公开(公告)号：WO03048147A2

公开(公告)日：2003-06-12

申请号：PCT/EP0213561

申请日：2002-12-02

Applicant: JANSSEN PHARMACEUTICA NV ,  MAO HUA ,  KOZLECKI TOMASZ ,  COMPERNOLLE FRANS JOSEF CORNEL ,  HOORNAERT GEORGES JOSEPH CORNE

Inventor： MAO HUA ,  KOZLECKI TOMASZ ,  COMPERNOLLE FRANS JOSEF CORNEL ,  HOORNAERT GEORGES JOSEPH CORNE

IPC: A61K31/34 ,  A61K31/343 ,  A61P25/00 ,  A61P25/06 ,  A61P25/18 ,  A61P25/22 ,  A61P25/24 ,  A61P25/30 ,  C07D307/93

CPC classification number: C07D307/93

Abstract: The present invention concerns a process for preparing each of the 4 individual diastereomers of formula (I) in stereochemically pure form from a single enantiomerically pure precursor. The tetracyclic ringsystem having cis-fused five and seven membered rings is formed in a base-catalysed cyclization reaction. The invention further relates to the thus obtained cis-fused tetracyclic alcohol intermediates and methanamine end-products, and the methanamine end-products for use as a medicine, in particular as CNS active medicines.

Abstract translation: 本发明涉及从单一对映异构体纯的前体以立体化学纯的形式制备式（I）的4种单独的非对映异构体的方法。 在碱催化的环化反应中形成具有顺式稠合的五元和七元环的四环环系。 本发明还涉及由此获得的顺式稠合四环醇中间体和甲胺终产物，以及用作药物的甲胺最终产物，特别是CNS活性药物。

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：AU2011202995B2

公开(公告)日：2012-02-02

申请号：AU2011202995

申请日：2011-06-21

Applicant: JANSSEN PHARMACEUTICA NV

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

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

Abstract: This invention concerns novel substituted tetracyclic tetrahydrofuran, pyrrolidine and tetrahydrothiophene derivatives with binding affinities towards serotonin receptors, in particular 5-HT2A and 5-HT 2c receptors, and towards dopamine receptors, in particular dopamine D2 receptors and with norepinephrine reuptake inhibition 10 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 (1) (R9i A B (R9j 20 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：BRPI0611408A2

公开(公告)日：2010-09-08

申请号：BRPI0611408

申请日：2006-05-24

Applicant: JANSSEN PHARMACEUTICA NV

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

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：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：NZ532806A

公开(公告)日：2006-01-27

申请号：NZ53280602

申请日：2002-12-02

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： LANG YOLANDE LYDIA ,  MEDAER BART PETRUS ANNA MARIA ,  HOORNAERT GEORGES JOSEPH CORNE ,  BROSSETTE THIERRY ,  COMPERNOLLE FRANS JOSEF CORNEL ,  GUILLAUME MICHEL JOSEPH MAURIC ,  MAO HUA ,  KOZLECKI TOMASZ

IPC: A61K31/34 ,  A61K31/343 ,  A61P25/06 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/30 ,  C07D307/93

Abstract: A process for preparing each individual diastereoisomer of formula (I) wherein the substituents on carbon atoms 3a and 12b have the trans configuration, the substituent on carbon atom 2 may have the R or the S configuration, comprising the step of cyclizing a compound of formula (II) wherein R represents C1-3 alkylcarbonyl; OR1 represents a leaving group and the substituents -OR and -CH2-CHOH-CH2OR1 have the cis configuration, in a reaction inert solvent in the presence of an acid.

公开(公告)号：HK1076461A1

公开(公告)日：2006-01-20

申请号：HK05108415

申请日：2005-09-23

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： LANG YOLANDE LYDIA ,  MEDAER BART PETRUS ANNA MARIA ,  HOORNAERT GEORGES JOSEPH CORNE ,  BROSSETTE THIERRY ,  COMPERNOLLE FRANS JOSEF CORNEL ,  GUILLAUME MICHEL JOSEPH MAURIC ,  MAO HUA ,  KOZLECKI TOMASZ

IPC: C07D20060101 ,  A61K20060101 ,  A61K31/34 ,  A61K31/343 ,  A61P25/06 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/30 ,  C07D307/93

Abstract: The present invention concerns processes for the preparation of each of the 4 diastereomers of formula (I) in stereochemically pure form from either of two enantiomerically pure precursors. The tetracyclic ringsystem having trans-fused five and seven membered rings is formed in an acid-catalysed cyclization reaction. The invention further relates to the thus obtained cis-fused tetracyclic alcohol intermediates, the methanamine end-products, the methanamine end-products for use as a medicine, in particular as CNS active medicines.

公开(公告)号：PL369585A1

公开(公告)日：2005-05-02

申请号：PL36958502

申请日：2002-12-02

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： LANG YOLANDE LYDIA ,  MEDAER BART PETRUS ANNA MARIA ,  HOORNAERT GEORGES JOSEPH CORNE ,  BROSSETTE THIERRY ,  COMPERNOLLE FRANS JOSEF CORNEL ,  GUILLAUME MICHEL JOSEPH MAURIC ,  MAO HUA ,  KOZLECKI TOMASZ

IPC: A61K31/34 ,  A61K31/343 ,  A61P25/06 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/30 ,  C07D307/93

Abstract: The present invention concerns processes for the preparation of each of the 4 diastereomers of formula (I) in stereochemically pure form from either of two enantiomerically pure precursors. The tetracyclic ringsystem having trans-fused five and seven membered rings is formed in an acid-catalysed cyclization reaction. The invention further relates to the thus obtained cis-fused tetracyclic alcohol intermediates, the methanamine end-products, the methanamine end-products for use as a medicine, in particular as CNS active medicines.

公开(公告)号：CA2588760C

公开(公告)日：2014-05-13

申请号：CA2588760

申请日：2005-12-06

Applicant: JANSSEN PHARMACEUTICA NV

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

IPC: C07D209/70 ,  A61K31/352 ,  A61K31/381 ,  A61K31/403 ,  A61K31/407 ,  A61K31/435 ,  A61P25/00 ,  C07D221/18 ,  C07D311/94 ,  C07D333/80 ,  C07D403/06 ,  C07D413/06 ,  C07D487/04 ,  C07D491/044

Abstract: This invention concerns 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. (see formula I)