发明授权
US07094779B2 Piperazine oxime dervatives having NK-1 receptor antagonistic activity
有权
具有NK-1受体拮抗活性的哌嗪肟衍生物
- 专利标题: Piperazine oxime dervatives having NK-1 receptor antagonistic activity
- 专利标题(中): 具有NK-1受体拮抗活性的哌嗪肟衍生物
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申请号: US10480542申请日: 2002-07-03
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公开(公告)号: US07094779B2公开(公告)日: 2006-08-22
- 发明人: Wouter I. Iwema Bakker , Jan H. van Maarseveen , Hein K. A. C. Coolen , Martinus Th. M. Tulp , Arnoldus H. J. Herremans , Andrew C. Mccreary , Gustaaf J. M. van Scharrenburg , Adrianus van den Hoogenband
- 申请人: Wouter I. Iwema Bakker , Jan H. van Maarseveen , Hein K. A. C. Coolen , Martinus Th. M. Tulp , Arnoldus H. J. Herremans , Andrew C. Mccreary , Gustaaf J. M. van Scharrenburg , Adrianus van den Hoogenband
- 申请人地址: NL Weesp
- 专利权人: Solvay Pharmaceuticals B.V.
- 当前专利权人: Solvay Pharmaceuticals B.V.
- 当前专利权人地址: NL Weesp
- 代理机构: Finnegan, Henderson, Farabow, Garrett & Dunner, L.L.P.
- 优先权: EP01202631 20010709
- 国际申请: PCT/EP02/07472 WO 20020703
- 国际公布: WO03/006459 WO 20030123
- 主分类号: A61K31/496
- IPC分类号: A61K31/496 ; C07D403/06 ; C07D413/14 ; C07D471/04
摘要:
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 CH3, CF3, OCH3, halogen, cyano and 5-CF3-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; R1 represents NH2, 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-CH3-piperazinyl; R2 is hydrogen, alkyl (1–4C) or phenyl, or R2 together with (CH2)m wherein m is 1, and the intermediate carbon, nitrogen and oxygen atoms forms an isoxazolyl or a 4,5-dihydroisoxazolyl group; R3 and R4 independently represent hydrogen or methyl, or R3 and R4 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
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