1,4-disubstituted imidazole derivative

Patent metadata

Field	Value
Publication number	US-10807945-B2
Application number	US-201615507188-A
Country	US
Kind code	B2
Filing date	Jun 21, 2016
Priority date	Jun 22, 2015
Publication date	Oct 20, 2020
Grant date	Oct 20, 2020

Abstract

The present invention provides a 1,4-disubstituted imidazole derivative of formula (1′) wherein ring Q 1 is optionally-substituted C 6-10 aryl group, etc.; R 1 and R 2 are independently hydrogen atom, etc.; W 1 is optionally-substituted C 1-4 alkylene group; W 2 is —NR 3a C(O)— wherein R 3a is hydrogen atom or C 1-6 alkyl group, etc.; ring Q 2 is 5- to 10-membered heteroaryl group, etc.; W 3 is optionally-substituted C 1-4 alkylene group, etc.; n is 1, 2, 3, 4, or 5; R 4 is independently halogen atom, optionally-substituted C 1-6 alkyl group, etc.; R 5 is hydroxy group, etc.; and a pharmacologically acceptable salt thereof, which have a potent inhibitory effect on the sphere-forming capacity of cancer cells and are useful as an orally-available anti-tumor agent.

First claim

The invention claimed is:

1. A compound of formula (1′):

or a pharmaceutically acceptable salt thereof, wherein ring Q′ is optionally-substituted C 6-10 aryl group, optionally-substituted C 3-10 cycloalkyl group, or optionally-substituted 5- to 10-membered heteroaryl group;
R 1 and R 2 are independently hydrogen atom, halogen atom, or C 1-6 alkyl group which may be optionally substituted with the same or different 1 to 3 halogen atoms;
W 1 is optionally-substituted C 1-4 alkylene group;
W 2 -Q 2 is —NR 3a C(O)-Q 2 , —NR 3a C(O)O-Q 2 , —NR 3a C(O)OCH 2 -Q 2 , —NR 3a C(O)NR 3b -Q 2 , —NR 3a C(O)NR 3b CH 2 -Q 2 , —NR 3a C(O)CH 2 O-Q 2 , —NR 3a C(O)CH 2 -Q 2 , —NR 3a C(O)CH 2 CH 2 -Q 2 , —C(O)NR 3a -Q 2 , —C(O)NR 3a CH 2 -Q 2 , —C(O)NR 3a CH 2 CH 2 -Q 2 , or —NR 3a C(O)—CR 3c ═CR 3d -Q 2 wherein R 3a and R 3b are independently hydrogen atom or C 1-6 alkyl group; and R 3c and R 3d are independently hydrogen atom, fluorine atom, or C 1-6 alkyl group;
ring Q 2 is 5- to 10-membered heteroaryl group;
W 3 is optionally-substituted C 1-4 alkylene group, optionally-substituted C 3-4 alkenylene group, or optionally-substituted C 3-4 alkynylene group;
n is 1, 2, 3, 4, or 5;
R 4 is, independently when two or more exist, hydrogen atom, halogen atom, optionally-substituted C 1-6 alkyl group, optionally-substituted C 1-6 alkoxy group, optionally-substituted C 3-10 cycloalkyl group, optionally-substituted C 2-6 alkenyl group, optionally-substituted C 2-6 alkynyl group, cyano group, optionally-substituted C 1-6 alkyl-carbonyl group, optionally-substituted C 1-6 alkyl sulfonyl group, optionally-substituted C 1-6 alkoxy-carbonyl group, optionally-substituted C 1-6 alkyl-carbonylamino group, optionally-substituted C 1-6 alkylsulfonylamino group, optionally-substituted C 1-6 alkoxy-carbonylamino group, optionally-substituted C 1-6 alkyl-carbonyloxy group, optionally-substituted amino group, optionally-substituted aminocarbonyl group, optionally-substituted aminosulfonyl group, optionally-substituted 5- or 6-membered cyclic amino group, optionally-substituted 5- or 6-membered cyclic aminocarbonyl group, nitro group, or carboxyl group;
when R 4 and W 3 are attached to the adjacent carbon atoms on ring Q 2 , they may be combined with the carbon atoms to form 5- to 8-membered cycloalkane ring; and
R 5 is
(1) hydroxy group,
(2) C 1-6 alkoxy group which may be optionally substituted with the same or different 1 to 3 groups independently selected from the group consisting of halogen atom, hydroxy, C 1-6 alkoxy, and C 6-10 aryl which may be optionally substituted with the same or different 1 to 4 groups independently selected from the group consisting of halogen atom, C 1-6 alkyl, and C 1-6 alkoxy,
(3) amino group which may be optionally substituted with the same or different 1 to 2 C 1-6 alkyl groups, or
(4) C 1-6 alkyl-carbonylamino group wherein the alkyl moiety thereof may be optionally substituted with the same or different 1 to 3 halogen atoms.

2. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein ring Q 1 is optionally-substituted C 6-10 aryl group, optionally-substituted C 3-10 cycloalkyl group, or optionally-substituted 5- to 10-membered heteroaryl group;
R 1 and R 2 are independently hydrogen atom, halogen atom, or C 1-6 alkyl group which may be optionally substituted with the same or different 1 to 3 halogen atoms;
W 1 is optionally-substituted C 1-4 alkylene group;
W 2 -Q 2 is —NR 3a C(O)-Q 2 , —NR 3a C(O)O-Q 2 , —NR 3a C(O)OCH 2 -Q 2 , —NR 3a C(O)NR 3b -Q 2 , —NR 3a C(O)NR 3b CH 2 -Q 2 , —NR 3a C(O)CH 2 O-Q 2 , —NR 3a C(O)CH 2 -Q 2 , —NR 3a C(O)CH 2 CH 2 -Q 2 , —C(O)NR 3a -Q 2 , —C(O)NR 3a CH 2 -Q 2 , or —C(O)NR 3a CH 2 CH 2 -Q 2 wherein R 3a and R 3b are independently hydrogen atom or C 1-6 alkyl group;
ring Q 2 is 5- to 10-membered heteroaryl group;
W 3 is optionally-substituted C 1-4 alkylene group, optionally-substituted C 3-4 alkenylene group, or optionally-substituted C 3-4 alkynylene group;
n is 1, 2, 3, 4, or 5;
R 4 is, independently when two or more exist, hydrogen atom, halogen atom, optionally-substituted C 1-6 alkyl group, optionally-substituted C 1-6 alkoxy group, optionally-substituted C 3-10 cycloalkyl group, optionally-substituted C 2-6 alkenyl group, optionally-substituted C 2-6 alkynyl group, cyano group, or optionally-substituted amino group;
when R 4 and W 3 are attached to the adjacent carbon atoms on ring Q 2 , they may be combined with the carbon atoms to form 5- to 8-membered cycloalkane ring; and
R 5 is
(1) hydroxy group,
(2) C 1-6 alkoxy group which may be optionally substituted with the same or different 1 to 3 groups independently selected from the group consisting of halogen atom, hydroxy, C 1-6 alkoxy, and C 6-10 aryl which may be optionally substituted with the same or different 1 to 4 groups independently selected from the group consisting of halogen atom, C 1-6 alkyl, and C 1-6 alkoxy,
(3) amino group which may be optionally substituted with the same or different 1 to 2 C 1-6 alkyl groups, or
(4) C 1-6 alkyl-carbonylamino group wherein the alkyl moiety thereof may be optionally substituted with the same or different 1 to 3 halogen atoms.

3. The compound according to claim 1 or a pharmaceutically acceptable salt thereof wherein ring Q 1 is
(1) C 6-10 aryl group which may be optionally substituted with the same or different 1 to 5 groups independently selected from the group consisting of
(a) halogen atom,
(b) C 1-6 alkyl which may be optionally substituted with the same or different 1 to 3 groups independently selected from the group consisting of halogen atom, hydroxy, and C 1-6 alkoxy,
(c) C 1-6 alkoxy which may be optionally substituted with the same or different 1 to 3 groups independently selected from the group consisting of halogen atom, hydroxy, and C 1-6 alkoxy,
(d) cyano,
(e) C 6-10 aryl which may be optionally substituted with the same or different 1 to 4 groups independently selected from the group consisting of halogen atom, C 1-6 alkyl, and C 1-6 alkoxy,
(f) 5- or 6-membered heteroaryl which may be optionally substituted with the same or different 1 to 4 groups independently selected from the group consisting of halogen atom, C 1-6 alkyl, and C 1-6 alkoxy,
(g) C 6-10 aryloxy which may be optionally substituted with the same or different 1 to 4 groups independently selected from the group consisting of halogen atom, C 1-6 alkyl, and C 1-6 alkoxy,
(h) hydroxy,
(i) amino which may be optionally substituted with the same or different 1 to 2 C 1-6 alkyl groups,
(j) aminocarbonyl wherein the amino moiety thereof may be optionally substituted with the same or different 1 to 2 C 1-6 alkyl groups,
(k) C 1-6 alkoxy-carbonyl wherein the alkoxy moiety thereof may be optionally substituted with the same or different 1 to 3 groups independently selected from the group consisting of halogen atom, hydroxy, and C 1-6 alkoxy,
(l) C 1-6 alkyl-carbonyl wherein the alkyl moiety thereof may be optionally substituted with the same or different 1 to 3 groups independently selected from the group consisting of halogen atom, hydroxy, and C 1-6 alkoxy,
(m) C 1-6 alkylsulfonyl wherein the alkyl moiety thereof may be optionally substituted with the same or different 1 to 3 groups independently selected from the group consisting of halogen atom, hydroxy, and C 1-6 alkoxy,
(n) C 1-6 alkyl-carbonylamino wherein the alkyl moiety thereof may be optionally substituted with the same or different 1 to 3 groups independently selected from the group consisting of halogen at

Assignees

• Sumitomo Dainippon Pharma Co Ltd

Inventors

• Ban Hitoshi
• Kusagi Manabu
• Tojo Shingo
• Hasegawa Futoshi
• Hashizume Miki

Classifications

• C07D413/12 Primary

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

• A61K31/422 Primary

  not condensed and containing further heterocyclic rings · CPC title

• C07D417/12

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

• C07D403/12

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

• C07D401/12 Primary

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