公开(公告)号：CA2587936A1

公开(公告)日：2006-06-15

申请号：CA2587936

申请日：2005-12-06

Applicant: SOLVAY PHARM BV

Inventor： KRUSE CORNELIS G ,  SMID PIETER ,  VAN HES ROELOF ,  TULP MARTINUS TH M

IPC: C07D401/14 ,  A61K31/519 ,  A61P25/00 ,  C07D471/04 ,  C07D487/04 ,  C07D513/04

Abstract: The present invention relates to a group of novel tetrahydropyridin-4-yl indoles with a dual mode of action: serotonin reuptake inhibition and affinity for dopamine -D 2 receptors, to methods for the preparation of these compounds and to novel intermediates useful for the synthesis of said tetrahydropyridin-4-yl indoles. The invention also relates to the use of a compound disclosed herein for the manufacture of a medicament giving a beneficial effect. The invention relates to novel tetrahydropyridin -4-yl indoles of the formula (I) and tautomers, stereoisomers, prodrugs, N -oxides, pharmacologically acceptable salts, hydrates and solvates thereof , wherein: - R 1 is hydrogen, halogen, alkyl (C 1-3 ) or alkoxy(C 1-3 ), CN or CF 3 , - R 2 is hydrogen or alkyl (C 1-3 ), R 3 is hydrogen or alkyl (C 1-3 ), - Z is hydrogen or alkyl (C 1-3 ), alkoxy(C 1-3 ) or alkylthio(C 1-3 ), - A is hydrogen or alkyl (C 1-3 ), or - A and Z together form a saturated or (partly) unsaturated 5 - or 6- membered ring which may be substituted with halogen, alkyl (C 1-3 ) or phenyl, in which ring Z represents carbon, sulfur of nitrogen .

公开(公告)号：ES2230521T3

公开(公告)日：2005-05-01

申请号：ES02784838

申请日：2002-07-03

Applicant: SOLVAY PHARM BV

Inventor： VAN MAARSEVEEN JAN H ,  VAN SCHARRENBURG GUSTAAF J M ,  TULP MARTINUS TH M ,  MCCREARY ANDREW C ,  IWEMA BAKKER WOUTER I ,  COOLEN HEIN K A C

IPC: A61K31/495 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/541 ,  A61P1/00 ,  A61P1/04 ,  A61P1/08 ,  A61P3/04 ,  A61P9/10 ,  A61P9/12 ,  A61P11/00 ,  A61P11/02 ,  A61P11/06 ,  A61P11/08 ,  A61P13/02 ,  A61P13/10 ,  A61P17/00 ,  A61P17/02 ,  A61P17/04 ,  A61P17/06 ,  A61P19/02 ,  A61P25/00 ,  A61P25/02 ,  A61P25/04 ,  A61P25/06 ,  A61P25/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/20 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/30 ,  A61P29/00 ,  A61P35/00 ,  A61P37/08 ,  A61P43/00 ,  C07D241/04 ,  C07D401/14 ,  C07D403/06 ,  C07D403/14 ,  C07D405/06 ,  C07D405/14 ,  C07D409/06 ,  C07D413/14 ,  C07D471/04

Abstract: Compuestos de la fórmula general (1) **(Fórmula)** en la que: X representa fenilo o piridilo sustituido con 1 ó 2 sustituyentes del grupo CH3, CF3, OCH3, halógeno, ciano y 520 CF3-tetrazol-1-ilo Y representa 2- ó 3-indolilo, fenilo, 7-aza-indol-3-ilo o 3-indazolilo, 2-naftilo, 3-benzo[b]tiofenilo o 2-benzofuranilo, grupos que pueden estar sustituidos con uno o más halógenos o alquilos (125 3C) n tiene el valor 0-3 m tiene el valor 0-2 R1 representa NH2, NH-alquilo (1-3C), dialquilo (1-3C)N, morfolino o morfolino sustituido con uno o dos grupos metilo y/o metoximetilo, tiomorfolino, 1, 1-dioxotiomorfolino, 2-, 3- ó 4-piridilo o 4-CH3-piperazinilo R2 es hidrógeno, alquilo (1-4C) o fenilo, o R2 junto con (CH2)m en el que m es 1, y los átomos intermedios de carbono, nitrógeno y oxígeno forma un grupo isoxazolilo o 4, 5-dihidroisoxazolilo, R3 y R4 representan independientemente hidrógeno o metilo, o R3 y R4 juntos son oxígeno, y sus sales fisiológicamente aceptables.

