IP Library › Granted Patent US 10,919,854

Granted Patent B2

US 10,919,854 · App. 15/930,738 · Granted Feb 16, 2021

Mono- or di-substituted indole derivatives as dengue viral replication inhibitors

Inventors: Bart Rudolf Romanie Kesteleyn (Beerse, BE); Jean-François Bonfanti (Issy-les-Moulineaux, FR); Tim Hugo Maria Jonckers (Beerse, BE); Pierre Jean-Marie Bernard Raboisson (Beerse, BE); Dorothée Alice Marie-Eve Bardiot (Leuven, BE); Arnaud Didier M Marchand (Leuven, BE)

Assignees: Janssen Pharmaceuticals, Inc.; Katholieke Universiteit Leuven

C07D209/14 A61K31/404 A61K45/06 A61P31/14 C07D209/04 C07D471/08 C07D487/08 C07D513/08

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Quick Facts

Patent No.: US 10,919,854
App. No.: 15/930,738
Granted: Feb 16, 2021
Kind: B2

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Abstract

The present invention relates to mono- or di-substituted indole compounds, methods to prevent or treat dengue viral infections by using the compounds and also relates to use of the compounds as a medicine, more preferably for use as a medicine to treat or prevent dengue viral infections. The present invention furthermore relates to pharmaceutical compositions or combination preparations of the compounds, to the compositions or preparations for use as a medicine, more preferably for the prevention or treatment of dengue viral infections. The invention also relates to processes for preparation of the compounds.

Claims (158)

1. A compound of formula (I)

wherein R 1 , R 2 and R 3 are selected from the group consisting of:

R 1 is H, R 2 is F and R 3 is H or CH 3 ,

R 1 is H, CH 3 or F, R 2 is OCH 3 and R 3 is H,

R 1 is H, R 2 is OCH 3 and R 3 is CH 3 ,

R 1 is CH 3 , R 2 is F and R 3 is H,

R 1 is CF 3 , R 2 is H and R 3 is H,

R 1 is OCF 3 , R 2 is OCH 3 and R 3 is H, and

R 1 is OCF 3 , R 2 is H and R 3 is CH 3 ,

or a stereoisomer, pharmaceutically acceptable salt, solvate or polymorph thereof.

2. A compound of claim 1 selected from the group consisting of:

or a stereoisomer, pharmaceutically acceptable salt, solvate or polymorph thereof.

3. A pharmaceutical composition comprising the compound of claim 1 and one or more pharmaceutically acceptable excipients, diluents or carriers.

4. A compound or a stereoisomer, pharmaceutically acceptable salt, solvate or polymorph thereof, according to claim 1 , wherein said compound is in a crystalline form.

5. A compound or a stereoisomer, pharmaceutically acceptable salt, or solvate thereof, according to claim 1 , wherein said compound is in an amorphous form.

6. A compound or a stereoisomer, pharmaceutically acceptable salt, or polymorph thereof, according to claim 1 , wherein said compound is in an un-solvated form, or a pharmaceutically acceptable salt thereof.

7. A method of treating a Dengue viral infection in a patient in need thereof comprising administering to the patient a compound of claim 1 .

8. The method of claim 7 , further comprising administering another antiviral agent to the patient.

9. A compound according to claim 1 , wherein said compound is:

Enantiomer 1A,

wherein 1 H NMR (500 MHz, DMSO-d 6 ) δ ppm 3.09 (s, 3H) 3.72 (s, 3H) 4.00 (s, 3H) 6.24 (d, J=7.9 Hz, 1H) 6.59 (s, 2H) 6.91 (s, 1H) 6.97 (dd, J=8.8, 2.2 Hz, 1H) 7.02-7.10 (m, 2H) 7.12 (d, J=2.2 Hz, 1H) 7.27 (dd, J=9.6, 2.2 Hz, 1H) 7.35 (d, J=8.2 Hz, 1H) 8.14 (dd, J=8.8, 5.7 Hz, 1H) 8.44 (s, 1H) 12.10 (br. s., 1H)

LC/MS (method LC-C): R t 3.09 min, MH + 517

[α] D 20 : +130.3° (c 0.277, DMF)

Chiral SFC (method SFC-D): R t 3.41 min, MH + 517, chiral purity 100%,

or a pharmaceutically acceptable salt, solvate or polymorph thereof.

