ES2549502T3 - Antagonistas de receptores de gonadoliberina, método de fabricación de los mismos, y composición farmacéutica que los contienen - Google Patents

Antagonistas de receptores de gonadoliberina, método de fabricación de los mismos, y composición farmacéutica que los contienen Download PDF

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ES2549502T3
ES2549502T3 ES10831804T ES10831804T ES2549502T3 ES 2549502 T3 ES2549502 T3 ES 2549502T3 ES 10831804 T ES10831804 T ES 10831804T ES 10831804 T ES10831804 T ES 10831804T ES 2549502 T3 ES2549502 T3 ES 2549502T3
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benzyl
phenyl
ethyl
methyl
piperazin
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Seon Mi Kim
Min Hee Lee
Jae Sun Kim
Hoe Chul Jung
So Young Lee
Soo Min Lee
Eun Jeong Kim
Eui Sun Park
Sung Hoon Park
Bong Yong Lee
Key An Um
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SK Chemicals Co Ltd
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Abstract

Un compuesto, un estereoisómero del mismo o una sal farmacéuticamente aceptable del mismo, seleccionado del grupo que consiste en: 3-((R)-2-amino-2-fenil-etil)-1-(2,6-difluoro-bencil)-5-[4-(2-metoxi-fenil)-piperazin-1-il]-6-metil-1H-pirimidin-2,4- diona; 3-((R)-2-amino-2-fenil-etil)-1-(2,6-difluoro-bencil)-5-[4-(3-metoxi-fenil)-piperazin-1-il]-6-metil-1H-pirimidin-2,4- diona; 3-((R)-2-amino-2-fenil-etil)-5-(4-bencil-piperazin-1-il)-1-(2,6-difluoro-bencil)-6-metil-1H-pirimidin-2,4-diona; 3-((R)-2-amino-2-fenil-etil)-5-[4-(4-cloro-bencil)-piperazin-1-il]-1-(2,6-difluoro-bencil)-6-metil-1H-pirimidin-2,4- diona; 3-((R)-2-amino-2-fenil-etil)-1-(2,6-difluoro-bencil)-5-[4-(2-fluoro-bencil)-piperazin-1-il]-6-metil-1H-pirimidin-2,4- diona; 3-((R)-2-amino-2-fenil-etil)-1-(2,6-difluoro-bencil)-6-metil-5-(4-piridin-2-il-piperazin-1-il)-1H-pirimidin-2,4-diona; 3-((R)-2-amino-2-fenil-etil)-1-(2,6-difluoro-bencil)-5-[4-(3-fluoro-bencil)-piperazin-1-il]-6-metil-1H-pirimidin-2,4- diona; 3-((R)-2-amino-2-fenil-etil)-1-(2,6-difluoro-bencil)-6-metil-5-[4-(4-trifluorometil-bencil)-piperazin-1-il]-1H-pirimidin- 2,4-diona; 3-((R)-2-amino-2-fenil-etil)-5-(4-benzoil-piperazin-1-il)-1-(2,6-difluoro-bencil)-6-metil-1H-pirimidin-2,4-diona; 3-((R)-2-amino-2-fenil-etil)-1-(2,6-difluoro-bencil)-6-metil-5-(4-fenil-piperazin-1-il)-1H-pirimidin-2,4-diona; 20 3-((R)-2-amino-2-fenil-etil)-5-(4-ciclohexilmetil-piperazin-1-il)-1-(2,6-difluoro-bencil)-6-metil-1H-pirimidin-2,4-diona; 3-((R)-2-amino-2-fenil-etil)-1-(2,6-difluoro-bencil)-5-[4-(2-fluoro-fenil)-piperazin-1-il]-6-metil-1H-pirimidin-2,4-diona; 