Pharmaceutical composition having pyrimidine compound as active ingredient

Patent metadata

Field	Value
Publication number	US-2016199371-A1
Application number	US-201414914955-A
Country	US
Kind code	A1
Filing date	Aug 27, 2014
Priority date	Aug 28, 2013
Publication date	Jul 14, 2016
Grant date	—

Abstract

[Problem]
A pharmaceutical composition for treating FGFR4-related cancer, FGF 19-related cancer, or FGF19 gene amplification-positive liver cancer is provided.
[Means for Solution]
The present inventors have investigated a compound having an inhibitory action on FGFR4, and found that a specific pyrimidine compound has an inhibitory action on FGFR4 and a pharmaceutical composition having the compound as an active ingredient has an effect of treating FGFR4-related cancer, in another embodiment, FGF19-related cancer, and in still another embodiment, FGF19 gene amplification-positive liver cancer, thereby completing the present invention.

First claim

1 - 8 . (canceled)

9 . A pharmaceutical composition for treating a FGFR4-related cancer, comprising 5-[(2,6-difluoro-3,5-dimethoxybenzyl)oxy]-N-{3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}pyrimidin-2-amine, 2-[4-({5-[(2,6-difluoro-3,5-dimethoxybenzyl)oxy]pyrimidin-2-yl}amino)-1H-pyrazol-1-yl]ethanol, (2R)-3-[4-({5-[(2,6-difluoro-3,5-dimethoxybenzyl)oxy]pyrimidin-2-yl}amino)-1H-pyrazol-1-yl]propane-1,2-diol, 5-[(2,6-difluoro-3,5-dimethoxybenzyl)oxy]-N-[4-(4-methylpiperazin-1-yl)phenyl]pyrimidin-2-amine or 5-[(2,6-difluoro-3,5-dimethoxybenzyl)oxy]-N-{1-methyl-5-[(4-methylpiperazin-1-yl)methyl]-1H-pyrazol-3-yl}pyrimidin-2-amine, or a pharmaceutically acceptable salt thereof, and an excipient.

10 . The pharmaceutical composition according to claim 9 , wherein the FGFR4-related cancer is FGF19-related cancer.

11 . The pharmaceutical composition according to claim 9 , wherein the FGFR4-related cancer is FGF19 gene amplification-positive liver cancer.

12 . The pharmaceutical composition according to claim 9 , wherein the pharmaceutical composition comprises 2-[4-({5-[(2,6-difluoro-3,5-dimethoxybenzyl)oxy]pyrimidin-2-yl}amino)-1H-pyrazol-1-yl]ethanol or a pharmaceutically acceptable salt thereof, and an excipient.

13 . The pharmaceutical composition according to claim 10 , wherein the pharmaceutical composition comprises 2-[4-({5-[(2,6-difluoro-3,5-dimethoxybenzyl)oxy]pyrimidin-2-yl}amino)-1H-pyrazol-1-yl]ethanol or a pharmaceutically acceptable salt thereof, and an excipient.

14 . The pharmaceutical composition according to claim 11 , wherein the pharmaceutical composition comprises 2-[4-({5-[(2,6-difluoro-3,5-dimethoxybenzyl)oxy]pyrimidin-2-yl}amino)-1H-pyrazol-1-yl]ethanol or a pharmaceutically acceptable salt thereof, and an excipient.

15 . A method for treating a FGFR4-related cancer, comprising administering to a subject an effective amount of 5-[(2,6-difluoro-3,5-dimethoxybenzyl)oxy]-N-{3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}pyrimidin-2-amine, 2-[4-({5-[(2,6-difluoro-3,5-dimethoxybenzyl)oxy]pyrimidin-2-yl}amino)-1H-pyrazol-1-yl]ethanol, (2R)-3-[4-({5-[(2, 6-difluoro-3,5-dimethoxybenzyl)oxy]pyrimidin-2-yl}amino)-1H-pyrazol-1-yl]propane-1,2-diol, 5-[(2,6-difluoro-3,5-dimethoxybenzyl)oxy]-N-[4-(4-methylpiperazin-1-yl)phenyl]pyrimidin-2-amine or 5-[(2,6-difluoro-3,5-dimethoxybenzyl)oxy]-N-{1-methyl-5-[(4-methylpiperazin-1-yl)methyl]-1H-pyrazol-3-yl}pyrimidin-2-amine, or a pharmaceutically acceptable salt thereof.

16 . The method according to claim 15 , wherein the FGFR4-related cancer is FGF19-related cancer.

17 . The method according to claim 15 , wherein the FGFR4-related cancer is FGF19 gene amplification-positive liver cancer.

18 . The method according to claim 15 , wherein the method comprises administering an effective amount of 2-[4-({5-[(2,6-difluoro-3,5-dimethoxybenzyl)oxy]pyrimidin-2-yl}amino)-1H-pyrazol-1-yl]ethanol or a pharmaceutically acceptable salt thereof.

19 . The method according to claim 16 , wherein the method comprises administering an effective amount of 2-[4-({5-[(2,6-difluoro-3,5-dimethoxybenzyl)oxy]pyrimidin-2-yl}amino)-1H-pyrazol-1-yl]ethanol or a pharmaceutically acceptable salt thereof.

20 . The method according to claim 17 , wherein the method comprises administering an effective amount of 2-[4-({5-[(2,6-difluoro-3,5-dimethoxybenzyl)oxy]pyrimidin-2-yl}amino)-1H-pyrazol-1-yl]ethanol or a pharmaceutically acceptable salt thereof, and an excipient.

Assignees

• Astellas Pharma Inc
• Astellas Pharma Inc

Inventors

• Futami Takashi
• Takeshita Rumi

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P1/16

  for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics · CPC title

• A61K31/506 Primary

  not condensed and containing further heterocyclic rings · CPC title