啶并[1,2-a]苯并咪唑-4（10H） - 酮，其药学上可接受的酸或碱加成盐，其立体化学异构形式和N-氧化物形式 它们。

公开(公告)号：WO2006061392A3

公开(公告)日：2006-11-02

申请号：PCT/EP2005056544

申请日：2005-12-06

Applicant: JANSSEN PHARMACEUTICA NV ,  CID-NUNEZ JOSE MARIA ,  MEGENS ANTONIUS ADRIANUS HENDR ,  TRABANCO-SUAREZ ANDRES AVELINO ,  KOUKNI MOHAMED ,  HOORNAERT GEORGES JOSEPH CORNE ,  COMPERNOLLE FRANS JOSEF CORNEL ,  KOZLECKI TOMASZ ,  MAO HUA ,  JHA SUSHIL CHANDRA ,  FERNANDEZ-GADEA FRANCISCO JAVI

Inventor： CID-NUNEZ JOSE MARIA ,  MEGENS ANTONIUS ADRIANUS HENDR ,  TRABANCO-SUAREZ ANDRES AVELINO ,  KOUKNI MOHAMED ,  HOORNAERT GEORGES JOSEPH CORNE ,  COMPERNOLLE FRANS JOSEF CORNEL ,  KOZLECKI TOMASZ ,  MAO HUA ,  JHA SUSHIL CHANDRA ,  FERNANDEZ-GADEA FRANCISCO JAVI

IPC: C07D209/70 ,  A61K31/343 ,  A61K31/352 ,  A61K31/381 ,  A61K31/403 ,  A61K31/407 ,  A61K31/4188 ,  A61K31/496 ,  A61K31/4985 ,  C07D221/18 ,  C07D307/93 ,  C07D311/94 ,  C07D333/80 ,  C07D487/04 ,  C07D491/044

CPC classification number: C07D333/80 ,  C07D209/70 ,  C07D221/18 ,  C07D307/93 ,  C07D311/94 ,  C07D487/04 ,  C07D491/04

Abstract: This invention concerns novel substituted tetracyclic tetrahydrofuran, pyrrolidine and tetrahydrothiophene derivatives with binding affinities towards serotonin receptors, in particular 5-HT 2A and 5-HT 2C receptors, and towards dopamine receptors, in particular dopamine D2 receptors and with norepinephrine reuptake inhibition properties, pharmaceutical compositions comprising the compounds according to the invention, the use thereof as a medicine, in particular for the prevention and/or treatment of a range of psychiatric and neurological disorders, in particular certain psychotic, cardiovascular and gastrokinetic disorders and processes for their production. The compounds according to the invention can be represented by general Formula (I) and comprises also the pharmaceutically acceptable acid or base addition salts thereof, the stereochemically isomeric forms thereof, the N-oxide form thereof and prodrugs thereof, wherein all substituents are defined as in Claim 1.

Abstract translation: 本发明涉及对5-羟色胺受体，特别是5-HT 2A和5-HT 2C受体具有结合亲和力的新型取代四环四氢呋喃，吡咯烷和四氢噻吩衍生物，并且涉及多巴胺受体 特别是多巴胺D2受体和去甲肾上腺素再摄取抑制性质，包含根据本发明的化合物的药物组合物，其作为药物的用途，特别是用于预防和/或治疗一系列精神和神经障碍，特别是 某些精神病，心血管和胃肠功能障碍及其生产过程。 根据本发明的化合物可以由通式（I）表示，并且还包括其药学上可接受的酸或碱加成盐，其立体化学异构形式，其N-氧化物形式及其前药，其中所有取代基定义为 在权利要求1中。

公开(公告)号：PT1832287E

公开(公告)日：2009-05-05

申请号：PT07107669

申请日：2002-11-22

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： JANSSENS FRANS EDUARD ,  LEENAERTS JOSEPH ELISABETH ,  TEGTMEIER FRANK ,  ROSSEM KOENRAAD ARTHUR VAN ,  REEMPTS JOZEF LEO HENRI VAN ,  ALCAZAR-VACA MANUEL JESUS ,  MARTINEZ-JIMENEZ PEDRO ,  BARTOLOME-NEBREDA JOSE MANUEL ,  FERNANDEZ-GADEA FRANCISCO JAVI