公开(公告)号：DK1406894T3

公开(公告)日：2005-03-14

申请号：DK02784838

申请日：2002-07-03

Applicant: SOLVAY PHARM BV

Inventor： TULP MARTINUS TH M ,  IWEMA BAKKER WOUTER I ,  COOLEN HEIN K A C ,  HERREMANS ARNOLDUS H J ,  VAN DEN HOOGENBAND ADRIANUS ,  VAN MAARSEVEEN JAN H ,  VAN SCHARRENBURG GUSTAAF J M ,  MCCREARY ANDREW C

IPC: A61K31/495 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/541 ,  A61P1/00 ,  A61P1/04 ,  A61P1/08 ,  A61P3/04 ,  A61P9/10 ,  A61P9/12 ,  A61P11/00 ,  A61P11/02 ,  A61P11/06 ,  A61P11/08 ,  A61P13/02 ,  A61P13/10 ,  A61P17/00 ,  A61P17/02 ,  A61P17/04 ,  A61P17/06 ,  A61P19/02 ,  A61P25/00 ,  A61P25/02 ,  A61P25/04 ,  A61P25/06 ,  A61P25/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/20 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/30 ,  A61P29/00 ,  A61P35/00 ,  A61P37/08 ,  A61P43/00 ,  C07D241/04 ,  C07D401/14 ,  C07D403/06 ,  C07D403/14 ,  C07D405/06 ,  C07D405/14 ,  C07D409/06 ,  C07D413/14 ,  C07D471/04

Abstract: The present invention relates to a group of novel piperazine oxime derivatives having interesting NK-1 antagonistic activity. The invention relates to compounds of the general formula (1) wherein: X represents phenyl or pyridyl substituted with 1 or 2 substituents from the group CH 3 , CF 3 , OCH 3 , halogen, cyano and 5-CF 3 -tetrazol-1-yl; Y represents 2- or 3-indolyl, phenyl, 7-aza-indol-3-yl or 3-indazolyl, 2-naphthyl, 3-benzo[b]thiophenyl, 2-benzofuranyl, which groups may be substituted with one or more halogen or alkyl (1-3C); n has the value 0-3; m has the value 0-2; R 1 represents NH 2 , NH-alkyl (1-3C), dialkyl (1-3C)N, morpholino or morpholino substituted with one or two methyl and/or methoxymethyl groups, thiomorpholino, 1,1-dioxothiomorpholino, 2-, 3- or 4-pyridyl or 4-CH 3 -piperazinyl; R 2 is hydrogen, alkyl (1-4C) or phenyl, or R 2 together with (CH 2 ) m wherein m is 1, and the intermediate carbon, nitrogen and oxygen atoms forms an isoxazolyl or a 4,5-dihydroisoxazolyl group; R 3 and R 4 independently represent hydrogen or methyl, or R 3 and R 4 together are oxygen. The invention also relates to a method for the preparation of the novel compounds, and to pharmaceutical compositions comprising compounds with formula (1) as an active ingredient and the use of these compounds for the treatment of disorders in which neurokinin-1 receptors are involved

公开(公告)号：PL366841A1

公开(公告)日：2005-02-07

申请号：PL36684102

申请日：2002-07-03

Applicant: SOLVAY PHARM BV

Inventor： VAN MAARSEVEEN JAN H ,  VAN SCHARRENBURG GUSTAAF J M ,  TULP MARTINUS TH M ,  MCCREARY ANDREW C ,  IWEMA BAKKER WOUTER I ,  COOLEN HEIN K A C ,  HERREMANS ARNOLDUS H J ,  VAN DEN HOOGENBAND ADRIANUS

IPC: A61K31/495 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/541 ,  A61P1/00 ,  A61P1/04 ,  A61P1/08 ,  A61P3/04 ,  A61P9/10 ,  A61P9/12 ,  A61P11/00 ,  A61P11/02 ,  A61P11/06 ,  A61P11/08 ,  A61P13/02 ,  A61P13/10 ,  A61P17/00 ,  A61P17/02 ,  A61P17/04 ,  A61P17/06 ,  A61P19/02 ,  A61P25/00 ,  A61P25/02 ,  A61P25/04 ,  A61P25/06 ,  A61P25/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/20 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/30 ,  A61P29/00 ,  A61P35/00 ,  A61P37/08 ,  A61P43/00 ,  C07D241/04 ,  C07D401/14 ,  C07D403/06 ,  C07D403/14 ,  C07D405/06 ,  C07D405/14 ,  C07D409/06 ,  C07D413/14 ,  C07D471/04

