公开(公告)号：DE60216627T2

公开(公告)日：2007-09-20

申请号：DE60216627

申请日：2002-10-10

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： JANSSENS F E ,  LEENAERTS J E ,  FERNANDEZ-GADEA FRANCISCO JAVI ,  GOMEZ-SANCHEZ ANTONIO ,  MEERT THEO

IPC: C07D401/04 ,  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 ,  C07D401/14 ,  C07D413/14 ,  C07D417/14

Abstract: The present invention relates to novel 4-phenyl-4-[ 1 H-imidazol-2-yl]-piperidine derivatives according to Formula (I) the pharmaceutically acceptable acid or base addition salts thereof, the stereochemically isomeric forms thereof, the tautomeric forms thereof and the N-oxide forms thereof. In particular are claimed compounds according to Formula (I) in which A=B is C-O or SO 2 , X is a covalent bond, R 1 is alkyloxy, alkyloxyalkyl, Ar or NR 9 R 10 , wherein R 9 and R 10 each independently are hydrogen or Ar; or A=B and R 1 together form a benzoxazolyl radical; p is zero, R 3 is benzyl optionally substituted with hydroxy, alkyl or alkyloxycarbonyl and R 4 and R 5 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 particular as selective non-peptide delta-opioid agonists for use in the treatment of various pain conditions.

公开(公告)号：PL194673B1

公开(公告)日：2007-06-29

申请号：PL33257397

申请日：1997-09-24

Applicant: JANSSEN PHARMACEUTICA NV

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

IPC: C07D233/44 ,  A61K31/00 ,  A61K31/415 ,  A61K31/4164 ,  A61K31/4168 ,  A61K31/4178 ,  A61P11/00 ,  A61P11/06 ,  A61P17/00 ,  A61P29/00 ,  A61P37/00 ,  A61P37/08 ,  C07D233/48 ,  C07D233/88 ,  C07D405/12

Abstract: PCT No. PCT/EP97/05322 Sec. 371 Date Mar. 19, 1999 Sec. 102(e) Date Mar. 19, 1999 PCT Filed Sep. 24, 1997 PCT Pub. No. WO98/14432 PCT Pub. Date Apr. 9, 1998The present invention concerns 2-cyanoiminoimidazole derivatives having the formula the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein R1 and R2 each independently are hydrogen; C1-6alkyl; difluoromethyl; trifluoromethyl; C3-6cycloalkyl; a saturated 5-, 6- or 7-membered heterocycle containing one or two heteroatoms selected from oxygen, sulfur or nitrogen; indanyl; 6,7-dihydro-5H-cyclopentapyridinyl; bicyclo[2.2.1]-2-heptenyl; bicyclo[2.2.1]heptanyl; C1-6alkylsulfonyl; arylsulfonyl; or substituted C1-10alkyl; R3 is hydrogen, halo or C1-6alkyloxy; R4 is hydrogen; halo; C1-6alkyl; trifluoromethyl; C3-6cycloalkyl; carboxyl; C1-4alkyloxycarbonyl; C3-6cycloalkylaminocarbonyl; aryl; Het1; or substituted C1-6alkyl; or R4 is -O-R7 or -NH-R8; R5 is hydrogen, halo, hydroxy, C1-6alkyl or C1-6alkyloxy; R6 is a hydrogen or C1-4alkyl; or R4 and R6, or R4 and R5 taken together may form a bivalent radical; -A-B- is -CR10=CR11- or -CHR10-CHR11-; L is hydrogen; C1-6alkyl; C1-6alkylcarbonyl; C1-6alkyloxycarbonyl; substituted C1-6alkyl; C3-6alkenyl; substituted C3-6alkenyl; piperidinyl; substituted piperidinyl; C1-6alkylsulfonyl or arylsulfonyl; having PDE IV and cytokine inhibiting activity. The invention also relates to processes for preparing the compounds of formula (I) and pharmaceutical compositions thereof.

