IP Library › Granted Patent US 11,339,159
Granted Patent B2
US 11,339,159 · App. 16/926,933 · Granted May 24, 2022

Toll-like receptor agonists

Inventors: Omar Ahmad (Cambridge, MA); Andrew Fensome (Harvard, MA); Erik Alphie LaChapelle (Uncasville, CT); Ethan Lawrence Fisher (Chester, CT); Rayomand J. Unwalla (Bedford, MA); Jun Xiao (East Lyme, CT); Lei Zhang (Auburndale, MA)
Assignee: Pfizer Inc.
C07D471/04A61K31/437
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Quick Facts
Patent No.
US 11,339,159
App. No.
16/926,933
Granted
May 24, 2022
Kind
B2
Abstract

The present invention relates to imidazo-pyridinyl compounds, or a pharmaceutically acceptable salt thereof, to pharmaceutical compositions comprising such compounds and salts, and to methods of using such compounds, salts and compositions for the treatment of abnormal cell growth, including cancer, in a subject.

Claims (93)

1. A compound of Formula (I)

or a pharmaceutically acceptable salt thereof, wherein

R 1 and R 2 are independently C 1-3 alkyl; or

R 1 and R 2 are joined to form a 5- to 7-membered carbocyclic ring, wherein said carbocyclic ring may be saturated or unsaturated;

R 3 is

R 4 is C 1-6 alkyl, or (CH 2 ) n O(CH 2 ) m CH 3 , wherein the C 1-6 alkyl or any carbon of the (CH 2 ) n O(CH 2 ) m CH 3 group is substituted with 0 to 3 halogen as valency allows;

R 5 is C 1-3 alkyl, or OC 1-3 alkyl, wherein the C 1-3 alkyl is substituted by 0 to 3 F;

R 6 is H, or C 1-3 alkyl, wherein the C 1-3 alkyl is substituted with 0 to 3 F;

m is 0 to 2; and

n is 1 to 3.

2. A compound of Formula (Ia)

or a pharmaceutically acceptable salt thereof, wherein

R 1 and R 2 are independently C 1-2 alkyl; or

R 1 and R 2 are joined to form a 5- to 7-membered carbocyclic ring, wherein said carbocyclic ring may be saturated or unsaturated;

R 3 is

R 4 is C 3-5 alkyl, or (CH 2 ) n O(CH 2 ) m CH 3 ;

R 5 is C 1-2 alkyl;

R 6 is H;

m is 1; and

n is 1.

3. The compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein R 1 and R 2 are independently C 1-2 alkyl.

4. The compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein R 1 and R 2 are joined to form a 5- to 7-membered carbocyclic ring, wherein said carbocyclic ring may be saturated or unsaturated.

5. The compound of claim 4 , or a pharmaceutically acceptable salt thereof, wherein R 1 and R 2 are joined to form a 5- to 7-membered carbocyclic ring, wherein said carbocyclic ring may be saturated.

6. The compound of claim 5 , or a pharmaceutically acceptable salt thereof, wherein the carbocyclic ring is cyclopentyl.

7. The compound of claim 5 , or a pharmaceutically acceptable salt thereof, wherein the carbocyclic ring is cyclohexyl.

8. The compound of claim 4 , or a pharmaceutically acceptable salt thereof, wherein

R 1 and R 2 are joined to form a 5- to 7-membered carbocyclic ring, wherein said carbocyclic ring may be unsaturated; and

R 4 is C 3-5 alkyl.