IPC: A61P9/10 ,  C07D487/04 ,  A61K31/415 ,  A61K31/425 ,  A61K31/513 ,  A61K31/517 ,  A61K31/519 ,  A61K31/55 ,  A61P1/04 ,  A61P29/00 ,  A61P37/02 ,  A61P37/06 ,  A61P37/08 ,  C07D471/00 ,  C07D471/04 ,  C07D487/00 ,  C07D519/00

公开(公告)号：SI1451196T1

公开(公告)日：2007-12-31

申请号：SI200230617

申请日：2002-11-22

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： TEGTMEIER FRANK ,  JANSSENS FRANS EDUARD ,  LEENAERTS JOSEPH ELISABETH ,  VAN ROSSEM KOENRAAD ARTHUR ,  ALCAZAR-VACA MANUEL JESUS JANS ,  MARTINEZ-JIMENEZ PEDRO JANSSEN ,  BARTOLOME-NEBREDA JOSE MANUEL ,  GOMEZ-SANCHEZ ANTONIO JANSSEN- ,  FERNANDEZ-GADEA FRANCISCO JAVI ,  VAN REEMPTS JOZEF LEO HENRI

IPC: C07D487/04 ,  C07D519/00 ,  A61K31/00 ,  A61K31/415 ,  A61K31/425 ,  A61K31/513 ,  A61K31/517 ,  A61K31/519 ,  A61K31/55 ,  A61P1/04 ,  A61P9/00 ,  A61P9/10 ,  A61P29/00 ,  A61P37/00 ,  A61P37/02 ,  A61P37/06 ,  A61P37/08 ,  C07D471/00 ,  C07D471/04 ,  C07D487/00

公开(公告)号：AU2002244717B2

公开(公告)日：2007-07-19

申请号：AU2002244717

申请日：2002-02-13

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： PASTOR-FERNANDEZ JOAQUIN ,  STECKLER THOMAS HORST WOLFGANG ,  HEYLEN GODELIEVE IRMA CHRISTIN ,  ANDRES-GIL JOSE IGNACIO ,  ALCAZAR-VACA MANUEL JESUS ,  MEGENS ANTONIUS ADRIANUS HENDR ,  BAKKER MARGARETHA HENRICA MARI ,  LANGLOIS XAVIER JEAN MICHEL ,  CID-NUNEZ JOSE MARIA ,  FERNANDEZ-GADEA FRANCISCO JAVI

IPC: C07D498/04 ,  A61K31/454 ,  A61K31/495 ,  A61K31/496 ,  A61K31/538 ,  A61P3/04 ,  A61P25/00 ,  A61P25/18 ,  A61P25/22 ,  A61P25/24 ,  C07D261/20 ,  C07D498/14 ,  C07D519/00

Abstract: The invention concerns substituted isoxazolines derivatives according to Formula (I): wherein X=CH?2#191, N-R 7 , S or O, R 1 , R 2 and R 3 are certain specific substituents, Pir is an optionally substituted piperidyl or piperazyl radical and R3 represents an optionally substituted aromatic homocyclic or heterocyclic ring system including a partially or completely hydrogenated hydrocarbon chain of maximum 6 atoms long with which the ring system is attached to the Pir radical and which may contain one or more heteroatoms selected from the group of O, N and S; a process for their preparation, pharmaceutical compositions comprising them and their use as a medicine, in particular for the treatment of depression and/of anxiety and disorders of body weight. The compounds according to the invention have surprisingly been shown to have a serotonine (5-HT) reuptake inhibitor activity in combination with additional alpha2-adrenoceptor antagonist activity and show a strong anti-depressant activity without being sedative. Compounds according to the invention arc also suitable for treating patients with anxiety disorders and disorders of body weight. The invention also relates to novel combination of substituted isoxazolines derivatives having anti-depressant activity and/or anxiolytic activity and/or body weight control activity with antidepressants, anxiolytics and/or antipsychotics to improve efficacy and/or onset of action

