Granted Patent B2

US 10,208,011 · App. 15/893,295 · Granted Feb 19, 2019

Abstract

Claims (58)

1. A compound selected from:

or a pharmaceutically acceptable salt thereof;

wherein A is:

m is 0, 1, or 2;

n is 1, 2, or 3;

o is 0, 1, 2, 3, 4, or 5;

Z is selected from —O—, —C(R 3 ) 2 —, —CHR 3 —, —CH 2 —, —CHF—, —CF 2 —, and —S—;

Z A and Z B are independently selected from —O—, —C(R 3 ) 2 —, —CHR 3 —, —CH 2 —, —CHF—, —CF 2 —, and —S—;

each R 1 is independently selected from C 1 -C 3 alkyl, halogen, and C 1 -C 3 haloalkyl;

R 2 is selected from:

a. 4-6 membered heterocycle optionally substituted with one, two, or three groups independently selected from R 4 ;

b. —NH 2 , —NH(C 1 -C 3 alkyl or C 2 -C 3 haloalkyl), and —N((independently)C 1 -C 3 alkyl or C 2 -C 3 haloalkyl) 2 ;

c. monocyclic 7-8 membered heterocycle optionally substituted with one, two, or three groups independently selected from R 4 ; and

d. 6-12 membered bicyclic or bridged heterocycle optionally substituted with one, two, or three groups independently selected from R 4 ;

R 3 is independently selected from —F, —Cl, —Br, —CH 3 , —CH 2 F, —CHF 2 , and —CF 3 ;

R 4 is selected from hydrogen, halogen, C 1 -C 3 alkyl, and C 1 -C 3 haloalkyl; and

R 5 is selected from hydrogen, halogen, C 1 -C 3 alkyl, and C 1 -C 3 haloalkyl.

2. The compound of claim 1 , of Formula:

or a pharmaceutically acceptable salt thereof.

3. The compound of claim 1 , of Formula:

or a pharmaceutically acceptable salt thereof.

4. The compound of claim 1 , wherein Z is —O—.

5. The compound of claim 1 , wherein o is 3.

6. The compound of claim 1 selected from Formula:

or a pharmaceutically acceptable salt thereof.

7. The compound of claim 1 , wherein at least one R 1 is fluoro.

8. The compound of claim 1 , wherein at least one R 1 is methyl.

9. The compound of claim 1 , wherein R 2 is —N(CH 2 CH 3 ) 2 .

10. The compound of claim 1 , wherein R 2 is selected from

11. A compound selected from:

or a pharmaceutically acceptable salt thereof,

wherein A is:

Y is

m is 0, 1, or 2;

n is 1, 2, or 3;

o is independently 0, 1, 2, 3, 4, or 5;

Z is selected from —O—, —C(R 3 ) 2 —, —CHR 3 —, —CH 2 —, —CHF—, —CF 2 —, and —S—;

Z A and Z B are independently selected from —O—, —C(R 3 ) 2 —, —CHR 3 —, —CH 2 —, —CHF—, —CF 2 —, and —S—;

each R 1 is independently selected from C 1 -C 3 alkyl, halogen, and C 1 -C 3 haloalkyl;

R 2 is selected from:

a. 4-6 membered heterocycle optionally substituted with one, two, or three groups independently selected from R 4 ;

b. —NH 2 , —NH(C 1 -C 3 alkyl or C 2 -C 3 haloalkyl), and —N((independently)C 1 -C 3 alkyl or C 2 -C 3 haloalkyl) 2 ;

c. monocyclic 7-8 membered heterocycle optionally substituted with one, two, or three groups independently selected from R 4 ;

d. 6-12 membered bicyclic or bridged heterocycle optionally substituted with one, two, or three groups independently selected from R 4 ; and

e. hydroxyl, alkoxy, —NH—(CH 2 ) n1 —NH 2 , —NH—(CH 2 ) n1 —NH(C 1 -C 12 alkyl or C 2 -C 12 haloalkyl), —NH—(CH 2 ) n1 —N((independently)C 1 -C 12 alkyl or C 2 -C 12 haloalkyl), —NHC 4 -C 12 alkyl, and —N(C 1 -C 12 alkyl) 2 ;

n1 is 2, 3, 4, 5, or 6;

R 3 is independently selected from —F, —Cl, —Br, —CH 3 , —CH 2 F, —CHF 2 , and —CF 3 ;

R 4 is selected from hydrogen, halogen, C 1 -C 3 alkyl, and C 1 -C 3 haloalkyl;

or R 4 is selected from hydrogen, halogen, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, —COOH, —COOC 1 -C 12 alkyl, —CONH 2 , —CON(H)alkyl, and —CON(alkyl) 2 ;

R 5 is selected from hydrogen, halogen, C 1 -C 3 alkyl, and C 1 -C 3 haloalkyl; and

R 7 is a 4, 5, 6, 7, 8, 9, or 10 membered heterocycle optionally substituted with 1, 2, or 3 groups selected from R 4 .

12. The compound of claim 11 selected from

or a pharmaceutically acceptable salt thereof.

13. The compound of claim 11 selected from

or a pharmaceutically acceptable salt thereof.

14. The compound of claim 11 selected from:

or a pharmaceutically acceptable salt thereof.

15. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

Assignments (8)