Imidazolylamide derivative

Patent metadata

Field	Value
Publication number	US-10898469-B2
Application number	US-201716079952-A
Country	US
Kind code	B2
Filing date	Feb 23, 2017
Priority date	Feb 26, 2016
Publication date	Jan 26, 2021
Grant date	Jan 26, 2021

Abstract

The present invention pertains to an imidazolylamide derivative represented by formula (1) that exhibits an exceptional suppressive effect on cancer cell sphere formation ability and that is useful as an antitumor agent that can be administered orally, or a pharmacologically acceptable salt thereof. [In the formula, ring Q 1 represents a C 6-10 aryl group or the like; m represents 0, 1, 2, 3, 4, or 5; R 3 , independently when multiple, represent(s) a halogen atom or the like; R 1 and R 2 independently represent a hydrogen atom or the like; W 1 represents a C 1-4 alkylene group (said group may be substituted by 1-3 fluorine atoms or C 3-7 cycloalkyls); W 2 represents —NR 4a C(O)— or the like (where R 4a represents a hydrogen atom or C 1-6 alkyl group); and ring Q 2 represents a C 6-10 arylgroup or the like]

First claim

What is claimed is:

1. A compound of Formula (1):

wherein Q 1 is C 6-10 aryl, C 6-10 aryloxy, C 6-10 arylthio, C 3-10 cycloalkyl, or 5- to 10-membered heteroaryl;
m is 0, 1, 2, 3, 4, or 5;
each R 3 is independently selected from:

(1) halogen,
(2) optionally-substituted C 1-6 alkyl,
(3) optionally-substituted C 1-6 alkoxy,
(4) optionally-substituted amino,
(5) optionally-substituted C 6-10 aryl,
(6) optionally-substituted C 6-10 aryloxy,
(7) optionally-substituted 5- to 10-membered heteroaryl,
(8) optionally-substituted C 1-6 alkoxy-carbonyl,
(9) optionally-substituted aminocarbonyl,
(10) optionally-substituted C 1-6 alkyl-carbonyl,
(11) optionally-substituted C 1-6 alkylsulfonyl,
(12) optionally-substituted C 1-6 alkyl-carbonylamino,
(13) optionally-substituted C 1-6 alkylsulfonylamino,
(14) optionally-substituted C 1-6 alkoxy-carbonylamino,
(15) optionally-substituted C 1-6 alkyl-carbonyloxy,
(16) hydroxy,
(17) cyano,
(18) optionally-substituted amino sulfonyl, and
(19) optionally-substituted C 3-10 cycloalkyl;
provided that when two R a s bind to any of the adjacent carbon atoms on Ring Q 1 , the R 3 groups may combine together with the carbon atoms to which they are attached to form a 5- to 8-membered saturated carbocyclic ring or non-aromatic heterocyclic ring, each of which is optionally substituted with 1 to 2 groups independently selected from the group consisting of halogen, C 1-6 alkyl, and C 1-6 alkoxy,
R 1 and R 2 are each independently hydrogen, halogen, or C 1-6 alkyl which is optionally substituted with 1 to 3 independently selected halogen atoms;
W 1 is C 1-4 alkylene which is optionally substituted with 1 to 3 fluorine atoms or C 3-7 cycloalkyl;
W 2 -Q 2 is —NHC(O)—CH═CH-Q 2 ;
Ring Q 2 is:

(1) phenyl which is optionally substituted with 1 to 4 groups independently selected from the group consisting of:
(a) cyano;
(b) C 1-6 alkyl which is optionally substituted with 1 to 3 groups independently selected halogen and hydroxy;
(c) amino which is optionally substituted with 1 to 2 independently selected C 1-6 alkyl groups, wherein each alkyl group is optionally substituted with 1 to 3 independently selected halogen atoms;
(d) C 1-6 alkyl-carbonylamino wherein the alkyl moiety of the alkyl-carbonylamino is optionally substituted with 1 to 3 groups independently selected from halogen, hydroxy, and C 1-6 alkoxy;
(e) C 1-6 alkoxy which is optionally substituted with 1 to 3 groups independently selected from halogen, hydroxy, and C 1-6 alkoxy,
(f) phenoxy which is optionally substituted with 1 to 4 groups independently selected from the group consisting of halogen, C 1-6 alkyl, and C 1-6 alkoxy, and
(g) halogen atom;

or
(2) pyridyl which is optionally substituted with 1 to 4 groups independently selected from the group consisting of:
(a) cyano,
(b) C 1-6 alkyl which is optionally substituted with 1 to 3 independently selected halogen atoms,
(c) amino which is optionally substituted with 1 to 2 independently selected C 1-6 alkyl groups, wherein each alkyl group is optionally substituted with 1 to 3 independently selected halogen atoms, and
(d) C 1-6 alkyl-carbonylamino wherein the alkyl moiety of the alkyl-carbonylamino is optionally substituted with 1 to 3 groups independently selected from halogen, hydroxy, and C 1-6 alkoxy;

or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein Q 1 is phenyl.

3. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein m is 3 or 4.

4. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 3 is independently selected from
(1) halogen,
(2) C 1-6 alkyl which is optionally substituted with 1 to 3 groups independently selected from the group consisting of halogen, hydroxy, and C 1-6 alkoxy,
(3) C 1-6 alkoxy which is optionally substituted with 1 to 3 groups independently selected from the group consisting of halogen, hydroxy, C 1-6 alkoxy, and phenyl,
(4) amino which is optionally substituted with 1 to 2 independently selected C 1-6 alkyl groups,
(5) C 6-10 aryl which is optionally substituted with 1 to 4 groups independently selected from the group consisting of halogen, C 1-6 alkyl, and C 1-6 alkoxy,
(6) C 6-10 aryloxy which is optionally substituted with 1 to 4 groups independently selected from the group consisting of halogen, C 1-6 alkyl, and C 1-6 alkoxy,
(7) 5- to 10-membered heteroaryl which is optionally substituted with 1 to 4 groups independently selected from the group consisting of halogen, C 1-6 alkyl, and C 1-6 alkoxy, and
(8) C 1-6 alkoxy-carbonyl.

5. The compound according to claim 4 , or a pharmaceutically acceptable salt thereof, wherein each R 3 is independently a halogen atom or C 1-6 alkyl which is optionally substituted with 1 to 3 independently selected halogen atoms.

6. The compound according to claim 4 , or a pharmaceutically acceptable salt thereof, wherein any or all of R 3 is fluorine.

7. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein W 1 is methylene.

8. The compound according to claim 7 , wherein Ring Q 2 is phenyl substituted with 1 to 3 groups independently selected from the group consisting of C 1-6 alkoxy which is optionally substituted with 1 to 3 groups independently selected from halogen, hydroxy, and C 1-6 alkoxy, and C 1-6 alkyl-carbonylamino, wherein the alkyl moiety of the alkyl-carbonylamino is optionally substituted with 1 to 3 groups independently selected from halogen, hydroxy, and C 1-6 alkoxy.

9. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein Ring Q 2 is phenyl substituted with 1 to 3 C 1-6 alkoxy groups, each of which is optionally substituted with 1 to 3 groups independently selected from halogen, hydroxy, and C 1-6 alkoxy.

10. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein both R 1 and R 2 are hydrogen.

11. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, which has the structure of Formula (1a):

wherein Ring Q 1a is trifluorophenyl or trifluoromethylphenyl;
Ring Q 2a is phenyl substituted with 1 to 3 groups independently selected from the group consisting of hydroxy, C 1-6 alkoxy which is optionally substituted with 1 to 3 groups independently selected from halogen, hydroxy, and C 1-6 alkoxy, and C 1-6 alkyl-carbonylamino, wherein the alkyl moiety of the alkyl-carbonylamino is optionally substituted with 1 to 3 groups independently selected from halogen, hydroxy, and C 1-6 alkoxy, and
W 2a -Q 2a is —NHC(O)—CH═CH-Q 2a ;

or a pharmaceutically acceptable salt thereof.

12. The compound according to claim 11 , or a pharmaceutically acceptable salt thereof, wherein Ring Q 1a is trifluorophenyl.

13. The compound according to claim 1 , which is selected from the following compounds:
(2E)-3-[4-(acetylamino)phenyl]-N-[1-(3-chlorobenzyl)-1H-imidazol-4-yl]prop-2-enamide,
(2E)-N-[1-(3-chlorobenzyl)-1H-imidazol-4-yl]-3-(pyridin-3-yl)prop-2-enamide,
(2E)-N-[1-(3-chlorobenzyl)-1H-imidazol-4-yl]

Assignees

• Sumitomo Dainippon Pharma Co Ltd

Inventors

• Ban Hitoshi
• Kusagi Manabu
• Tojo Shingo
• Otsubo Tsuguteru
• Sugaru Eiji
• Yamaguchi Hiroki
• Sawada Nobuyuki
• Li Chiang Jia

Classifications

• C07D403/12 Primary

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

• C07D233/88

  Nitrogen atoms, e.g. allantoin · CPC title

• C07D233/90

  Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals · CPC title

• C07D409/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title

• C07D417/12

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