公开(公告)号：CZ297474B6

公开(公告)日：2006-12-13

申请号：CZ102899

申请日：1997-09-24

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： FREYNE EDDY JEAN EDGARD ,  FERNANDEZ-GADEA FRANCISCO JAVI ,  ANDRES-GIL JOSU IGNACIO

IPC: C07D233/44 ,  C07D405/12 ,  A61K31/00 ,  A61K31/415 ,  A61K31/4164 ,  A61K31/4168 ,  A61K31/4178 ,  A61P11/00 ,  A61P11/06 ,  A61P29/00 ,  A61P37/00 ,  A61P37/08 ,  C07D233/48 ,  C07D233/88

Abstract: Resení se týká 2-kyaniminoimidazolových derivátu obecného vzorce I, jejich N-oxidové formy, farmaceuticky prijatelných adicních solí a stereochemickyizomerních forem, kde R.sup.1.n. a R.sup.2.n. jsou nezávisle vodík; alkyl s 1 az 6 atomy uhlíku; difluormethyl; trifluormethyl; cykloalkyl se 3 az 6 atomy uhlíku; 5-, 6- nebo 7-clenný heterocykl obsahující jeden nebo dva atomy vybrané z kyslíku, síry nebo dusíku; indanyl; 6,7-dihydro-5H-cyklopentypyridinyl; bicyklo[2.2.1]-2-heptenyl; bicyklo[2.2.1]heptanyl; alkylsulfonyl s 1 az 6 atomy uhlíku; arylsulfonyl; nebo substituovaný alkyl s 1 az 10 atomy uhlíku; R.sup.3.n. je vodík, halo nebo alkoxy s1 az 6 atomy uhlíku; R.sup.4.n. je vodík; halo; alkyl s 1 az 6 atomy uhlíku; trifluormethyl; cykloalkyl se 3 az 6 atomy uhlíku; karboxyl; alkyloxykarbonyl s 1 az 4 atomy uhlíku v alkylu; alkylaminokarbonyl se 3 az 6 atomy uhlíku v cykloalkylu; aryl;Het.sup.1.n.; nebo substituovaný alkyl s 1 az 6 atomy uhlíku; nebo R.sup.4.n. je -O-R.sup.7.n. nebo-NH-R.sup.8.n.; R.sup.5.n. je vodík, halo, hydroxy, alkyl s 1 az 6 atomy uhlíku nebo alkyloxy s 1 az 6 atomy uhlíku; R.sup.6.n. je vodík nebo alkyl s1 az 4 atomy uhlíku; nebo R.sup.4.n. a R.sup.6.n.nebo R.sup.4.n. a R.sup.5.n. spolecne mohou tvorit bivalentní skupinu; -A-B- je -CR.sup.10.n.=R.sup.11.n.- nebo -CHR.sup.10.n.-CHR.sup.11.n.-; L je vodík; alkyl s 1 az 6 atomy uhlíku; alkylkarbonyl s1 az 6 atomy uhlíku v alkylu; alkyloxykarbonyl s 1 az 6 atomy uhlíku v alkylu; substituovaný alkyl s 1 az 6 atomy uhlíku; alkenyl se 3 az 6 atomy uhlíku; substituovaný alkenyl se 3 az 6 atomy uhlíku;piperidinyl; substituovaný piperidinyl; alkylsulfonyl s 1 az 6 atomy uhlík

公开(公告)号：CA2604165A1

公开(公告)日：2006-11-30

申请号：CA2604165

申请日：2006-05-24

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： FERNANDEZ-GADEA FRANCISCO JAVI ,  CID-NUNEZ JOSE MARIA ,  MAO HUA ,  JHA SUSHIL CHANDRA ,  COMPERNOLLE FRANS JOSEF CORNEL ,  TRABANCO-SUAREZ ANDRES AVELINO ,  KOZLECKI TOMASZ ,  MEGENS ANTONIUS ADRIANUS HENDR ,  HOORNAERT GEORGES JOSEPH CORNE ,  KOUKNI MOHAMED

IPC: C07D487/04 ,  A61K31/403 ,  A61K31/407 ,  A61P25/00 ,  C07D209/94 ,  C07D221/18 ,  C07D307/93 ,  C07D311/94 ,  C07D333/80 ,  C07D491/04

