公开(公告)号：BR0317658A

公开(公告)日：2005-12-06

申请号：BR0317658

申请日：2003-12-17

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： JANSSENS FRANS EDUARD ,  SOMMEN FRANCOIS MARIA ,  BOECK BENOIT CHRISTIAN ALBERT ,  LEENAERTS JOSEPH ELISABETH

IPC: A61K31/454 ,  A61P25/00 ,  C07D401/12 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D498/14

Abstract: This invention concerns substituted I-piperidin-4-yl-4-pyrrolidin-3-yl-piperazine derivatives having neurokinin antagonistic activity, in particular NK1 antagonistic activity, a combined NK1/NK3 antagonistic activity and a combined NK1/NK2/NK3 antagonistic activity, their preparation, compositions comprising them and their use as a medicine, in particular for the treatment of schizophrenia, anxiety, depression, emesis and IBS. 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. In view of their capability to antagonize the actions of tachykinins by blocking the neurokinin receptors, and in particular antagonizing the actions of substance P and Neurokinin B by blocking the NK1, NK2 and NK3 receptors, the compounds according to the invention are useful as a medicine, in particular in the prophylactic and therapeutic treatment of tachykinin-mediated conditions, such as, for instance CNS disorders, in particular schizoaffective disorders, depression, anxiety disorders, stress-related disorders, sleep disorders, cognitive disorders, personality disorders, eating disorders, neurodegenerative diseases, addiction disorders, mood disorders, sexual dysfunction, pain and other CNS-related conditions; inflammation; allergic disorders; emesis; gastrointestinal disorders, in particular irritable bowel syndrome (IBS); skin disorders; vasospastic diseases; fibrosing and collagen diseases; disorders related to immune enhancement or suppression and rheumatic diseases and body weight control.

公开(公告)号：ES2242443T3

公开(公告)日：2005-11-01

申请号：ES99964625

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: Compuesto de **fórmula** un N-óxido, una sal de adición, una amina cuaternaria o una forma estereoquímicamente isomérica del mismo, en los que: R1 es hidrógeno, alquilo C1-6, halógeno, formilo, carboxilo, (alquiloxi C1-6)carbonilo, (alquil C1-6)carbonilo, N(R3R4)C(=O)-, N(R3R4)C(=O)N(R5)-, etenilo sustituido con carboxilo o (alquiloxi C1-6)carbonilo, o alquilo C1-6 sustituido con hidroxilo, carboxilo, alquiloxilo C1-6, (alquiloxi C1-6)carbonilo, N(R3R4)C(=O)-, (alquil C1- 6)C(=O)N(R5)-, (alquil C1-6)S(=O)2N(R5)-o N(R3R4)C(=O)N(R5)-; en donde cada R3 y cada R4 son independientemente hidrógeno o alquilo C1-4; R5 es hidrógeno o hidroxilo; R2 es hidrógeno, alquilo C1-6, hidroxi(alquilo C1-6), (alquiloxi C1-6)alquilo C1-6, N(R3R4)C(=O)-, arilo o halógeno; n es 1 ó 2; -A-B- representa un radical divalente de fórmula -Y-CH=CH- (a-1); -CH=CH-Y- (a-2); ó -CH=CH-CH=CH- (a-3).

公开(公告)号：DK1144411T3

公开(公告)日：2005-09-19

申请号：DK99964625

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：MXPA05006888A

公开(公告)日：2005-08-16

申请号：MXPA05006888

申请日：2003-12-17

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： LEENAERTS JOSEPH ELISABETH

IPC: A61P25/00 ,  A61P29/00 ,  C07D211/58 ,  C07D211/96 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D513/04 ,  A61K31/496