3-((R)-2-amino-2-fenil-etil)-1-(2,6-difluoro-bencil)-5-[4-(2-hidroxi-fenil)-piperazin-1-il]-6-metil-1H-pirimidin-2,4- diona; 3-((R)-2-amino-2-fenil-etil)-1-(2,6-difluoro-bencil)-5-[3-(2-hidroxi-etil)-piperazin-1-il]-6-metil-1H-pirimidin-2,4-diona; 3-((R)-2-amino-2-fenil-etil)-5-(4-benzo[1,3]dioxol-5-ilmetil-piperazin-1-il)-1-(2,6-difluoro-bencil)-6-metil-1Hpirimidin- 2,4-diona; 3-((R)-2-amino-2-fenil-etil)-1-(2,6-difluoro-bencil)-6-metil-5-(3-oxo-piperazin-1-il)-1H-pirimidin-2,4-diona; 3-((R)-2-amino-2-fenil-etil)-1-(2,6-difluoro-bencil)-6-metil-5-[4-(3-trifluorometoxi-bencil)-piperazin-1-il]-1H-pirimidin- 2,4-diona; 3-((R)-2-amino-2-fenil-etil)-1-(2,6-difluoro-bencil)-6-metil-5-piperazin-1-il-1H-pirimidin-2,4-diona; 3-((R)-2-amino-2-fenil-etil)-1-(2,6-difluoro-bencil)-5-{4-[2-(4-metoxi-fenil)-2-oxo-etil]-piperazin-1-il}-6-metil-1Hpirimidin- 2,4-diona; 3-((R)-2-amino-2-fenil-etil)-1-(2,6-difluoro-bencil)-6-metil-5-(4-fenetil-piperazin-1-il)-1H-pirimidin-2,4-diona; 3-((R)-2-amino-2-fenil-etil)-5-(4-bencenosulfonil-piperazin-1-il)-1-(2,6-difluoro-bencil)-6-metil-1H-pirimidin-2,4- diona; 3-((R)-2-amino-2-fenil-etil)-1-(2,6-difluoro-bencil)-5-{4-[2-(2-fluoro-fenil)-etil]-piperazin-1-il}-6-metil-1H-pirimidin- 2,4-diona; 3-((R)-2-amino-2-fenil-etil)-1-(2,6-difluoro-bencil)-5-{4-[2-(2-metoxi-fenil)-etil]-piperazin-1-il}-6-metil-1H-pirimidin- 2,4-diona; 3-((R)-2-amino-2-fenil-etil)-1-(2,6-difluoro-bencil)-5-{4-[2-(4-fluoro-fenil)-etil]-piperazin-1-il}-6-metil-1H-pirimidin- 2,4-diona; 3-((R)-2-amino-2-fenil-etil)-1-(2,6-difluoro-bencil)-5-{4-[2-(3-metoxi-fenil)-etil]-piperazin-1-il}-6-metil-1H-pirimidin- 2,4-diona; 3-((R)-2-amino-2-fenil-etil)-1-(2,6-difluoro-bencil)-6-metil-5-[4-(2-p-tolil-etil)-piperazin-1-il]-1H-pirimidin-2,4-diona; -((R)-2-amino-2-fenil-etil)-1-(2,6-difluoro-bencil)-6-metil-5-{4-[2-(4-nitro-fenil)-etil]-piperazin-1-il}-1H-pirimidin-2,4- diona; 3-((R)-2-amino-2-fenil-etil)-1-(2,6-difluoro-bencil)-6-metil-5-[4-(3-fenil-propil)-piperazin-1-il]-1H-pirimidin-2,4-diona; 3-((R)-2-amino-2-fenil-etil)-1-(2,6-difluoro-bencil)-5-[4-(2,3-dihidrobenzo[1,4]dioxin-2-ilmetil)-piperazin-1-il]-6-metil- 1H-pirimidin-2,4-diona; 3-((R)-2-amino-2-fenil-etil)-5-{4-[2-(2-cloro-fenil)-2-oxo-etil]-piperazin-1-il}-1-(2,6-difluoro-bencil)-6-metil-1Hpirimidin- 2,4-diona; 3-((R)-2-amino-2-fenil-etil)-5-{4-[2-(3-cloro-fenil)-2-oxo-etil]-piperazin-1-il}-1-(2,6-difluoro-bencil)-6-metil-1Hpirimidin- 2,4-diona; 3-((R)-2-amino-2-fenil-etil)-1-(2,6-difluoro-bencil)-6-metil-5-(4-piridin-2-ilmetil-piperazin-1-il)-1H-pirimidin-2,4- diona; 