公开(公告)号：SK284468B6

公开(公告)日：2005-04-01

申请号：SK13872000

申请日：1999-03-24

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： FREYNE EDDY JEAN EDGARD ,  DIELS GASTON STANISLAS MARCELL ,  MATESANZ-BALLESTEROS MARIA ENC ,  DIAZ-MARTINEZ ADOLFO

IPC: A61K31/44 ,  A61K31/4427 ,  A61K31/443 ,  A61K31/4439 ,  A61P11/06 ,  A61P17/00 ,  A61P29/00 ,  A61P37/08 ,  A61P43/00 ,  C07D401/06 ,  C07D405/14 ,  C07D407/14

Abstract: Described are the compounds of general formula (I), wherein L is hydrogen, -A-B- is bivalent radical -CR4-CR5-, D is O or NR6, R1 is hydrogen, R2 is hydrogen or C1-6alkyl or OH, R3 is hydrogen or C1-6alkyl, R4 and R5 are hydrogen, R6 is CN and Q is substituted pyridyl, a method for the preparation thereof and their use for the manufacture of a medicament for the treatment of atopic and asthmatic diseases, further a composition comprising thereof and method for its preparation.

公开(公告)号：AU760771B2

公开(公告)日：2003-05-22

申请号：AU3147499

申请日：1999-03-24

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： FREYNE EDDY JEAN EDGARD ,  DIELS GASTON STANISLAS MARCELL ,  MATESANZ-BALLESTEROS MARIA ENC ,  DIAZ-MARTINEZ ADOLFO

IPC: A61K31/44 ,  A61K31/4427 ,  A61K31/443 ,  A61K31/4439 ,  A61P11/06 ,  A61P17/00 ,  A61P29/00 ,  A61P37/08 ,  A61P43/00 ,  C07D401/06 ,  C07D405/14 ,  C07D407/14

Abstract: The present invention concerns pyridine derivatives having the formulathe N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein L is hydrogen; C1-6alkyl; C1-6alkyl carbonyl; C1-6alkyloxycarbonyl; substituted C1-6alkyl; C3-6alkenyl; substituted C3-6alkenyl; piperidyl; substituted piperidyl; C1-6alkylsulfonyl or arylsulfonyl; -A-B- is -CR =CR - or-CHR -CHR -; D is O or NR ; R is a hydrogen or C1-4alkyl; R is hydrogen; halo; C1-6alkyl; trifluoromethyl; C3-6cycloalkyl; carboxyl; C1-4alkyl oxycarbonyl; C3-6cycloalkylaminocarbonyl; aryl; Het ; or substituted C1-6alkyl; or R is -O-R or -NH-R ; R is hydrogen, halo, hydroxy, C1-6alkyl or C1-6alkyloxy; or R and R , or R and R taken together may form a bivalent radical; Q is disubstituted pyridine; R and R each independently are hydrogen; C1-6alkyl; difluoromethyl; trifluoromethyl; C3-6cyclo alkyl; a saturated 5-, 6- or 7-membered heterocycle containing one or two heteroatoms selected from oxygen, sulfur or nitrogen; indanyl; 6,7-dihydro-5H-cyclopentapyridyl; bicyclo[2.2.1]-2-heptenyl; bicyclo[2.2.1]heptanyl; C1-6alkylsulfonyl; arylsulfonyl; or substituted C1-10alkyl; having PDE IV and cytokine inhibiting activity. The invention also relates to processes for preparing the compounds of formula (I), pharmaceutical compositions thereof and their use as a medicament.

公开(公告)号：HK1033579A1

公开(公告)日：2001-09-07

申请号：HK01103462

申请日：2001-05-19

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： FREYNE EDDY JEAN EDGARD ,  DIELS GASTON STANISLAS MARCELL ,  MATESANZ-BALLESTEROS MARIA ENC ,  DIAZ-MARTINEZ ADOLFO

IPC: A61K31/44 ,  A61K31/4427 ,  A61K31/443 ,  A61K31/4439 ,  A61P11/06 ,  A61P17/00 ,  A61P29/00 ,  A61P37/08 ,  A61P43/00 ,  C07D401/06 ,  C07D405/14 ,  C07D407/14 ,  C07D ,  A61K

Abstract: The present invention concerns pyridine derivatives having the formulathe N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein L is hydrogen; C1-6alkyl; C1-6alkyl carbonyl; C1-6alkyloxycarbonyl; substituted C1-6alkyl; C3-6alkenyl; substituted C3-6alkenyl; piperidyl; substituted piperidyl; C1-6alkylsulfonyl or arylsulfonyl; -A-B- is -CR =CR - or-CHR -CHR -; D is O or NR ; R is a hydrogen or C1-4alkyl; R is hydrogen; halo; C1-6alkyl; trifluoromethyl; C3-6cycloalkyl; carboxyl; C1-4alkyl oxycarbonyl; C3-6cycloalkylaminocarbonyl; aryl; Het ; or substituted C1-6alkyl; or R is -O-R or -NH-R ; R is hydrogen, halo, hydroxy, C1-6alkyl or C1-6alkyloxy; or R and R , or R and R taken together may form a bivalent radical; Q is disubstituted pyridine; R and R each independently are hydrogen; C1-6alkyl; difluoromethyl; trifluoromethyl; C3-6cyclo alkyl; a saturated 5-, 6- or 7-membered heterocycle containing one or two heteroatoms selected from oxygen, sulfur or nitrogen; indanyl; 6,7-dihydro-5H-cyclopentapyridyl; bicyclo[2.2.1]-2-heptenyl; bicyclo[2.2.1]heptanyl; C1-6alkylsulfonyl; arylsulfonyl; or substituted C1-10alkyl; having PDE IV and cytokine inhibiting activity. The invention also relates to processes for preparing the compounds of formula (I), pharmaceutical compositions thereof and their use as a medicament.