Abstract: La presente invencion se refiere a derivados de 1-piperidin-3-il-4-piperidin-4-il-piperazina sustituidos que tienen actividad antagonista de neuroquinina, en particular actividad antagonista de NK1, actividad antagonista NK1/NK3 combinada y actividad antagonista NK1/NK2/NK3 combinada, a su preparacion, a las composiciones que las comprenden y a su uso como medicamentos, en particular para el tratamiento de la esquizofrenia, emesis, ansiedad y depresion, sindrome de intestino irritable (lBS), perturbaciones del ritmo circadiano, dolor visceral, inflamacion neurogenica, asma, perturbaciones de miccion tales como incontinencia urinaria y nocicepcion; los compuestos de conformidad con la presente invencion se pueden representar mediante la Formula general (I) y comprenden tambien las sales de adicion de acidos o bases farmaceuticamente aceptables de los mismos, las formas estereoquimicamente isomericas de los mismos, la forma de N-oxido de los mismos y los profarmacos de los mismos, en donde todos los sustituyentes se definen en la Reivindicacion 1; en vista de su capacidad para antagonizar las acciones de las taquiquininas bloqueando los receptores de neuroquininas, y particularmente para antagonizar las acciones de la sustancia P, la Neuroquinina A y la Neuroquinina B bloqueando los receptores NK1, NK2 y NK3, los compuestos de conformidad con la presente invencion son utiles como medicamentos, en particular para el tratamiento profilactico y terapeutico de condiciones mediadas por taquiquininas, tales como, por ejemplo, los trastornos del CNS, particularmente en desordenes esquizoafectivos, depresion, trastornos de ansiedad, trastornos relacionados con el estres, trastornos del sueno, trastornos cognitivos, trastornos de la personalidad, trastornos de la alimentacion, trastornos neurodegenerativos, trastornos de adiccion, trastornos del animo, disfuncion sexual, dolor y otras condiciones relacionadas con el CNS; inflamacion, trastornos alergicos; emesis; trastornos gastrointestinales, particularmente el sindrome de intestino irritable (lBS); trastornos de la piel; trastornos vasoespasticos, trastornos fibrosantes y del colageno; trastornos relacionados con el mejoramiento o la supresion inmune y los trastornos reumaticos y del control del peso corporal.

公开(公告)号：NO20053598D0

公开(公告)日：2005-07-22

申请号：NO20053598

申请日：2005-07-22

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： JANSSENS FRANS EDUARD ,  LEENAERTS JOSEPH ELISABETH ,  SOMMEN FRANCOIS MARIA ,  BOECK BENOIT CHRISTIAN ALBERT

IPC: A61P25/00 ,  A61P29/00 ,  C07D211/58 ,  C07D211/96 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D513/04 ,  A61K

Abstract: This invention concerns substituted 1-piperidin-3-yl-4-piperidin-4-yl-piperazine derivatives having neurokinin antagonistic activity, in particular NK1 antagonistic activity, a combined NK1/NK3 antagonistic activity and a combined NK1/NK2/NK3 antagonistic activity, their preparation, compositions comprising them and their use as a medicine, in particular for the treatment of schizophrenia, emesis, anxiety and depression, irritable bowel syndrom (IBS), circadian rhythm disturbances, visceral pain, neurogenic inflammation, asthma, micturition disorders such as urinary incontinence and nociception. 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. In view of their capability to antagonize the actions of tachykinins by blocking the neurokinin receptors, and in particular antagonizing the actions of substance P, Neurokinin A and Neurokinin B by blocking the NK1, NK2 and NK3 receptors, the compounds according to the invention are useful as a medicine, in particular in the prophylactic and therapeutic treatment of tachykinin-mediated conditions, such as, for instance CNS disorders, in particular schizoaffective disorders, depression, anxiety disorders, stress-related disorders, sleep disorders, cognitive disorders, personality disorders, eating disorders, neurodegenerative diseases, addiction disorders, mood disorders, sexual dysfunction, pain and other CNS-related conditions; inflammation; allergic disorders; emesis; gastrointestinal disorders, in particular irritable bowel syndrome (IBS); skin disorders; vasospastic diseases; fibrosing and collagen diseases; disorders related to immune enhancement or suppression and rheumatic diseases and body weight control.