9. The compound of claim 8 , or a pharmaceutically acceptable salt thereof, wherein the carbocyclic ring is phenyl.

10. A compound of Formula (Ib)

or a pharmaceutically acceptable salt thereof, wherein

R 1 and R 2 are independently C 1-3 alkyl; or

R 1 and R 2 are joined to form a 5- to 7-membered carbocyclic ring, wherein said carbocyclic ring may be saturated or unsaturated;

R 3 is

R 4 is C 1-6 alkyl, or (CH 2 ) n O(CH 2 ) m CH 3 , wherein said C 1-6 alkyl or any carbon of the (CH 2 ) n O(CH 2 ) m CH 3 group is substituted with 0 to 3 halogen as valency allows, wherein halogen is F;

R 5 is C 1-3 alkyl, or OC 1-3 alkyl, wherein the C 1-3 alkyl is substituted by 0 to 3 F;

R 6 is H, or C 1-3 alkyl, wherein the C 1-3 alkyl is substituted with 0 to 3 F;

m is 0 to 2; and

n is 1 to 3.

11. The compound of claim 10 , or a pharmaceutically acceptable salt thereof, wherein

R 1 and R 2 are independently C 1-2 alkyl; or

R 1 and R 2 are joined to form a 5- to 7-membered carbocyclic ring, wherein said carbocyclic ring may be saturated or unsaturated;

R 3 is

R 5 is C 1-3 alkyl, or OC 1-3 alkyl, wherein the C 1-3 alkyl is substituted by 0 to 2 F; and

R 6 is H.

12. The compound of claim 11 , or a pharmaceutically acceptable salt thereof, wherein R 5 is C 1-2 alkyl.

13. A compound selected from:

2-((4-amino-2-(ethoxymethyl)-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-1-yl)methyl)-2-methylpropane-1,3-diol;

2-((4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl)methyl)-2-methylpropane-1,3-diol;

2-((4-amino-2-(ethoxymethyl)-7,8-dihydrocyclopenta[b]imidazo[4,5-d]pyridin-1(6H)-yl)methyl)-2-methylpropane-1,3-diol;

2-((4-amino-2-(ethoxymethyl)-6,7,8,9-tetrahydro-1H-imidazo[4,5-c]quinolin-1-yl)methyl)-2-methylpropane-1,3-diol;

3-(4-amino-2-(ethoxymethyl)-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-1-yl)-2-(methoxymethyl)-2-methylpropan-1-ol;

(R)-3-(4-amino-2-(ethoxymethyl)-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-1-yl)-2-(methoxymethyl)-2-methylpropan-1-ol;

(S)-3-(4-amino-2-(ethoxymethyl)-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-1-yl)-2-(methoxymethyl)-2-methylpropan-1-ol;

2-((4-amino-6,7-dimethyl-2-(2,2,2-trifluoroethyl)-1H-imidazo[4,5-c]pyridin-1-yl)methyl)-2-methylpropane-1,3-diol;

2-((4-amino-2-(ethoxymethyl)-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-1-yl)methyl)-2-ethylpropane-1,3-diol;

2-((4-amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)methyl)-2-methylpropane-1,3-diol;

2-((4-amino-2-butyl-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-1-yl)methyl)-2-methylpropane-1,3-diol; and

2-((4-amino-2-pentyl-1H-imidazo[4,5-c]quinolin-1-yl)methyl)-2-methylpropane-1,3-diol;

or a pharmaceutically acceptable salt thereof.

14. A compound that is 2-((4-amino-2-(ethoxymethyl)-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-1-yl)methyl)-2-methylpropane-1,3-diol; or a pharmaceutically acceptable salt thereof.

15. The compound of claim 14 that is 2-((4-amino-2-(ethoxymethyl)-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-1-yl)methyl)-2-methylpropane-1,3-diol.

16. A compound that is 2-((4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl)methyl)-2-methylpropane-1,3-diol; or a pharmaceutically acceptable salt thereof.

17. The compound of claim 16 that is 2-((4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl)methyl)-2-methylpropane-1,3-diol.

18. A compound that is 2-((4-amino-2-(ethoxymethyl)-7,8-dihydrocyclopenta[b]imidazo[4,5-d]pyridin-1(6H)-yl)methyl)-2-methylpropane-1,3-diol; or

2-((4-amino-2-(ethoxymethyl)-6,7,8,9-tetrahydro-1H-imidazo[4,5-c]quinolin-1-yl)methyl)-2-methylpropane-1,3-diol;

or a pharmaceutically acceptable salt thereof.