公开(公告)号：CA2211889C

公开(公告)日：2006-10-10

申请号：CA2211889

申请日：1996-01-30

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： MATESANZ-BALLESTEROS MARIA ENC ,  FERNANDEZ-GADEA FRANCISCO JAVI ,  ANDRES-GIL JOSE IGNACIO ,  VAN LOMMEN GUY ROSALIA EUGENE

IPC: C07D491/056 ,  A61K31/435 ,  A61K31/495 ,  A61K31/53 ,  A61P9/08 ,  A61P25/04 ,  A61P25/06 ,  C07D491/04

Abstract: The present invention is concerned with compounds of formula (I), the N-oxide forms, the pharmaceutically acceptable acid addition salts and the stereochemically isomeric forms thereof, wherein =a1-a2=a3-a4= is a bivalent radical of formula (a): =N-CH=CH-CH=, (b): =CH-NCH-CH=, (c): =CH-CH=N-CH=, (d): =CH-CH=CH-N=, wherein one or two hydrogen atoms can be substituted by halo hydroxy, C1-6 alkyl or C1-6 alkyloxy; R1 is hydrogen or C1-6 alkyl; R2 is hydrogen or C1-6 alkyl; R3 is hydrogen or C1-6 alkyl; Alk1 is C1-5 alkanediyl; Alk2 is C2-15 alkanediyl; Q is a five- or six-membered heterocyclic ring containing at lea st one nitrogen atom or a radical of formula -C(NR5R6)=C-R4 wherein R4 is hydrogen, cyano aminocarbonyl or C1-6 alkyl; R5 is hydrogen C1 -6 alkyl, C3-6 alkenyl or C3-6 alkynyl; R6 is hydrogen or C1-6 alkyl; or R5 and R6 taken together may form a bivalent radical of formula - (CH2)4- or -(CH2)5-. Pharmaceutical compositions, preparations and use as a medicine are described.

公开(公告)号：CZ296928B6

公开(公告)日：2006-07-12

申请号：CZ20001136

申请日：1998-10-06

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： ANDRUS-GIL JOSU IGNACIO ,  FERNANDEZ-GADEA FRANCISCO JAVI ,  GIL-LOPETEGUI PILAR ,  DIAZ-MARTINEZ ADOLFO

IPC: C07D493/04 ,  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 ,  C07D307/93 ,  C07D401/06 ,  C07D405/06

Abstract: Tetracyklické deriváty tetrahydrofuranu substituované halogenem vzorce I, jejich N-oxidy, farmaceuticky prijatelné soli a stereochemicky izomerní formy, kde n znamená císlo nula, 1, 2, 3, 4, 5 nebo 6; X je CH.sub.2.n. nebo kyslík; R.sup.1.n. a R.sup.2.n. jsou kazdý nezávisle vodík, C.sub.1-6.n.alkyl, C.sub.1-6.n.alkylkarbonyl, halogenmethylkarbonyl nebo C.sub.1-6.n.alkyl substituovaný hydroxylem,C.sub.1-6.n.alkyloxy, karboxylem, C.sub.1-6.n.alkylkarbonyloxy, C.sub.1-6.n.alkyloxykarbonylem neboarylem; nebo R.sup.1.n. a R.sup.2.n. spolecne s atomem dusíku, ke kterému jsou pripojeny, mohou tvorit morfolinyl nebo poprípade substituovaný heterocyklus; R.sup.3.n. a R.sup.4.n. jsou oba halogen; nebo R.sup.3.n. je halogen a R.sup.4.n. je vodík; nebo R.sup.3.n. je vodík a R.sup.4.n. je halogen; a aryl je fenyl nebo fenyl substituovaný 1, 2 nebo3 substituenty vybranými ze skupiny, kterou tvoríhalogen, hydroxyl, C.sub.1-6.n.alkyl a halogenmethyl. Deriváty vzorce I se hodí pro lécení úzkosti,psychózy, schizofrenie, deprese, poruch spánku a návykových vlastností zneuzívaných léciv.

