Bicyclylaryl-aryl-amine compounds and their use

1. A compound of the following formula, or a pharmaceutically acceptable salt thereof:

wherein:

each of —R C1 , —R C2 , —R C3 , and —R C4 is independently —H or -Q C ;

—R A3 is —H;

—R A6 is —H;

—R B3 is —H;

—R B5 is -Q B5 ;

—R B6 is —O—R QB6 ;

-Q B5 is —CN;

-Q B6 is —O—R QB6 ;

wherein:

—R QB6 is independently:

—R 4A1 ,

-L 4A -OH, -L 4A -OR 4A1 ,

-L 4A -NH 2 , -L 4A -NHR 4A1 , -L 4A -NR 4A1 2 , or -L 4A -NR 4A2 R 4A3 ;

wherein:

each -L 4A - is saturated aliphatic C 2-6 alkylene;

each —NR 4A2 R 4A3 is independently azetidino, pyrrolidino, imidazolidino, pyrazolidino, piperidino, piperazino, morpholino, azepino, diazepino, or oxazepino, and is optionally substituted with one or more groups selected from C 1-3 alkyl, —CF 3 , and —F;

each —R 4A1 is independently:

—R 4B1 , —R 4B4 , —R 4B6 , —R 4B7 , —R 4B8 ,

-L 4B -R 4B4 , -L 4B -R 4B6 , -L 4B -R 4B7 , or -L 4B -R 4B8 ;

each —R 4B1 is saturated aliphatic C 1-6 alkyl;

each —R 4B4 is saturated C 3-6 cycloalkyl;

each —R 4B6 is non-aromatic C 3-8 heterocyclyl;

each —R 4B7 is phenyl;

each —R 4B8 is C 5-6 heteroaryl;

each -L 4B - is saturated aliphatic C 1-3 alkylene;

wherein:

each —R 4B4 , —R 4B6 , —R 4B7 , and —R 4B8 is optionally substituted with one or more substituents —R 4C1 and/or one or more substituents —R 4C2 ;

each —R 4B1 and -L 4B - is optionally substituted with one or more substituents —R 4C2 ;

wherein:

each —R 4C1 is independently saturated aliphatic C 1-4 alkyl, phenyl, or benzyl;

each —R 4C2 is independently:

—F, —Cl, —Br, —I,

—CF 3 , —OCF 3 ,

—OH, -L 4D -OH, —O-L 4D -OH,

—OR 4D1 , -L 4D -OR 4D1 , —O-L 4D -OR 4D1 ,

—SH, —SR 4D1 ,

—CN,

—NO 2 ,

—NH 2 , —NHR 4D1 , —NR 4D1 2 , —NR 4D2 R 4D3 ,

-L 4D -NH 2 , -L 4D -NHR 4D1 , -L 4D -NR 4D1 2 , -L 4D -NR 4D2 R 4D3 ;

—C(═O)OH, —C(═O)OR 4D1 ,

—C(═O)NH 2 , —C(═O)NHR 4D1 , —C(═O)NR 4D1 2 , or —C(═O)NR 4D2 R 4D3 ;

wherein:

each —R 4D1 is independently saturated aliphatic C 1-4 alkyl, phenyl, or benzyl;

each -L 4D - is saturated aliphatic C 1-5 alkylene; and

each —NR 4D2 R 4D3 is independently pyrrolidino, piperidino, piperazino, or morpholino, and is optionally substituted with one or more groups selected from C 1-3 alkyl, —CF 3 , and —F;

and wherein:

each -Q C is independently selected from:

—R 2A1 , —F, —Cl, —Br, —I, —CF 3 , —OCF 3 ,

—OH, -L 2A -OH, —O-L 2A -OH, —NH-L 2A -OH,

—OR 2A1 , L 2A -OH, —O-L 2A -OH, —NH-L 2A -OH,

—NH 2 , —NHR 2A , —NR 2A1 3 , —NR 2A2 R 2A3 ,

—NH 2 , —NHR 2A1 , NR 2A1 2 , -L 2A -NR 2A1 2 , -L 2A -NR 2A2 R 2A3 ,

-L 2A -NH 2 , -L 2A -NHR 2A1 , -L 2A -NR 2A1 2 , -L 2A -NR 2A2 R 2A3 ,

—O-L 2A -NH 2 , —O-L 2A -NHR 2A1 , —O-L 2A -NR 2A1 2 , —O-L 2A -NR 2A2 R 2A3 ,

—NH-L 2A -NH 2 , —NH-L 2A -NHR 2A1 , —NH-L 2A -NR 2A1 2 , —NH-L 2A -NR 2A2 R 2A3 ,

—C(═O)NH 2 , —C(═O)NHR 2A1 , —C(═O)NR 2A1 2 , —C(═O)NR 2A2 R 2A3 ,

—C(═O)NH-L 2A -OH, —C(═O)NH-L 2A -OR 2A1 ,

—C(═O)NH-L 2A -NH 2 , —C(═O)NH-L 2A -NHR 2A1 ,

—C(═O)NH-L 2A -NR 2A1 2 , —C(═O)NH-L 2A -NR 2A2 R 2A3 ,

—NHC(═O)R 2A1 , —NR 2A1 C(═O)R 2A1 ,

—NHC(═O)-L 2A -OH, —NHC(═O)-L 2A -OR 2A1 ,

—NHC(═O)-L 2A -NH 2 , —NHC(═O)-L 2A -NHR 2A1 ,

—NHC(═O)-L 2A -NR 2A1 2 , and —NHC(═O)-L 2A -NR 2A2 R 2A3 ;

wherein:

each -L 2A - is saturated aliphatic C 1-5 alkylene;

each —NR 2A2 R 2A3 is independently pyrrolidino, piperidino, piperazino, or morpholino, and is optionally substituted with one or more groups selected from C 1-3 alkyl, —CF 3 , and —F;

each —R 2A1 is independently —R 2B1 , —R 2B7 , or -L 2B -R 2B7 ;

each —R 2B1 is saturated aliphatic C 1-6 alkyl;

each —R 2B7 is phenyl;

each -L 2B - is saturated aliphatic C 1-3 alkylene;

wherein:

each —R 2B7 is optionally substituted with one or more substituents —R 2C1 and/or one or more substituents —R 2C2 ;

each —R 2B1 and -L 2B - is optionally substituted with one or more substituents —R 2C2 ;

wherein:

each —R 2C1 is independently saturated aliphatic C 1-4 alkyl, phenyl, or benzyl;

each —R 2C2 is independently:

—F, —Cl, —Br, —I,

—CF 3 , —OCF 3 ,

—OH, -L 2D -OH, —O-L 2D -OH,

—OR 2D1 , -L 2D -OR 2D1 , —O-L 2D -OR 2D1 ,

—SH, —SR 2D1 ,

—CN,

—NO 2 ,

—NH 2 , —NHR 2D1 , —NR 2D1 2 , —NR 2D2 R 2D3 ,

-L 2D -NH 2 , -L 2D -NHR 2D1 , -L 2D -NR 2D1 2 , -L 2D -NR 2D2 R 2D3 ,

—C(═O)OH, —C(═O)OR 2D1 ,

—C(═O)NH 2 , —C(═O)NHR 2D1 , —C(═O)NR 2D1 2 , or —C(═O)NR 2D2 R 2D3 ;

wherein:

each —R 2D1 is independently saturated aliphatic C 1-4 alkyl, phenyl, or benzyl;

each -L 2D - is saturated aliphatic C 1-5 alkylene; and

each —NR 2D2 R 2D3 is independently pyrrolidino, piperidino, piperazino, or morpholino, and is optionally substituted with one or more groups selected from C 1-3 alkyl, —CF 3 , and —F.