Abstract: The present invention relates to a group of novel piperazine oxime derivatives having interesting NK-1 antagonistic activity. The invention relates to compounds of the general formula (1) wherein: X represents phenyl or pyridyl substituted with 1 or 2 substituents from the group CH 3 , CF 3 , OCH 3 , halogen, cyano and 5-CF 3 -tetrazol-1-yl; Y represents 2- or 3-indolyl, phenyl, 7-aza-indol-3-yl or 3-indazolyl, 2-naphthyl, 3-benzo[b]thiophenyl, 2-benzofuranyl, which groups may be substituted with one or more halogen or alkyl (1-3C); n has the value 0-3; m has the value 0-2; R 1 represents NH 2 , NH-alkyl (1-3C), dialkyl (1-3C)N, morpholino or morpholino substituted with one or two methyl and/or methoxymethyl groups, thiomorpholino, 1,1-dioxothiomorpholino, 2-, 3- or 4-pyridyl or 4-CH 3 -piperazinyl; R 2 is hydrogen, alkyl (1-4C) or phenyl, or R 2 together with (CH 2 ) m wherein m is 1, and the intermediate carbon, nitrogen and oxygen atoms forms an isoxazolyl or a 4,5-dihydroisoxazolyl group; R 3 and R 4 independently represent hydrogen or methyl, or R 3 and R 4 together are oxygen. The invention also relates to a method for the preparation of the novel compounds, and to pharmaceutical compositions comprising compounds with formula (1) as an active ingredient and the use of these compounds for the treatment of disorders in which neurokinin-1 receptors are involved

公开(公告)号：BR0210080A

公开(公告)日：2004-06-22

申请号：BR0210080

申请日：2002-07-03

Applicant: SOLVAY PHARM BV

Inventor： MAARSEVEEN JAN H VAN ,  SCHARRENBURG GUSTAAF J M VAN ,  TULP MARTINUS TH M ,  MCCREARY ANDREW C ,  BAKKER WOUTER I IWEMA ,  COOLEN HEIN K A ,  HERREMANS ARNOLDUS H J ,  HOOGENBAND ADRIANUS VAN DEN

IPC: A61K31/495 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/541 ,  A61P1/00 ,  A61P1/04 ,  A61P1/08 ,  A61P3/04 ,  A61P9/10 ,  A61P9/12 ,  A61P11/00 ,  A61P11/02 ,  A61P11/06 ,  A61P11/08 ,  A61P13/02 ,  A61P13/10 ,  A61P17/00 ,  A61P17/02 ,  A61P17/04 ,  A61P17/06 ,  A61P19/02 ,  A61P25/00 ,  A61P25/02 ,  A61P25/04 ,  A61P25/06 ,  A61P25/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/20 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/30 ,  A61P29/00 ,  A61P35/00 ,  A61P37/08 ,  A61P43/00 ,  C07D241/04 ,  C07D401/14 ,  C07D403/06 ,  C07D403/14 ,  C07D405/06 ,  C07D405/14 ,  C07D409/06 ,  C07D413/14 ,  C07D471/04

Abstract: The present invention relates to a group of novel piperazine oxime derivatives having interesting NK-1 antagonistic activity. The invention relates to compounds of the general formula (1) wherein: X represents phenyl or pyridyl substituted with 1 or 2 substituents from the group CH 3 , CF 3 , OCH 3 , halogen, cyano and 5-CF 3 -tetrazol-1-yl; Y represents 2- or 3-indolyl, phenyl, 7-aza-indol-3-yl or 3-indazolyl, 2-naphthyl, 3-benzo[b]thiophenyl, 2-benzofuranyl, which groups may be substituted with one or more halogen or alkyl (1-3C); n has the value 0-3; m has the value 0-2; R 1 represents NH 2 , NH-alkyl (1-3C), dialkyl (1-3C)N, morpholino or morpholino substituted with one or two methyl and/or methoxymethyl groups, thiomorpholino, 1,1-dioxothiomorpholino, 2-, 3- or 4-pyridyl or 4-CH 3 -piperazinyl; R 2 is hydrogen, alkyl (1-4C) or phenyl, or R 2 together with (CH 2 ) m wherein m is 1, and the intermediate carbon, nitrogen and oxygen atoms forms an isoxazolyl or a 4,5-dihydroisoxazolyl group; R 3 and R 4 independently represent hydrogen or methyl, or R 3 and R 4 together are oxygen. The invention also relates to a method for the preparation of the novel compounds, and to pharmaceutical compositions comprising compounds with formula (1) as an active ingredient and the use of these compounds for the treatment of disorders in which neurokinin-1 receptors are involved