19. The compound of claim 18 that is 2-((4-amino-2-(ethoxymethyl)-7,8-dihydrocyclopenta[b]imidazo[4,5-d]pyridin-1(6H)-yl)methyl)-2-methylpropane-1,3-diol; or

2-((4-amino-2-(ethoxymethyl)-6,7,8,9-tetrahydro-1H-imidazo[4,5-c]quinolin-1-yl)methyl)-2-methylpropane-1,3-diol.

20. A compound that is 3-(4-amino-2-(ethoxymethyl)-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-1-yl)-2-(methoxymethyl)-2-methylpropan-1-01;

(R)-3-(4-amino-2-(ethoxymethyl)-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-1-yl)-2-(methoxymethyl)-2-methylpropan-1-ol; or

(S)-3-(4-amino-2-(ethoxymethyl)-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-1-yl)-2-(methoxymethyl)-2-methylpropan-1-ol;

or a pharmaceutically acceptable salt thereof.

21. The compound of claim 20 that is 3-(4-amino-2-(ethoxymethyl)-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-1-yl)-2-(methoxymethyl)-2-methylpropan-1-ol;

(R)-3-(4-amino-2-(ethoxymethyl)-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-1-yl)-2-(methoxymethyl)-2-methylpropan-1-ol; or

(S)-3-(4-amino-2-(ethoxymethyl)-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-1-yl)-2-(methoxymethyl)-2-methylpropan-1-ol.

22. A compound that is 2-((4-amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)methyl)-2-methylpropane-1,3-diol; or

2-((4-amino-2-pentyl-1H-imidazo[4,5-c]quinolin-1-yl)methyl)-2-methylpropane-1,3-diol;

or a pharmaceutically acceptable salt thereof.

23. The compound of claim 22 that is 2-((4-amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)methyl)-2-methylpropane-1,3-diol; or

2-((4-amino-2-pentyl-1H-imidazo[4,5-c]quinolin-1-yl)methyl)-2-methylpropane-1,3-diol.

24. A pharmaceutical composition comprising the compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.

25. A compound selected from

2-((4-amino-2-butyl-6,7,8,9-tetrahydro-1H-imidazo[4,5-c]quinolin-1-yl)methyl)-2-methylpropane-1,3-diol;

2-((4-amino-2-butyl-7,8-dihydrocyclopenta[b]imidazo[4,5-d]pyridin-1(6H)-yl)methyl)-2-methylpropane-1,3-diol;

2-((4-amino-2-ethyl-1H-imidazo[4,5-c]quinolin-1-yl)methyl)-2-methylpropane-1,3-diol; and

2-((4-amino-2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)methyl)-2-methylpropane-1,3-diol;

or a pharmaceutically acceptable salt thereof.

26. A compound of claim 25 , or a pharmaceutically acceptable salt thereof, that is 2-((4-amino-2-butyl-6,7,8,9-tetrahydro-1H-imidazo[4,5-c]quinolin-1-yl)methyl)-2-methylpropane-1,3-diol.

27. A compound of claim 25 , or a pharmaceutically acceptable salt thereof, that is 2-((4-amino-2-butyl-7,8-dihydrocyclopenta[b]imidazo[4,5-d]pyridin-1(6H)-yl)methyl)-2-methylpropane-1,3-diol.

28. A compound of claim 25 , or a pharmaceutically acceptable salt thereof, that is 2-((4-amino-2-ethyl-1H-imidazo[4,5-c]quinolin-1-yl)methyl)-2-methylpropane-1,3-diol.

29. A compound of claim 25 , or a pharmaceutically acceptable salt thereof, that is 2-((4-amino-2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)methyl)-2-methylpropane-1,3-diol.

30. A pharmaceutical composition comprising the compound of claim 25 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.

Assignments (1)
ASSIGNEE ADDRESS CORRECTION Recorded Mar 20, 2023
From: PFIZER INC.
To: PFIZER INC.
Reel/Frame 063119/0087 →