2. A compound according to claim 1 , wherein —R C1 is -Q C ; and each of —R C2 , —R C3 , and —R C4 is —H.

3. A compound according to claim 2 , wherein —R QB6 is independently -L 4A -NH 2 , -L 4A -NHR 4A1 , -L 4A -NR 4A1 2 , or -L 4A -NR 4A2 R 4A3 .

4. A compound according to claim 2 , wherein —R QB6 is —R 4A1 .

5. A compound according to claim 3 , wherein each —NR 4A2 R 4A3 , if present, is independently pyrrolidino, piperidino, piperazino, or, morpholino, and is optionally substituted with one or more groups selected from C 1-3 alkyl, —CF 3 , and —F.

6. A compound according to claim 4 , wherein —R 4A1 is independently —R 4B6 or -L 4B -R 4B6 .

7. A compound according to claim 6 , wherein each —R 4B6 is independently pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, tetrahydrofuranyl, tetrahydropyranyl, oxazepanyl, 8-aza-bicyclo[3.2.1]octanyl, or quinuclidinyl, and is optionally substituted with one or more substituents —R 4C1 and/or one or more substituents —R 4C2 .

8. A compound according to claim 2 , wherein each -Q C is independently selected from:

—R 2A1 , —F, —Cl, —Br, —I, —CF 3 , —OCF 3 ,

—OH, -L 2A -OH, —O-L 2A -OH, —NH-L 2A -OH,

—OR 2A1 , -L 2A -OR 2A1 , —O-L 2A -OR 2A1 , —NH-L 2A -OR 2A1 ,

—NH 2 , —NHR 2A1 , —NR 2A1 2 , —NR 2A2 R 2A3

-L 2A -NH 2 , -L 2A -NHR 2A1 , -L 2A -NR 2A1 2 , -L 2A -NR 2A2 R 2A3 ,

—O-L 2A -NH 2 , —O-L 2A -NHR 2A1 , —O-L 2A -NR 2A1 2 , —O-L 2A -NR 2A2 R 2A3 ,

—NH-L 2A -NH 2 , —NH-L 2A -NHR 2A1 , —NH-L 2A -NR 2A1 2 , and —NH-L 2A -NR 2A2 R 2A3 .

9. A compound according to claim 2 , wherein each -Q C is independently selected from:

—R 2A1 , —F, —Cl, —Br, —I, —CF 3 , —OCF 3 ,

—NH-L 2A -OH, —NH-L 2A -OR 2A1 ,

—NH-L 2A -NH 2 , —NH-L 2A -NHR 2A1 , —NH-L 2A -NR 2A1 2 , and —NH-L 2A -NR 2A2 R 2A3 .

10. A compound according to claim 3 , wherein each -Q C is independently selected from:

—R 2A1 , —F, —Cl, —Br, —I, —CF 3 , —OCF 3 ,

—NH-L 2A -OH, —NH-L 2A -OR 2A1 ,

—NH-L 2A -NH 2 , —NH-L 2A -NHR 2A1 , —NH-L 2A -NR 2A1 2 , and —NH-L 2A -NR 2A2 R 2A3 .

11. A compound according to claim 4 , wherein each -Q C is independently selected from:

—R 2A1 , —F, —Cl, —Br, —I, —CF 3 , —OCF 3 ,

—NH-L 2A -OH, —NH-L 2A -OR 2A1 ,

—NH-L 2A -NH 2 , —NH-L 2A -NHR 2A1 , —NH-L 2A -NR 2A2 , and —NH-L 2A -NR 2A2 R 2A3 .

12. A compound according to claim 5 , wherein each -Q C is independently selected from:

—R 2A1 , —F, —Cl, —Br, —I, —CF 3 , —OCF 3 ,

—NH-L 2A -OH, —NH-L 2A -OR 2A1 ,

—NH-L 2A -NH 2 , —NH-L 2A -NHR 2A1 , —NH-L 2A -NR 2A1 2 , and —NH-L 2A -NR 2A2 R 2A3 .

