IP Library › Granted Patent US 12,384,775
Granted Patent B2
US 12,384,775 · App. 18/187,789 · Granted Aug 12, 2025

Pyrimid-2-yl-pyrazole compounds as IRAK inhibitors

Inventors: Jack Maung (South San Francisco, CA); Yan Chen (South San Francisco, CA); Simon Shaw (South San Francisco, CA); David Sweeny (South San Francisco, CA); Esteban Masuda (South San Francisco, CA)
Assignee: Rigel Pharmaceuticals, Inc.
C07D417/14
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Quick Facts
Patent No.
US 12,384,775
App. No.
18/187,789
Granted
Aug 12, 2025
Kind
B2
Abstract

Disclosed embodiments concern novel interleukin receptor associated kinases (IRAK) inhibitor compounds and compositions comprising such compounds. The compounds may have a structure according to Formula I Also disclosed are methods of making and using the compounds and compositions. The disclosed compounds and/or compositions may be used to treat or prevent an IRAK-associated disease or condition.

Claims (39)

1. A compound having a structure according to Formula I

or a pharmaceutically acceptable salt or solvate thereof, wherein:

R 1 is H, aliphatic, or alkyl phosphate;

R 2 is C 1-6 alkyl.

2. The compound of claim 1 , wherein R 1 is H, alkyl, or -alkylOP(O)(OR) 2 , where each OR is —OH, —Oalkyl, —Oaryl, —Oheteroaryl, —Oaralkyl, or —OM + where M + is a counter ion with a single positive charge.

3. The compound of claim 2 , wherein R 1 is —CH(CH 3 )OP(O)(OR) 2 or —CH 2 OP(O)(OR) 2 .

4. The compound of claim 1 , wherein R 2 is C 1-4 alkyl.

5. The compound of claim 1 , wherein the compound has a structure according to Formula II

or a pharmaceutically acceptable salt or solvate thereof.

6. The compound of claim 5 , wherein R 1 is wherein R 1 is H or C 1-4 alkyl phosphate.

7. The compound of claim 5 , wherein R 1 is —CH 2 OP(O)(OH) 2 , —CH(CH 3 )OP(O)(OH) 2 , or a pharmaceutically acceptable salt thereof.

8. The compound of claim 1 , wherein R 1 is H, or C 1-4 alkyl phosphate.

9. The compound of claim 2 , wherein R 1 is —CH 2 OP(O)(OR) 2 .

10. The compound of claim 9 , wherein:

R 1 is —CH 2 OP(O)(OH) 2 ;

R 1 is —CH 2 OP(O) (OC 1-6 alkyl) 2 ; or

R 1 is —CH 2 OP(O) (O − M + ) 2 .

11. The compound of claim 10 , wherein R 1 is —CH 2 OP(O)(O − Na + ) 2 .

12. The compound of claim 1 , wherein the compound is a salt co-crystal.

13. The compound of claim 1 , wherein the compound is in a free base form.

14. The compound of claim 12 , wherein the salt co-crystal is a tartaric acid salt co-crystal or a tris salt co-crystal.

15. The compound of claim 1 , selected from:

I-1: N-(1-((1r,4r)-4-ethoxycyclohexyl)-3-(pyrimidin-2-yl)-1H-pyrazol-4-yl)-2-(1H-pyrazol-4-yl) thiazole-4-carboxamide;

I-2: (4-(4-((1-((1r,4r)-4-ethoxycyclohexyl)-3-(pyrimidin-2-yl)-1H-pyrazol-4-yl) carbamoyl) thiazol-2-yl)-1H-pyrazol-1-yl)methyl dihydrogen phosphate;

I-3: sodium (4-(4-((1-((1r,4r)-4-ethoxycyclohexyl)-3-(pyrimidin-2-yl)-1H-pyrazol-4-yl) carbamoyl) thiazol-2-yl)-1H-pyrazol-1-yl)methyl phosphate;