公开(公告)号：ES2250988T3

公开(公告)日：2006-04-16

申请号：ES96911969

申请日：1996-03-28

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： FREYNE EDDY JEAN EDGARD ,  DIELS GASTON STANISLAS MARCELL ,  ANDRES-GIL JOSE IGNACIO ,  FERNANDEZ-GADEA FRANCISCO JAVI

IPC: A61K31/415 ,  A61K31/4166 ,  A61P11/00 ,  A61P17/00 ,  A61P29/00 ,  A61P37/08 ,  C07D233/32 ,  C07D233/38 ,  C07D233/70 ,  C07D405/04 ,  C07D405/06

Abstract: LA PRESENTE INVENCION SE REFIERE A LOS COMPUESTOS DE FORMULA (I), A LAS FORMAS N DO O BASE FARMACEUTICAMENTE ACEPTABLES Y A LAS FORMAS ESTEREOQUIMICAMENTE ISOMERICAS DE LOS MISMOS, EN LOS QUE R SUP,1} Y R SUP,2} CADA UNO INDEPENDIENTEMENTE SON HIDROGENO; ALQUILO C SUB,1} C SUB,3} EMBROS QUE CONTIENE UNO O DOS HETEROATOMOS SELECCIONADOS DE ENTRE OXIGENO, AZUFRE O NITROGENO; INDANILO; BICICLO[2.2.1] USTITUIDO; R SUP,3} ES HIDROGENO, HALO O ALQUILOXI C SUB,1} C SUB,6}; =C=X ES UN RADICAL BIVALENTE DE FORMULA =C=O; =C=CH ODIILO C SUB,1} ORMULA: -CR SUP,6}=CR SUP,7} -; L ES HIDROGENO; ALQUILO C SUB,1} 1} LO OPCIONALMENTE SUSTITUIDO; PIPERIDINILO OPCIONALMENTE SUSTITUIDO; ALQUILSULFONILO O ARILSULFONILO C SUB,1} LO ES FENILO OPCIONALMENTE SUSTITUIDO; HET SUP,1} ES MORFOLINILO O PIRIDINILO OPCIONALMENTE SUSTITUIDO, O, O; Y HET SUB,2} ES MORFOLINILO O PIPERIDINILO OPCIONALMENTE SUSTITUIDO, QUE POSEEN ACTIVIDAD INHIBIDORA DE PDE IV Y CITOQUINA. LA INVENCION SE REFIERE TAMBIEN A PROCESOS PARA LA PREPARACION DE LOS COMPUESTOS DE FORMULA (I) Y COMPOSICIONES FARMACEUTICAS DE LOS MISMOS.

公开(公告)号：OA11898A

公开(公告)日：2006-04-10

申请号：OA00000105

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: 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 ,  C07D307/93 ,  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.

公开(公告)号：EA006507B1

公开(公告)日：2005-12-29

申请号：EA200400545

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: Настоящееизобретениеотноситсяк новым 4-фенил-4-[1H-имидазол-2-ил]пиперидиновымпроизводнымформулы (I)ихфармацевтическиприемлемымсолямприсоединениякислотилиоснований, ихстереохимическиизомернымформам, ихтаутомернымформами их N-оксидам. Вчастности, заявленысоединенияформулы (I), где A=B представляетсобой C=O или SO, X представляетсобойковалентнуюсвязь, Rпредставляетсобойалкилокси, алкилоксиалкил, Ar или NRR, где Rи R, каждыйнезависимо, представляютсобойводородили Ar; или A=B и Rвместеобразуютрадикалбензоксазолил; p равеннулю, Rпредставляетсобойбензил, необязательнозамещенныйгидрокси, алкиломилиалкилоксикарбонилом, икаждыйиз Rи Rпредставляетсобойводород. Изобретениетакжеотноситсяк способамполучениясоединенийпоизобретениюи ихприменениюв медицине, вчастности, вкачествеселективныхнепептидныхагонистов d-опиоидов, дляпримененияприлеченииразличныхболей.

