公开(公告)号：DE69912590T2

公开(公告)日：2004-09-16

申请号：DE69912590

申请日：1999-03-24

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： FREYNE JEAN ,  DIELS STANISLAS ,  MATESANZ-BALLESTEROS CAMPO DE ,  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：EA004207B1

公开(公告)日：2004-02-26

申请号：EA200001009

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 ,  C07D401/14

Abstract: Настоящееизобретениекасаетсяпроизводныхпиридина, имеющихформулу (I), их N-оксидныхформ, фармацевтическиприемлемыхаддитивныхсолейи стереохимическиизомерныхформ, где L обозначаетводород; -А-В- обозначает -CR=CR- или -CHR-CHR-; D обозначаетО или NR; Rобозначаетводород; Rобозначаетводород; Cалкилилигидрокси; Rобозначаетводородили Cалкил; Rи R, каждыйнезависимо, выбраныизводородаили Cалкила; Rи R, каждыйнезависимо, обозначаютводород; Cалкил; дифторметил; Сциклоалкил; насыщенный 5-членныйгетероцикл, содержащийодинилидвагетероатома, выбранныхизкислорода, серыилиазота; инданил; Cалкил; имеющихингибирующуюактивностьв отношении PDE IV ицитокина. Изобретениетакжеотноситсяк способамполучениясоединенийформулы (I), ихфармацевтическимкомпозициями ихприменениюв качествемедикамента.

公开(公告)号：AP1239A

公开(公告)日：2004-01-15

申请号：AP2000001784

申请日：1998-10-06

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： ANDRES-GIL JOSE IGNACIO ,  FERNANDEZ-GADEA FRANCISCO JAVIER ,  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 A'-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 CHa or O; R1 and R2 each independently are hydrogen, Ci-ealkyl, Ci-«alkylcarbonyl, halomethylcarbonyl or Ci-ealkyl substituted with hydroxy, Ci-ealkyloxy, carboxyl, Ci_«alkylcarbonyloxy, Ci-ealkyloxycarbonyl or aryl; or R1 and R2 taken together with the nitrogen atom to which they are attached may form a morphoiinyl ring or an optionally substituted heterocycle; 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, Ci-6alkyl and halomethyl. The compounds of formula (I) may be used as therapeutic agents.

公开(公告)号：SI1021432T1

公开(公告)日：2003-08-31

申请号：SI9830430

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：PT1021432E

公开(公告)日：2003-08-29

申请号：PT98950107

申请日：1998-10-06

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： FERNANDEZ-GADEA FRANCISCO JAVI ,  ANDRES-GIL JOSE IGNACIO ,  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：DK1021432T3

公开(公告)日：2003-07-14

申请号：DK98950107

申请日：1998-10-06

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： GIL-LOPETEGUI PILAR ,  ANDRES-GIL JOSE IGNACIO ,  FERNANDEZ-GADEA FRANCISCO JAVI ,  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：HU0101239A2

公开(公告)日：2002-05-29

申请号：HU0101239

申请日：1999-03-24

Applicant: JANSSEN PHARMACEUTICA NV

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

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：EE200000569A

公开(公告)日：2002-04-15

申请号：EEP200000569

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 ,  A61K31/435

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：AU737334B2

公开(公告)日：2001-08-16

申请号：AU9629698

申请日：1998-10-06

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： GIL JOSE IGNACIO ANDRES ,  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：TR200000918T2

公开(公告)日：2000-07-21

申请号：TR200000918

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.