13. A compound according to claim 6 , wherein each -Q C is independently selected from:

—R 2A1 , —F, —Cl, —Br, —I, —CF 3 , —OCF 3 ,

—NH-L 2A -OH, —NH-L 2A -OR 2A1 ,

—NH-L 2A -NH 2 , —NH-L 2A -NHR 2A1 , —NH-L 2A -NR 2A1 2 , and —NH-L 2A -NR 2A2 R 2A3 .

14. A compound of the following formula, or a pharmaceutically acceptable salt thereof:

wherein:

—R C1 is -Q C ;

each of —R C2 , —R C3 , and —R C4 is —H;

—R A3 is —H;

—R A6 is —H;

—R B3 is —H;

—R B5 is -Q B5 ;

—R B6 is -Q B6 ;

-Q B5 is —CN;

-Q B6 is —O—R QB6 ;

and wherein —R QB6 is independently selected from groups of the following formulae:

wherein:

p1 is independently 1, 2, 3, or 4;

p2 is independently 1, 2, 3, or 4;

p3 is independently 0, 1, or 2;

p4 is independently 1, 2, 3, or 4;

either: each —R NN1 is independently —H, saturated aliphatic C 1-4 alkyl, phenyl, or benzyl;

or: the group —NR NN1 R NN1 is independently azetidino, pyrrolidino, imidazolidino, pyrazolidino, piperidino, piperazino, morpholino, azepino, or diazepino, and is optionally substituted with one or more groups selected from C 1-3 alkyl, —CF 3 , and —F;

each —R NN2 is independently —H or saturated aliphatic C 1-4 alkyl;

each —R NN3 is independently —H, saturated aliphatic C 1-4 alkyl, phenyl, or benzyl; and

—R NN4 is -saturated aliphatic C 1-6 alkyl;

and wherein -Q C is independently selected from:

—R 2A1 , —F, —Cl, —Br, —I, —CF 3 , —OCF 3 ,

—OH, -L 2A -OH, —O-L 2A -OH, —NH-L 2A -OH,

—OR 2A1 , L 2A -OR 2A1 , —O-L 2A -OR 2A1 , —NH-L 2A -OR 2A1 ,

—NH 2 , —NHR 2A1 ; —NR 2A1 2 , —NR 2A2 R 2A3 ,

-L 2A NH 2 , -L 2A -NHR 2A1 , -L 2A -NR 2A1 2 ; -L 2A -NR 2A2 R 2A3 ,

—O-L 2A -NH 2 , —O-L 2A -NHR 2A1 , —O-L 2A -NR 2A1 2 , —O-L-NR 2A2 R 2A3 ,

—NH-L 2A -NH 2 , —NH-L 2A -NHR 2A1 , —NH-L 2A -NR 2A1 2 , —NH-L 2A -NR 2A2 R 2A3 ,

—C(═O)NH 2 , —C(═O)NHR 2A1 , —C(═O)NR 2A1 2 , —C(═O)NR 2A2 R 2A3 ,

—C(═O)NH-L 2A -OH, —C(═O)NH-L 2A -OR 2A1 ,

—C(═O)NH-L 2A -NH 2 , —C(═O)NH-L 2A -NHR 2A1 ,

—C(═O)NH-L 2A -C(═O)NH-L 2A - NR 2A2 R 2A3 ,

—NHC(═O)R 2A1 , —NR 2A1 C(═O)R 2A1 ,

—NHC(═O)-L 2A -OH, —NHC(═O)-L 2A -OR 2A1 ,

—NHC(═O)-L 2A -NH 2 , —NHC(═O)-L 2A -NHR 2A1 ,

—NHC(═O)-L 2A -NR 2A1 2 , and —NHC(═O)-L 2A -NR 2A2 R 2A3 ;

wherein:

each -L 2A - is saturated aliphatic C 1-5 alkylene;

