公开(公告)号：HRP20040273A2

公开(公告)日：2005-02-28

申请号：HRP20040273

申请日：2004-03-19

Applicant: SOLVAY PHARM BV

Inventor： BOER DIRK DE ,  COOLEN HEIN ,  HESSELINK MAYKE ,  BAKKER WOUTER IWEMA ,  KUIL GIJSBERT ,  MAARSEVEEN JAN VAN ,  MCCREARY ANDREW ,  SCHARRENBURG GUSTAAF J M VAN

IPC: A61K31/4985 ,  A61K31/5377 ,  A61K31/5386 ,  A61K31/541 ,  A61P1/00 ,  A61P1/08 ,  A61P7/10 ,  A61P9/00 ,  A61P9/10 ,  A61P9/12 ,  A61P11/06 ,  A61P11/08 ,  A61P11/16 ,  A61P13/02 ,  A61P13/10 ,  A61P17/00 ,  A61P17/02 ,  A61P17/04 ,  A61P17/06 ,  A61P19/00 ,  A61P19/02 ,  A61P25/00 ,  A61P25/04 ,  A61P25/06 ,  A61P25/18 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P27/16 ,  A61P29/00 ,  A61P37/08 ,  A61P43/00 ,  C07D471/04 ,  C07D487/04 ,  C07D491/10 ,  C07D519/00

Abstract: The present invention relates to a group of unique diazabicyclo alkane derivatives having interesting neurokinin-NK 1 receptor antagonistic activity represented by the general formula (1) wherein: R 1 represents phenyl, 2-indolyl, 3-indolyl, 3-indazolyl or benzo[b]thiophen-3-yl, which groups may be substituted with halogen or alkyl (1-3C), R 2 and R 3 independently represent halogen, H, OCH 3 , CH 3 and CF 3 , R 4 , R 5 and R 6 independently represent H, OH, O-alkyl(1-4C), CH 2 OH, NH 2 , dialkyl(1-3C)N, pyrrolidin-1-yl, piperidin-1-yl, morpholin-4-yl or morpholin-4-yl substituted with one or two methyl or methoxymethyl groups, morpholin-4-ylamino, morpholin-4-ylmethyl, imidazol-1-yl, thiomorpholin-4-yl, 1,1-dioxothiomorpholin-4-yl or 3-oxa-8-azabicyclo[3.2.1]oct-8-yl; R 4 and R 5 together may represent a keto, a 1,3-dioxan-2-yl or a 1,3-dioxolan-2-yl group, X represents either O or S, n has the value of 1, 2 or 3, a is the asymmetrical carbon atom 8a, 9a or 10a when n equals 1, 2 or 3 respectively The invention also relates to a method for the preparation of the novel compounds, and to pharmaceutical compositions containing at least one of these compounds as an active ingredient.

公开(公告)号：AT435863T

公开(公告)日：2009-07-15

申请号：AT03720571

申请日：2003-04-02

Applicant: SOLVAY PHARM BV

Inventor： DE BOER DIRK ,  COOLEN HEIN ,  HESSELINK MAYKE ,  IWEMA BAKKER WOUTER ,  KUIL GIJSBERT ,  VAN MAARSEVEEN JAN ,  MCCREARY ANDREW ,  VAN SCHARRENBURG GUSTAAF

IPC: C07D471/04 ,  A61K31/4985 ,  A61K31/5377 ,  A61K31/5386 ,  A61K31/541 ,  A61P1/00 ,  A61P1/08 ,  A61P7/10 ,  A61P9/00 ,  A61P9/10 ,  A61P9/12 ,  A61P11/06 ,  A61P11/08 ,  A61P11/16 ,  A61P13/02 ,  A61P13/10 ,  A61P17/00 ,  A61P17/02 ,  A61P17/04 ,  A61P17/06 ,  A61P19/00 ,  A61P19/02 ,  A61P25/00 ,  A61P25/04 ,  A61P25/06 ,  A61P25/18 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P27/16 ,  A61P29/00 ,  A61P37/08 ,  A61P43/00 ,  C07D487/04 ,  C07D491/10 ,  C07D519/00

Abstract: The present invention relates to a group of unique diazabicyclo alkane derivatives having interesting neurokinin-NK 1 receptor antagonistic activity represented by the general formula (1) wherein: R 1 represents phenyl, 2-indolyl, 3-indolyl, 3-indazolyl or benzo[b]thiophen-3-yl, which groups may be substituted with halogen or alkyl (1-3C), R 2 and R 3 independently represent halogen, H, OCH 3 , CH 3 and CF 3 , R 4 , R 5 and R 6 independently represent H, OH, O-alkyl(1-4C), CH 2 OH, NH 2 , dialkyl(1-3C)N, pyrrolidin-1-yl, piperidin-1-yl, morpholin-4-yl or morpholin-4-yl substituted with one or two methyl or methoxymethyl groups, morpholin-4-ylamino, morpholin-4-ylmethyl, imidazol-1-yl, thiomorpholin-4-yl, 1,1-dioxothiomorpholin-4-yl or 3-oxa-8-azabicyclo[3.2.1]oct-8-yl; R 4 and R 5 together may represent a keto, a 1,3-dioxan-2-yl or a 1,3-dioxolan-2-yl group, X represents either O or S, n has the value of 1, 2 or 3, a is the asymmetrical carbon atom 8a, 9a or 10a when n equals 1, 2 or 3 respectively The invention also relates to a method for the preparation of the novel compounds, and to pharmaceutical compositions containing at least one of these compounds as an active ingredient.