10. A compound according to claim 1 , wherein said compound is:

Enantiomer 1n,

wherein 1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 3.09 (s, 3H) 3.72 (s, 3H) 4.00 (s, 3H) 6.24 (d, J=7.6 Hz, 1H) 6.53-6.65 (m, 2H) 6.91 (s, 1H) 6.97 (dd, J=8.6, 2.0 Hz, 1H) 7.01-7.09 (m, 2H) 7.12 (d, J=2.0 Hz, 1H) 7.27 (dd, J=9.6, 2.0 Hz, 1H) 7.35 (d, J=8.1 Hz, 1H) 8.14 (dd, J=8.6, 5.6 Hz, 1H) 8.43 (s, 1H) 12.09 (br. s., 1H)

LC/MS (method LC-C): R t 3.09 min, MH + 517

[α] D 20 : −135.3° (c 0.283, DMF)

Chiral SFC (method SFC-D): R t 4.89 min, MH + 517, chiral purity 99.35%,

or a pharmaceutically acceptable salt, solvate or polymorph thereof.

11. A compound according to claim 1 , wherein said compound is:

Enantiomer 2A,

wherein 1 H NMR (500 MHz, DMSO-d 6 ) δ ppm 2.37-2.39 (m, 3H) 3.09 (s, 3H) 3.72 (s, 3H) 4.01 (s, 3H) 6.26 (d, J=7.9 Hz, 1H) 6.54-6.63 (m, 2H) 6.92 (s, 1H) 6.97 (dd, J=8.4, 1.9 Hz, 1H) 7.02 (dd, J=9.9, 9.0 Hz, 1H) 7.07 (d, J=7.9 Hz, 1H) 7.13 (d, J=1.9 Hz, 1H) 7.35 (d, J=8.4 Hz, 1H) 7.96 (dd, J=8.5, 5.4 Hz, 1H) 8.45 (s, 1H) 12.24 (br. s., 1H)

LC/MS (method LC-C): R t 3.20 min, MH + 531

[α] D 20 : +104.5° (c 0.2545, DMF)

Chiral SFC (method SFC-A): R t 4.22 min, MH + 531, chiral purity 100%,

or a pharmaceutically acceptable salt, solvate or polymorph thereof.

12. A compound according to claim 1 , wherein said compound is:

Enantiomer 2B,

wherein 1 H NMR (500 MHz, DMSO-d 6 ) δ ppm 2.36-2.41 (m, 3H) 3.09 (s, 3H) 3.72 (s, 3H) 4.01 (s, 3H) 6.26 (d, J=7.9 Hz, 1H) 6.57-6.64 (m, 2H) 6.92 (s, 1H) 6.97 (dd, J=8.2, 1.9 Hz, 1H) 6.99-7.04 (m, 1H) 7.07 (d, J=7.9 Hz, 1H) 7.13 (d, J=1.9 Hz, 1H) 7.35 (d, J=8.2 Hz, 1H) 7.96 (dd, J=8.7, 5.2 Hz, 1H) 8.45 (s, 1H) 12.24 (br. s., 1H)

LC/MS (method LC-C): R t 3.20 min, MH + 531

[α] D 20 : 104.1° (c 0.2536, DMF)

Chiral SFC (method SFC-A): R t 5.12 min, MH + 531, chiral purity 99.53%,

or a pharmaceutically acceptable salt, solvate or polymorph thereof.