公开(公告)号：NZ503294A

公开(公告)日：2001-08-31

申请号：NZ50329498

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: Compounds of formula (I) may be used in medicaments for the treatment of anxiety, psychosis, schizophrenia, depression, migraine, sleep disorders and addictive properties of drugs of abuse. In formula (I); n is zero, 1, 2, 3, 4, 5 or 6; X is CH2 or O; R1 and R2 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 R1 and R2 taken together with the nitrogen atom to which they are attached may form a morpholinyl ring or radical depicted above, wherein R9, R10, R11 and R12 independently are hydrogen, halo, halomethyl or C1-6alkyl m is 0, 1, 2 or 3; R13, R14, R15 and R16 each independently are hydrogen, C1-6alkyl, aryl or arylcarbonyl; or R15 and R16 taken together may form a bivalent radical C4-5alkanediyl; R17 is hydrogen, C1-6 alkyl, C1-6alkylcarbonyl, halomethylcarbonyl, C1-6alkoxycarbonyl, aryl, di(aryl)methyl or C1-6alkyl substituted with hydroxy, C1-6 alkyloxy, carboxyl, C1-6alkylcarbonyloxy, C1-6alkyloxycarbonyl or aryl; R3 and R4 are both halogen; or R3 is halogen and R4 is hydrogen; or R3 is hydrogen and R4 is halogen; and aryl is phenyl or phenyl substituted with 1, 2 or 3 substituents selected from halo, hydroxy, C1-6alkyl and halomethyl.

公开(公告)号：NO20004906L

公开(公告)日：2000-11-28

申请号：NO20004906

申请日：2000-09-29

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： FREYNE EDDY JEAN EDGARD ,  DIELS GASTON STANISLAS MARCELL ,  MATESANZ-BALLESTEROS MARIA ENC ,  DIAZ-MARTINEZ ADOLFO

IPC: A61K31/44 ,  A61K31/4427 ,  A61K31/443 ,  A61K31/4439 ,  A61P11/06 ,  A61P17/00 ,  A61P29/00 ,  A61P37/08 ,  A61P43/00 ,  C07D401/06 ,  C07D405/14 ,  C07D407/14

Abstract: The present invention concerns pyridine derivatives having the formulathe N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein L is hydrogen; C1-6alkyl; C1-6alkyl carbonyl; C1-6alkyloxycarbonyl; substituted C1-6alkyl; C3-6alkenyl; substituted C3-6alkenyl; piperidyl; substituted piperidyl; C1-6alkylsulfonyl or arylsulfonyl; -A-B- is -CR =CR - or-CHR -CHR -; D is O or NR ; R is a hydrogen or C1-4alkyl; R is hydrogen; halo; C1-6alkyl; trifluoromethyl; C3-6cycloalkyl; carboxyl; C1-4alkyl oxycarbonyl; C3-6cycloalkylaminocarbonyl; aryl; Het ; or substituted C1-6alkyl; or R is -O-R or -NH-R ; R is hydrogen, halo, hydroxy, C1-6alkyl or C1-6alkyloxy; or R and R , or R and R taken together may form a bivalent radical; Q is disubstituted pyridine; R and R each independently are hydrogen; C1-6alkyl; difluoromethyl; trifluoromethyl; C3-6cyclo alkyl; a saturated 5-, 6- or 7-membered heterocycle containing one or two heteroatoms selected from oxygen, sulfur or nitrogen; indanyl; 6,7-dihydro-5H-cyclopentapyridyl; bicyclo[2.2.1]-2-heptenyl; bicyclo[2.2.1]heptanyl; C1-6alkylsulfonyl; arylsulfonyl; or substituted C1-10alkyl; having PDE IV and cytokine inhibiting activity. The invention also relates to processes for preparing the compounds of formula (I), pharmaceutical compositions thereof and their use as a medicament.

公开(公告)号：SK4712000A3

公开(公告)日：2000-10-09

申请号：SK4712000

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：CZ20001136A3

公开(公告)日：2000-08-16

申请号：CZ20001136

申请日：1998-10-06

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： ANDR S-GIL JOS 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：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：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：NO317159B1

公开(公告)日：2004-08-30

申请号：NO20001792

申请日：2000-04-06

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： FERNANDEZ-GADEA FRANCISCO JAVIER ,  ANDRES-GIL JOSE IGNACIO ,  DIAZ-MARTINEZ ADOLFO ,  GIL-LOPETEGUI PILAR

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.