Urea derivative and use therefor

Patent metadata

Field	Value
Publication number	US-10280145-B2
Application number	US-201615753567-A
Country	US
Kind code	B2
Filing date	Aug 31, 2016
Priority date	Aug 31, 2015
Publication date	May 7, 2019
Grant date	May 7, 2019

Abstract

A compound has inhibitory activity on Discoidin Domain Receptor 1. A urea derivative is represented by the formula (I) or a pharmaceutically acceptable salt thereof:

wherein, R 1 is trifluoromethyl, trifluoromethoxy, or pentafluorosulfanyl; each R 2 is independently a hydrogen atom or methyl which is optionally substituted by one hydroxyl or one saturated heterocyclyl having four to six ring-forming atoms; R 3 is a hydrogen atom, halogen atom, C 1 -C 3 alkyl, saturated heterocyclyl having four to six ring-forming atoms and optionally having an oxo group, or R 5 O—; and R 4 is phenyl, pyridyl, pyridazinyl, or pyrimidinyl, which phenyl, pyridyl, pyridazinyl, or pyrimidinyl is optionally substituted by one R 6 .

First claim

The invention claimed is:

1. A urea compound represented by Formula (I):

wherein,
R 1 is trifluoromethyl, trifluoromethoxy, or pentafluorosulfanyl;
each R 2 is independently a hydrogen atom or methyl which is optionally substituted by one hydroxyl or one saturated heterocyclyl having four to six ring-forming atoms;
R 3 is a hydrogen atom, halogen atom, C 1 -C 3 alkyl, saturated heterocyclyl having four to six ring-forming atoms and optionally having an oxo group, or R 5 O—;
R 4 is phenyl, pyridyl, pyridazinyl, or pyrimidinyl, which phenyl, pyridyl, pyridazinyl, or pyrimidinyl is optionally substituted by one R 6 ;
m and n are independently 0 or 1;
R 5 is C 1 -C 3 alkyl or saturated heterocyclyl having four to six ring-forming atoms (provided that if a nitrogen atom is included in the ring-forming atoms of R 5 , said nitrogen atom is optionally substituted by acetyl);
R 6 is carbamoyl, phenyl, heteroaryl having five or six ring-forming atoms, saturated heterocyclyl having four to six ring-forming atoms, or (R 7 )R 8 N—; and
each of R 7 and R 8 is independently a hydrogen atom, or C 1 -C 3 alkyl which is optionally substituted by hydroxyl (excluding when m and n are 0; and R 4 is phenyl or pyridyl, which phenyl or pyridyl is substituted by carbamoyl) or a pharmaceutically acceptable salt thereof.

2. The urea compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein
each R 2 is independently a hydrogen atom or hydroxymethyl;
R 3 is a hydrogen atom, morpholinyl, 3-oxopiperazinyl, or R 5 O—;
R 4 is pyridyl or pyrimidinyl, which pyridyl or pyrimidinyl is optionally substituted by one R 6 ;
R 5 is C 1 -C 3 alkyl, 3-oxetanyl, or 3-azetidinyl, 3-pyrrolidinyl, or 4-piperidinyl, which 3-azetidinyl, 3-pyrrolidinyl, or 4-piperidinyl optionally has a nitrogen atom substituted by acetyl; and
R 6 is carbamoyl, pyridyl, morpholinyl, or (R 7 )R 8 N—.

3. The urea compound according to claim 2 , or a pharmaceutically acceptable salt thereof, wherein
R 4 is a group represented by one formula selected from Formulae (IIa) to (IIc), and
m and n are 0:

wherein R 9 is carbamoyl, pyridyl, morpholinyl, or (R 7 )R 8 N—; and the wavy line represents the point to which Formula (I) is linked.

4. The urea compound according to claim 2 , or a pharmaceutically acceptable salt thereof, wherein
R 4 is a group represented by Formula (IId) or (IIe); and
one of m and n is 0 and the other is 1:

wherein R 10 is a hydrogen atom or carbamoyl; and the wavy line represents the point to which Formula (I) is linked.

5. A method of inhibiting Discoidin Domain Receptor 1, comprising administering an effective amount of the urea compound according to claim 1 or a pharmaceutically acceptable salt thereof.

6. A method of inhibiting Discoidin Domain Receptor 1, comprising administering an effective amount of the urea compound according to claim 2 or a pharmaceutically acceptable salt thereof.

7. A method of inhibiting Discoidin Domain Receptor 1, comprising administering an effective amount of the urea compound according to claim 3 or a pharmaceutically acceptable salt thereof.

8. A method of inhibiting Discoidin Domain Receptor 1, comprising administering an effective amount of the urea compound according to claim 4 or a pharmaceutically acceptable salt thereof.

Assignees

• Toray Industries

Inventors

• Nishio Yukihiro
• Kubota Yuko
• Yamamoto Masashi
• Nishimura Yutaka
• Masuda Tomohide
• Tsutsui Hideyuki
• Okimura Keiichi
• Udagawa Syuji
• Kaino Mie
• Meguro Hiroyuki
• Sekiya Yumiko

Classifications

• A61P43/00

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

• A61P35/04

  specific for metastasis · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/4439

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) · CPC title

• C07D405/12

  linked by a chain containing hetero atoms as chain links · CPC title