13. A compound according to claim 1 , wherein said compound is:

Enantiomer 3A,

wherein 1 H NMR (360 MHz, DMSO-d 6 ) δ ppm 3.09 (s, 3H) 3.72 (s, 3H) 3.77 (s, 3H) 4.01 (s, 3H) 6.22 (d, J=8.1 Hz, 1H) 6.55-6.61 (m, 2H) 6.84 (dd, J=8.8, 2.2 Hz, 1H) 6.91 (t, J=1.8 Hz, 1H) 6.94-7.00 (m, 2H) 7.07 (d, J=7.0 Hz, 1H) 7.13 (d, J=1.8 Hz, 1H) 7.35 (d, J=8.4 Hz, 1H) 8.02 (d, J=8.8 Hz, 1H) 8.32 (d, J=2.9 Hz, 1H) 11.87 (d, J=2.6 Hz, 1H)

LC/MS (method LC-A): R t 1.08 min, MH + 529

[α] D 20 : +134.9° (c 0.545, DMF)

Chiral SFC (method SFC-E): R t 4.31 min, MH + 529, chiral purity 100%,

or a pharmaceutically acceptable salt, solvate or polymorph thereof.

14. A compound according to claim 1 , wherein said compound is:

Enantiomer 3B,

wherein 1 H NMR (360 MHz, DMSO-d 6 ) δ ppm 3.09 (s, 3H) 3.72 (s, 3H) 3.77 (s, 3H) 4.01 (s, 3H) 6.21 (d, J=8.1 Hz, 1H) 6.54-6.62 (m, 2H) 6.83 (dd, J=8.6, 2.4 Hz, 1H) 6.91 (t, J=1.5 Hz, 1H) 6.94-6.99 (m, 2H) 7.07 (d, J=7.0 Hz, 1H) 7.13 (d, J=1.8 Hz, 1H) 7.35 (d, J=8.1 Hz, 1H) 8.02 (d, J=8.8 Hz, 1H) 8.32 (d, J=2.9 Hz, 1H) 11.87 (br d, J=2.2 Hz, 1H)

LC/MS (method LC-A): R t 1.08 min, MH + 529

[α] D 20 : −167° (c 0.51, DMF)

Chiral SFC (method SFC-E): R t 4.63 min, MH + 529, chiral purity 94.7%,

or a pharmaceutically acceptable salt, solvate or polymorph thereof.

15. A compound according to claim 1 , wherein said compound is:

Enantiomer 4A,

wherein 1 H NMR (500 MHz, DMSO-d 6 ) δ ppm 2.21 (s, 3H) 3.09 (s, 3H) 3.72 (s, 3H) 3.79 (s, 3H) 4.01 (s, 3H) 6.20 (d, J=7.6 Hz, 1H) 6.58 (d, J=1.6 Hz, 2H) 6.87-6.93 (m, 2H) 6.96 (dd, J=8.2, 1.9 Hz, 1H) 7.02 (d, J=7.6 Hz, 1H) 7.12 (d, J=1.9 Hz, 1H) 7.34 (d, J=8.2 Hz, 1H) 7.89 (s, 1H) 8.25 (s, 1H) 11.78 (br. s., 1H)

LC/MS (method LC-C): R t 3.15 min, MH + 543

[α] D 20 : +141.8° (c 0.3936, DMF)

Chiral SFC (method SFC-C): R t 4.95 min MH + 543, chiral purity 100%,

or a pharmaceutically acceptable salt, solvate or polymorph thereof.