公开(公告)号：EA005760B1

公开(公告)日：2005-06-30

申请号：EA200300049

申请日：2001-06-13

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： VAN EMELEN KRISTOF ,  DE BRUYN MARCEL FRANS LEOPOLD ,  ALCAZAR-VACA MANUEL JESIS ,  ANDRES-GIL JOSE IGNACIO ,  FERNANDEZ-GADEA FRANCISCO JAVI ,  MATESANZ-BALLESTEROS MARIA ENC ,  BARTOLOME-NEBREDA JOSE MANUEL

IPC: C07D491/056 ,  A61K31/435 ,  A61K31/436 ,  A61K31/4545 ,  A61K31/513 ,  A61K31/5383 ,  A61P1/00 ,  A61P1/14 ,  C07D411/04 ,  C07D491/04 ,  C07D491/052 ,  C07D491/06 ,  C07D497/04 ,  C07D498/04

Abstract: Настоящееизобретениекасаетсясоединенийформулы (I), ихстереохимическиизомерныхформ, N-оксидныхформ, фармацевтическиприемлемыхаддитивныхсолейкислот, где -a=a-a=a- представляетбивалентныйрадикалформулы -N=CH-CH=CH- (a-1), -CH=N-CH=CH- (a-2), -CH=CH-N=CH- (a-3), -CH=CH-CH=N- (a-4), -N=CH-N=CH- (a-6), -Z-Z- представляетбивалентныйрадикалформулы -Y-CH(R)-CH- (b-1), Y-CH(R)-O- (b-2), -Y-CH(R)-CH-O- (b-3), -Y-CH(R)-CH-S- (b-4), -Y-CH(R)-CH-NH (b-5) или -Y-CH(R)-CH-CH- (b-6), где, есливозможно, необязательноодинилидваатомаводороданаодномилиразныхатомахуглеродаилиазотамогутбытьзамещены Cалкилом; Yпредставляеткислородилисеру; Alkпредставляет Cалкандиил; R, Rи R, каждыйнезависимо, выбранизводорода, Cалкилаилигалогена; Rпредставляетводород; -A- представляетбивалентныйрадикалформулы (c-1) или (c-2), где m равно 0 или 1; Alkпредставляет Cалкил, необязательнозамещенныйоднимилиболеегидрокси; Rпредставляетводород, гидрокси, гидрокси-Cалкил, Cалкилокси, Cалкилоксикарбонилилигидроксикарбонил; Rпредставляетрадикалформулы (d-1), где X представляеткислород; Rпредставляетводород, Cалкил, Cциклоалкил, фенилилифенилметил; и Q представляетбивалентныйрадикалформулы -CH-CH- (e-1), -CH-CH-CH- (e-2), -CH-CO- (e-5), -(CH)-CO- (e-7), гденеобязательноодинилидваатомаводороданаодномилиразныхатомахуглеродамогутбытьзаменены Cалкилом, гидроксиилифенилом. Раскрытыспособыполученияуказанныхпродуктов, фармацевтическиекомпозиции, содержащиеуказанныепродукты, иихприменениев качествелекарственныхсредств, вчастности, длялечениясостояний, которыеотносятсяк нарушеннойфундальнойаккомодации.

公开(公告)号：NZ531679A

公开(公告)日：2005-02-25

申请号：NZ53167902

申请日：2002-10-10

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： JANSSENS FRANS EDUARD ,  LEENAERTS JOSEH 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: A compound according to Formula (I); a pharmaceutical composition comprising the compound; and the use of the compound or pharmaceutical composition for the manufacture of a medicament for use in the treatment of pain e.g. centrally mediated pain, peripherally mediated pain, structural or soft tissue injury related pain, progressive disease related pain, neuropathic pain, acute or chronic pain wherein the chronic pain may be caused by neuropathic conditions, diabetic peripheral neuropathy, post-herpetic neuralgia, trigeminal neuralgia, post-stroke pain syndromes, cluster or migraine headaches, arthritis, psoriasis, asthma, inflammatory bowel disease, respiratory function disorder, functional diarrhea, non-ulcerogenic dyspepsia, incontinence or irritable bowel syndrome.

公开(公告)号：PL363264A1

公开(公告)日：2004-11-15

申请号：PL36326402

申请日：2002-02-13

Applicant: JANSSEN PHARMACEUTICA NV

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

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