each —NR 2A2 R 2A3 is independently pyrrolidino, piperidino, piperazino, or morpholino, and is optionally substituted with one or more groups selected from C 1-3 alkyl, —CF 3 , and —F;

each —R 2A1 is independently —R 2B1 , —R 2B7 , or -L 2B -R 2B7 ;

each —R 2B1 is saturated aliphatic C 1-6 alkyl;

each —R 2B7 is phenyl;

each -L 2B - is saturated aliphatic C 1-3 alkylene;

wherein:

each —R 2B7 is optionally substituted with one or more substituents —R 2C1 and/or one or more substituents —R 2C2 ;

each —R 2B1 and -L 2B - is optionally substituted with one or more substituents —R 2C2 ;

wherein:

each —R 2C1 is independently saturated aliphatic C 1-4 alkyl, phenyl, or benzyl;

each —R 2c2 is independently:

—F, —Cl, —Br, —I,

—CF 3 , —OCF 3 ,

—OH, -L 2D -OH, —O-L 2D -OH,

—OR 2D1 , L 2D -OR 2D1 , —O-L 2D -OR 2D1 ,

—SH, —SR 2D1 ,

—CN,

—NO 2 ,

—NH 2 , —NHR 2D1 , —NR 2D1 2 , —NR 2D2 R 2D3 ,

-L 2D -NH 2 , -L 2D -NHR 2D1 , -L 2D -NR 2D1 2 , -L 2D -NR 2D2 R 2D3 ,

—C(═O)OH, —C(═O)OR 2D1 ,

—C(═O)NH 2 , —C(═O)NHR 2D1 , —C(═O)NR 2D1 2 , or —C(═O)NR 2D2 R 2D3 ;

wherein:

each —R 2D1 is independently saturated aliphatic C 1-4 alkyl, phenyl, or benzyl;

each -L 2D - is saturated aliphatic C 1-5 alkylene; and

each —NR 2D2 R 2D3 is independently pyrrolidino, piperidino, piperazino, or morpholino, and is optionally substituted with one or more groups selected from C 1-3 alkyl, —CF 3 , and —F.

15. A compound according to claim 14 , wherein:

—R QB6 is a group of formula (B6-1B);

p1 is 1; and

each —R NN1 is independently —H or saturated aliphatic C 1-4 alkyl.

16. A compound of the following formula, or a pharmaceutically acceptable salt thereof:

wherein:

—R C1 is -Q C ;

each of —R C2 , —R C3 , and —R C4 is —H;

—R A3 is —H;

—R A6 is —H;

—R B3 is —H;

—R B5 is -Q B5 ;

—R B6 is -Q B6 ;

-Q B5 is —CN;

-Q B6 is —O—R QB6 ;

—R QB6 is:

p1 is 1;

each —R NN1 is independently —H or saturated aliphatic C 1-4 alkyl;

-Q C is independently —R X1 , —F, —Cl, —Br, —I, —CF 3 , —OCF 3 , —OH, —OR X1 , —NH 2 , —NHR X1 , —NR X1 2 , —R M1 , —NH—(CH 2 ) z —OH, —NH—(CH 2 ) z —OR X1 , —NH—(CH 2 ) z —NH 2 , —NH—(CH 2 ) z —NHR X1 , —NH—(CH 2 ) z —NR X1 2 , or —NH—(CH 2 ) z —R M1 ;

each z is independently 2 or 3;

each —R X1 is saturated aliphatic C 1-4 alkyl; and

each —R M1 is independently piperidino, piperizino, or morpholino, and is optionally substituted with one or more saturated aliphatic C 1-4 alkyl groups.

17. A compound according to claim 1 , which is a compound selected from the following compounds, or a pharmaceutically acceptable salt thereof:

18. A compound according to claim 16 , which is a compound selected from the following compounds, or a pharmaceutically acceptable salt thereof:

19. A pharmaceutical composition comprising a compound according to claim 1 , and a pharmaceutically acceptable carrier or diluent.