16. A compound according to claim 1 , wherein said compound is:

Enantiomer 4B,

wherein 1 H NMR (500 MHz, DMSO-d 6 ) δ ppm 2.21 (s, 3H) 3.09 (s, 3H) 3.72 (s, 3H) 3.79 (s, 3H) 4.01 (s, 3H) 6.20 (d, J=7.9 Hz, 1H) 6.58 (s, 2H) 6.88-6.93 (m, 2H) 6.96 (dd, J=8.2, 1.9 Hz, 1H) 7.02 (d, J=7.9 Hz, 1H) 7.12 (d, J=1.9 Hz, 1H) 7.34 (d, J=8.2 Hz, 1H) 7.90 (s, 1H) 8.25 (s, 1H) 11.79 (br. s., 1H)

LC/MS (method LC-C): R t 3.15 min, MH + 543

[α] D 20 : 142.2° (c 0.3909, DMF)

Chiral SFC (method SFC-C): R t 6.84 min, MH + 543, chiral purity 100%,

or a pharmaceutically acceptable salt, solvate or polymorph thereof.

17. A compound according to claim 1 , wherein said compound is:

Enantiomer 5A,

wherein 1 H NMR (500 MHz, DMSO-d 6 ) δ ppm 3.09 (s, 3H) 3.72 (s, 3H) 3.85 (s, 3H) 4.00 (s, 3H) 6.21 (d, J=7.9 Hz, 1H) 6.58 (d, J=1.3 Hz, 2H) 6.90 (s, 1H) 6.97 (dd, J=8.2, 2.0 Hz, 1H) 7.07 (d, J=7.9 Hz, 1H) 7.11-7.17 (m, 2H) 7.34 (d, J=8.2 Hz, 1H) 7.82 (d, J=11.7 Hz, 1H) 8.35 (s, 1H) 11.98 (br. s., 1H)

LC/MS (method LC-C): R t 3.00 min, MH + 547

[α] D 20 : +136.4° (c 0.28, DMF)

Chiral SFC (method SFC-B): R t 3.43 min, MH + 547, chiral purity 100%,

or a pharmaceutically acceptable salt, solvate or polymorph thereof.

18. A compound according to claim 1 , wherein said compound is:

Enantiomer 5B,

wherein 1 H NMR (500 MHz, DMSO-d 6 ) δ ppm 3.09 (s, 3H) 3.72 (s, 3H) 3.85 (s, 3H) 4.00 (s, 3H) 6.21 (d, J=7.9 Hz, 1H) 6.58 (d, J=1.3 Hz, 2H) 6.90 (s, 1H) 6.97 (dd, J=8.2, 2.0 Hz, 1H) 7.07 (d, J=7.9 Hz, 1H) 7.11-7.19 (m, 2H) 7.34 (d, J=8.2 Hz, 1H) 7.82 (d, J=11.7 Hz, 1H) 8.35 (s, 1H) 11.95 (br. s., 1H)

LC/MS (method LC-C): R t 3.00 min, MH + 547

[α] D 20 : 126.3° (c 0.2755, DMF)

Chiral SFC (method SFC-B): R t 4.80 min, MH + 547, chiral purity 98.06%,

or a pharmaceutically acceptable salt, solvate or polymorph thereof.

19. A compound according to claim 1 , wherein said compound is:

Enantiomer 6A,

wherein 1 H NMR (360 MHz, DMSO-d 6 ) δ ppm 2.29 (s, 3H) 3.10 (s, 3H) 3.72 (s, 3H) 3.80 (s, 3H) 4.02 (s, 3H) 6.24 (d, J=7.7 Hz, 1H) 6.56-6.59 (m, 1H) 6.59-6.62 (m, 1H) 6.92 (t, J=1.6 Hz, 1H) 6.93-6.99 (m, 2H) 7.06 (d, J=7.7 Hz, 1H) 7.13 (d, J=1.8 Hz, 1H) 7.35 (d, J=8.4 Hz, 1H) 7.94 (d, J=8.4 Hz, 1H) 8.35 (s, 1H) 11.91 (br s, 1H)

LC/MS (method LC-A): R t 1.18 min, MH + 543

[α] D 20 : +122.9° (c 0.48, DMF)

Chiral SFC (method SFC-E): R t 4.15 min MH + 543, chiral purity 100%,

or a pharmaceutically acceptable salt, solvate or polymorph thereof.