I-4: N-(1-((1r,4r)-4-ethoxycyclohexyl)-3-(pyrimidin-2-yl)-1H-pyrazol-4-yl)-2-(1H-pyrazol-4-yl) thiazole-4-carboxamide tartaric acid salt;

I-5: (4-(4-((1-((1r,4r)-4-ethoxycyclohexyl)-3-(pyrimidin-2-yl)-1H-pyrazol-4-yl) carbamoyl) thiazol-2-yl)-1H-pyrazol-1-yl)methyl hydrogen phosphate 1,3-dihydroxy-2-(hydroxymethyl) propan-2-aminium (tris salt);

I-6:1-(4-(4-((1-((1r,4r)-4-ethoxycyclohexyl)-3-(pyrimidin-2-yl)-1H-pyrazol-4-yl) carbamoyl) thiazol-2-yl)-1H-pyrazol-1-yl)ethyl dihydrogen phosphate;

I-7: sodium 1-(4-(4-((1-((1r,4r)-4-ethoxycyclohexyl)-3-(pyrimidin-2-yl)-1H-pyrazol-4-yl) carbamoyl) thiazol-2-yl)-1H-pyrazol-1-yl)ethyl phosphate; and

I-8:1-(4-(4-((1-((1r,4r)-4-ethoxycyclohexyl)-3-(pyrimidin-2-yl)-1H-pyrazol-4-yl) carbamoyl) thiazol-2-yl)-1H-pyrazol-1-yl)ethyl hydrogen phosphate 1,3-dihydroxy-2-(hydroxymethyl) propan-2-aminium (tris salt).

16. The compound of claim 15 , wherein the compound is I-1: N-(1-((1r,4r)-4-ethoxycyclohexyl)-3-(pyrimidin-2-yl)-1H-pyrazol-4-yl)-2-(1H-pyrazol-4-yl) thiazole-4-carboxamide.

17. The compound of claim 15 , wherein the compound is I-2: (4-(4-((1-((1r,4r)-4-ethoxycyclohexyl)-3-(pyrimidin-2-yl)-1H-pyrazol-4-yl) carbamoyl) thiazol-2-yl)-1H-pyrazol-1-yl)methyl dihydrogen phosphate.

18. The compound of claim 15 , wherein the compound is I-3: sodium (4-(4-((1-((1r,4r)-4-ethoxycyclohexyl)-3-(pyrimidin-2-yl)-1H-pyrazol-4-yl) carbamoyl) thiazol-2-yl)-1H-pyrazol-1-yl)methyl phosphate.

19. A compound that is I-1: N-(1-((1r,4r)-4-ethoxycyclohexyl)-3-(pyrimidin-2-yl)-1H-pyrazol-4-yl)-2-(1H-pyrazol-4-yl) thiazole-4-carboxamide or a pharmaceutically acceptable salt or solvate thereof.

20. A pharmaceutical composition comprising a compound according to claim 1 , and a pharmaceutically acceptable excipient.

21. A pharmaceutical composition, comprising:

a means for delivering an IRAK inhibitory moiety, wherein the IRAK inhibitory moiety comprises the compound of claim 1 ; and

a pharmaceutically acceptable excipient.

22. The pharmaceutical composition of claim 21 , wherein the means for delivering an IRAK inhibitory moiety comprises a means for inhibiting an IRAK protein in vivo.

Assignments (2)
SECURITY INTEREST Recorded May 8, 2026
From: RIGEL PHARMACEUTICALS, INC.
To: MIDCAP FUNDING IV TRUST
Reel/Frame 075576/0880 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 9, 2026
From: MAUNG, JACK; CHEN, YAN; SHAW, SIMON; SWEENY, DAVID; MASUDA, ESTEBAN
To: RIGEL PHARMACEUTICALS, INC.
Reel/Frame 073417/0923 →
Continuity (2)
Provisional Application 63322955 · Mar 23, 2022
Related Publication 20230303555A1 · Sep 28, 2023
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