Abstract: This invention concerns novel substituted tetracyclic tetrahydrofuran, pyrrolidine and tetrahydrothiophene derivatives with binding affinities towards serotonin receptors, in particular 5-HT2A and 5-HT2C receptors, and towards dopamine receptors, in particular dopamine D2 receptors and with norepinephrine reuptake inhibition properties, pharmaceutical compositions comprising the compounds according to the invention, the use thereof as a medicine, in particular for the prevention and/or treatment of a range of psychiatric and neurological disorders, in particular certain psychotic, cardiovascular and gastrokinetic disorders and processes for their productio n. The compounds according to the invention can be represented by general Formu la (I), and comprises also the pharmaceutically acceptable acid or base additio n salts thereof, the stereochemically isomeric forms thereof, the N-oxide form thereof and prodrugs thereof, wherein all substituents are defined as in Cla im 1.

公开(公告)号：AU2006251166A1

公开(公告)日：2006-11-30

申请号：AU2006251166

申请日：2006-05-24

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： MAO HUA ,  KOZLECKI TOMASZ ,  HOORNAERT GEORGES JOSEPH CORNE ,  TRABANCO-SUAREZ ANDRES AVELINO ,  CID-NUNEZ JOSE MARIA ,  JHA SUSHIL CHANDRA ,  MEGENS ANTONIUS ADRIANUS HENDR ,  FERNANDEZ-GADEA FRANCISCO JAVI ,  COMPERNOLLE FRANS JOSEF CORNEL ,  KOUKNI MOHAMED

IPC: C07D487/04 ,  A61K31/403 ,  A61K31/407 ,  A61P25/00 ,  C07D209/94 ,  C07D221/18 ,  C07D307/93 ,  C07D311/94 ,  C07D333/80 ,  C07D491/04

Abstract: This invention concerns novel substituted tetracyclic tetrahydrofuran, pyrrolidine and tetrahydrothiophene derivatives with binding affinities towards serotonin receptors, in particular 5-HT2A and 5-HT2C receptors, and towards dopamine receptors, in particular dopamine D2 receptors and with norepinephrine reuptake inhibition properties, pharmaceutical compositions comprising the compounds according to the invention, the use thereof as a medicine, in particular for the prevention and/or treatment of a range of psychiatric and neurological disorders, in particular certain psychotic, cardiovascular and gastrokinetic disorders and processes for their production. The compounds according to the invention can be represented by general Formula (I) and comprises also the pharmaceutically acceptable acid or base addition salts thereof, the stereochemically isomeric forms thereof, the N-oxide form thereof and prodrugs thereof, wherein all substituents are defined as in Claim 1.

公开(公告)号：CA2606774A1

公开(公告)日：2006-11-23

申请号：CA2606774

申请日：2006-05-17

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： TRABANCO-SUAREZ ANDRES AVELINO ,  CID-NUNEZ JOSE MARIA ,  MEGENS ANTONIUS ADRIANUS HENDR ,  FERNANDEZ-GADEA FRANCISCO JAVI ,  ANDRES-GIL JOSE IGNACIO

IPC: C07D405/06 ,  C07D493/04 ,  C07D495/04

Abstract: This invention concerns novel tetracyclic tetrahydrofuran derivatives containing a cyclic amine side chain with binding affinities towards serotonin receptors, in particular 5-HT 2A and 5-HT 2C receptors, and towards dopamine receptors, in particular dopamine D 2 receptors, pharmaceutical compositions comprising the compounds according to the invention, the use thereof as a medicine, in particular for the prevention and/or treatment of a range of psychiatric and neurological disorders, in particular certain psychotic, cardiovascular and gastrokinetic disorders and processes for their production. The compounds according to the invention can be represented by general Formula (I) and comprises also a pharmaceutically acceptable acid or base addition salt thereof, a stereochemically isomeric form thereof, an N-oxide form thereof, and a quaternary ammonium salt thereof, wherein all substituents are defined as in claim 1.

公开(公告)号：HU225161B1

公开(公告)日：2006-07-28

申请号：HU0003748

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: C07D307/93 ,  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 ,  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.