公开(公告)号：DE69925036D1

公开(公告)日：2005-06-02

申请号：DE69925036

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：NO318891B1

公开(公告)日：2005-05-18

申请号：NO20012710

申请日：2001-06-01

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：NO20052192A

公开(公告)日：2005-05-04

申请号：NO20052192

申请日：2005-05-04

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： DIELS GASTON STANISLAS MARCELL ,  ROOSBROECK YVES EMIEL MARIA VA ,  JANSSENS FRANS EDUARD ,  LEENAERTS JOSEPH ELISABETH ,  SOMMEN FRANCOIS MARIA ,  BOECK BENOIT CHRISTIAN ALBERT

IPC: C07D20060101 ,  C07D211/58 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04

公开(公告)号：PL369864A1

公开(公告)日：2005-05-02

申请号：PL36986402

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 ,  MARTINEZ-JIMENEZ PEDRO ,  BARTOLOME-NEBREDA JOSE MANUEL ,  GOMEZ-SANCHEZ ANTONIO ,  FERNANDEZ-GADEA FRANCISCO JAVI ,  VAN REEMPTS JOZEF LEO HENRI

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

Abstract: The invention concerns the use of an H1- and/or H2-histamine receptor antagonist for the reduction of intracranial pressure (ICP), in particular for the prevention and treatment of elevated intracranial pressure and/or secondary ischaemia, in particular caused by brain injury, more in particular caused by traumatic (TBI) and non-traumatic brain injury. In particular, the histamine antagonist is selected from the group of acrivastine, alimemazine, antazoline, astemizole, azatadine, azelastine, brompheniramine, buclizine, carbinoxamine, carebastine, cetirizine, chlorcyclizine, chlorpheniramine, cinnarizine, clemastine, clemizole, clocinizine, clonidine, cyclizine, cyproheptadine, descarboethoxyloratidine, dexchlorpheniramine, dimenhydrinate, dimethindene, dimethothiazine, diphenhydramine, diphenylpyraline, doxylamine, ebastine, efletirizine, epinastine, fexofenadine, hydroxyzine, ketotifen, levocabastine, loratidine, meclizine, mequitazine, methdilazine, mianserin, mizolastine, niaprazine, noberastine, norastemizole, oxatomide, oxomemazine, phenbenzamine, pheniramine, picumast, promethazine, pyrilamine, temelastine, terfenadine, trimeprazine, tripelennamine, triprolidine, ranitidine, cimetidine, famotidine, nizatidine, tiotidine, zolantidine, ritanserine, and derivatives thereof and mixtures of any two or more of the foregoing.

公开(公告)号：AU2004246817A1

公开(公告)日：2004-12-23

申请号：AU2004246817

申请日：2004-06-07

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： MEERT THEO FRANS ,  JANSSENS FRANS EDUARD ,  SOMMEN FRANCOIS MARIA ,  LEENAERTS JOSEPH ELISABETH ,  BOECK BENOIT CHRISTIAN ALBERT ,  ROOSBROECK YVES EMIEL MARIA VA

IPC: A61K31/33 ,  A61K31/433 ,  A61K31/4468 ,  A61K31/485 ,  A61K31/496 ,  A61K31/551 ,  A61K45/06 ,  A61P1/08 ,  A61P11/00 ,  A61P25/00 ,  A61P25/02 ,  A61P25/04 ,  A61P25/36

Abstract: This invention concerns novel formulations for opioid-based treatments of pain and/or nociception comprising opioid analgesics and 1,4-di-piperidin-4-yl-piperazine derivatives having neurokinin antagonistic activity, in particular NK 1 antagonistic activity, the use of said formulation for the manufacture of a medicament for the prevention and/or treatment of emesis, pain and/or nociception, in particular in opioid-based acute and chronic pain treatments, more in particular in inflammatory, post-operative, emergency room (ER), breakthrough, neuropathic and cancer pain treatments and the use of an NK 1 -receptor antagonist for the manufacture of a medicament for the prevention and/or treatment of respiratory depression in opioid-based treatments of pain. The pharmaceutical formulations according to the invention comprise a pharmaceutically acceptable carrier and, as active ingredients, a therapeutically effective amount of an opioid analgesic and NK 1 -antagonists according to the general Formula (I) 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. The pharmaceutical composition according to the invention reduces to a large extent a number of unwanted side-effects associated with opioid analgesics, in particular emesis, respiratory depression and tolerance, thereby increasing the total tolerability of said opioids in pain treatment.