Cyclopentane-based modulators of STING (stimulator of interferon genes)

Patent metadata

Field	Value
Publication number	US-10538542-B2
Application number	US-201916297910-A
Country	US
Kind code	B2
Filing date	Mar 11, 2019
Priority date	Mar 15, 2018
Publication date	Jan 21, 2020
Grant date	Jan 21, 2020

Abstract

Compounds of the general formula (I):

or a pharmaceutically acceptable salt thereof, processes for the preparation of these compounds, compositions containing these compounds, and the uses of these compounds.

First claim

We claim:

1. A compound of formula (I):

or a pharmaceutically acceptable salt thereof, wherein
each J is independently oxygen (O) or sulfur (S);
R 1 is selected from:

R 2 is selected from:

W is OH, SH, O − M + or S − M + , where M + represents a cationic counter-ion;
X is OH, SH, O − M + or S − M + , where M + represents a cationic counter-ion;
each Y is independently selected from hydrogen, halogen, C 1 -C 6 alkyl, substituted C 1 -C 6 alkyl, N(R 3 ) 2 , and OR 4 , or the two Y substituents join to form a 3-5 membered spirocyclic ring system comprising 0-1 heteroatoms;
each Z is independently selected from hydrogen, halogen, C 1 -C 6 alkyl, substituted C 1 -C 6 alkyl, N(R 3 ) 2 , and OR 4 , or the two Z substituents join to form a 3-5 membered spirocyclic ring system comprising 0-1 heteroatoms; and
R 3 and R 4 are each independently hydrogen or C 1 -C 6 alkyl.

2. A compound of formula (II):

or a pharmaceutically acceptable salt thereof, wherein
R 1 is selected from:

R 2 is selected from:

W is OH, SH, O − M + or S − M + , where M + represents a cationic counter-ion;
X is OH, SH, O − M + or S − M + , where M + represents a cationic counter-ion;
each Y is independently selected from hydrogen, halogen, C 1 -C 6 alkyl, substituted C 1 -C 6 alkyl, N(R 3 ) 2 , and OR 4 , or the two Y substituents join to form a 3-5 membered spirocyclic ring system comprising 0-1 heteroatoms;
each Z is independently selected from hydrogen, halogen, C 1 -C 6 alkyl, substituted C 1 -C 6 alkyl, N(R 3 ) 2 , and OR 4 , or the two Z substituents join to form a 3-5 membered spirocyclic ring system comprising 0-1 heteroatoms; and
R 3 and R 4 are each independently hydrogen or C 1 -C 6 alkyl.

3. The compound or salt of claim 1 , wherein M + is selected from the group consisting of sodium, potassium, calcium, ammonium, triethylammonium, trimethylammonium and magnesium.

4. The compound or salt of claim 1 , wherein each counter-ion M + is the same.

5. The compound or salt of claim 1 , wherein R 1 is

and R 2 is

6. The compound or salt of claim 1 , wherein R 1 is

and R 2 is

7. The compound or salt of claim 1 , wherein R 1 is

and R 2 is

8. The compound or salt of claim 1 , wherein R 1 is

and R 2 is

9. The compound or salt of claim 1 , wherein R 1 is

and R 2 is

10. The compound or salt of claim 1 , wherein R 1 is

and R 2 is

11. The compound or salt of claim 1 , wherein R 1 is

and R 2 is

12. The compound or salt of claim 1 , wherein R 1 is

and R 2 is

13. The compound or salt of claim 1 , wherein R 1 is

and R 2 is

14. The compound or salt of claim 1 , wherein R 1 is

and R 2 is

15. The compound or salt of claim 1 , wherein R 1 is

and R 2 is

16. The compound or salt of claim 1 , wherein R 1 is

and R 2 is

17. The compound or salt of claim 1 , wherein R 1 is

and R 2 is

18. The compound or salt of claim 1 , wherein one or both Y is halogen.

19. The compound or salt of claim 1 , wherein one Y is hydrogen and the other Y is a halogen.

20. The compound or salt of claim 19 , wherein said halogen is fluorine.

21. The compound or salt of claim 1 , wherein one Z is hydrogen and the other Z is OR 4 .

22. The compound or salt of claim 1 , wherein W is —SH and X is —SH.

23. The compound or salt of claim 1 , wherein W is —OH and X is —OH.

24. The compound or salt of claim 1 , wherein W is —SH and X is —OH.

25. The compound or salt of claim 1 , wherein W is —OH and X is —SH.

26. A compound selected from:

Assignees

• Pfizer

Inventors

• Wythes Martin James
• Mcalpine Indrawan James
• Patman Ryan
• Rui Eugene Yuanjin
• Fensome Andrew
• Maderna Andreas
• Jalaie Mehran
• Gajiwala Ketan S

Classifications

• C07H19/213 Primary

  containing cyclic phosphate · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07F9/65744 Primary

  condensed with carbocyclic or heterocyclic rings or ring systems · CPC title

• A61K47/6801

  Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent · CPC title

• C07H19/23 Primary

  Heterocyclic radicals containing two or more heterocyclic rings condensed among themselves or condensed with a common carbocyclic ring system, not provided for in groups C07H19/14 - C07H19/22 · CPC title