Piperazine oxime dervatives having NK-1 receptor antagonistic activity

US7094779B2 · kind B2 · utility

Assignee

• Solvay Pharmaceuticals, B.V. · NL

Inventors

• Wouter Bakker · Weesp, NL
• Jan Herman van Maarseveen · Amersfoort, NL
• Hein K. A. C. Coolen · Weesp, NL
• Martinus Th. M. Tulp · Weesp, NL
• Arnoldus H. J. Herremans · Weesp, NL
• Andrew McCreary · Weesp, NL
• Gustaaf J. M. Van Scharrenburg · Weesp, NL
• Adrianus Van Den Hoogenband · Weesp, NL

Key dates

• Filing date: Jul 3, 2002
• Grant date: Aug 22, 2006
• Expiry date: Sep 4, 2022

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D471/04
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

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 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 comp…