3-((R)-2-amino-2-fenil-etil)-1-(2,6-difluoro-bencil)-6-metil-5-(4-piridin-3-ilmetil-piperazin-1-il)-1H-pirimidin-2,4- diona; 3-((R)-2-amino-2-fenil-etil)-1-(2,6-difluoro-bencil)-6-metil-5-(4-piridin-4-ilmetil-piperazin-1-il)-1H-pirimidin-2,4- diona; 3-((R)-2-amino-2-fenil-etil)-1-(2,6-difluoro-bencil)-5-[4-(2-fluoro-bencenosulfonil)-piperazin-1-il]-6-metil-1Hpirimidin- 2,4-diona; 3-((R)-2-amino-2-fenil-etil)-1-(2,6-difluoro-bencil)-5-[4-(3-fluoro-bencenosulfonil)-piperazin-1-il]-6-metil-1Hpirimidin- 2,4-diona; 3-((R)-2-amino-2-fenil-etil)-1-(2,6-difluoro-bencil)-5-[4-(4-fluoro-bencenosulfonil)-piperazin-1-il]-6-metil-1Hpirimidin- 2,4-diona; 3-((R)-2-amino-2-fenil-etil)-1-(2,6-difluoro-bencil)-6-metil-5-(3-fenil-piperazin-1-il)-1H-pirimidin-2,4-diona; 3-((R)-2-amino-2-fenil-etil)-5-(R)-(3-bencil-piperazin-1-il)-1-(2,6-difluoro-bencil)-6-metil-1H-pirimidin-2,4-diona; 3-((R)-2-amino-2-fenil-etil)-5-(S)-(3-bencil-piperazin-1-il)-1-(2,6-difluoro-bencil)-6-metil-1H-pirimidin-2,4-diona; 2-{4-[3-((R)-2-amino-2-fenil-etil)-1-(2,6-difluoro-bencil)-6-metil-2,4-dioxo-1,2,3,4-tetrahidro-pirimidin-5-il]-piperazin- 1-ilmetil}-benzonitrilo; 3-{4-[3-((R)-2-amino-2-fenil-etil)-1-(2,6-difluoro-bencil)-6-metil-2,4-dioxo-1,2,3,4-tetrahidro-pirimidin-5-il]-piperazin- 1-ilmetil}-benzonitrilo; 4-{4-[3-((R)-2-amino-2-fenil-etil)-1-(2,6-difluoro-bencil)-6-metil-2,4-dioxo-1,2,3,4-tetrahidro-pirimidin-5-il]-piperazin- 1-ilmetil}-benzonitrilo; 3-((R)-2-amino-2-fenil-etil)-1-(2,6-difluoro-bencil)-5-[4-(3-metoxi-bencil)-piperazin-1-il]-6-metil-1H-pirimidin-2,4- diona; 3-((R)-2-amino-2-fenil-etil)-1-(2,6-difluoro-bencil)-5-[4-(4-metoxi-bencil)-piperazin-1-il]-6-metil-1H-pirimidin-2,4- diona; 3-((R)-2-amino-2-fenil-etil)-5-[4-(2-cloro-bencil)-piperazin-1-il]-1-(2,6-difluoro-bencil)-6-metil-1H-pirimidin-2,4- diona; 3-((R)-2-amino-2-fenil-etil)-5-[4-(3-cloro-bencil)-piperazin-1-il]-1-(2,6-difluoro-bencil)-6-metil-1H-pirimidin-2,4- diona; 3-((R)-2-amino-2-fenil-etil)-1-(2,6-difluoro-bencil)-6-metil-5-[4-(2-nitro-bencil)-piperazin-1-il]-1H-pirimidin-2,4-diona; 3-((R)-2-amino-2-fenil-etil)-1-(2,6-difluoro-bencil)-6-metil-5-[4-(3-nitro-bencil)-piperazin-1-il]-1H-pirimidin-2,4-diona; 3-((R)-2-amino-2-fenil-etil)-1-(2,6-difluoro-bencil)-6-metil-5-[4-(4-nitro-bencil)-piperazin-1-il]-1H-pirimidin-2,4-diona; 3-((R)-2-amino-2-fenil-etil)-1-(2,6-difluoro-bencil)-6-metil-5-[4-(2-metil-bencil)-piperazin-1-il]-1H-pirimidin-2,4- diona; 3-((R)-2-amino-2-fenil-etil)-1-(2,6-difluoro-bencil)-6-metil-5-[4-(4-metil-bencil)-piperazin-1-il]-1H-pirimidin-2,4- diona;
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