20. A compound according to claim 1 , wherein said compound is:

Enantiomer 6B,

wherein 1 H NMR (360 MHz, DMSO-d 6 ) δ ppm 2.29 (s, 3H) 3.10 (s, 3H) 3.72 (s, 3H) 3.80 (s, 3H) 4.02 (s, 3H) 6.24 (d, J=7.7 Hz, 1H) 6.57-6.59 (m, 1H) 6.59-6.62 (m, 1H) 6.92 (t, J=1.8 Hz, 1H) 6.93-7.00 (m, 2H) 7.06 (d, J=7.7 Hz, 1H) 7.13 (d, J=1.8 Hz, 1H) 7.35 (d, J=8.1 Hz, 1H) 7.94 (d, J=8.8 Hz, 1H) 8.35 (d, J=2.2 Hz, 1H) 11.91 (br s, 1H)

LC/MS (method LC-A): R t 1.22 min, MH + 543

[α] D 20 : 120.6° (c 0.2755, DMF)

Chiral SFC (method SFC-E): R t 4.50 min, MH + 543, chiral purity 99.35%,

or a pharmaceutically acceptable salt, solvate or polymorph thereof.

21. A compound according to claim 1 , wherein said compound is:

Enantiomer 7A,

wherein 1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 2.30 (d, J=1.5 Hz, 3H) 3.09 (s, 3H) 3.72 (s, 3H) 4.00 (s, 3H) 6.22 (d, J=7.9 Hz, 1H) 6.56-6.60 (m, 2H) 6.91 (t, J=1.7 Hz, 1H) 6.97 (dd, J=8.3, 2.1 Hz, 1H) 7.01 (d, J=7.7 Hz, 1H) 7.12 (d, J=2.0 Hz, 1H) 7.22 (d, J=10.1 Hz, 1H) 7.34 (d, J=8.1 Hz, 1H) 8.02 (d, J=7.7 Hz, 1H) 8.37 (s, 1H) 11.96 (s, 1H)

LC/MS (method LC-A): R t 1.15 min, MH + 531

[α] D 20 : 163.2° (c 0.435, DMF)

Chiral SFC (method SFC-E): R t 4.26 min, MH + 531, chiral purity 100%,

or a pharmaceutically acceptable salt, solvate or polymorph thereof.

22. A compound according to claim 1 , wherein said compound is:

Enantiomer 7B,

wherein 1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 2.30 (d, J=1.5 Hz, 3H) 3.09 (s, 3H) 3.72 (s, 3H) 4.00 (s, 3H) 6.22 (d, J=7.7 Hz, 1H) 6.57-6.61 (m, 2H) 6.92 (t, J=1.8 Hz, 1H) 6.97 (dd, J=8.1, 2.0 Hz, 1H) 7.01 (d, J=7.7 Hz, 1H) 7.12 (d, J=2.0 Hz, 1H) 7.22 (d, J=10.0 Hz, 1H) 7.35 (d, J=8.4 Hz, 1H) 8.02 (d, J=7.9 Hz, 1H) 8.37 (d, J=2.4 Hz, 1H) 11.97 (s, 1H)

LC/MS (method LC-A): R t 1.15 min, MH + 531

[α] D 20 : +166.6° (c 0.5, DMF)

Chiral SFC (method SFC-E): R t 3.78 min, MH + 531, chiral purity 100%,

or a pharmaceutically acceptable salt, solvate or polymorph thereof.

23. A compound according to claim 1 , wherein said compound is:

Enantiomer 8A,

wherein 1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 3.09 (s, 3H) 3.73 (s, 3H) 3.99 (s, 3H) 6.29 (d, J=7.6 Hz, 1H) 6.60 (br s, 2H) 6.92 (s, 1H) 6.98 (dd, J=8.3, 1.8 Hz, 1H) 7.07 (d, J=8.1 Hz, 1H) 7.13 (d, J=1.5 Hz, 1H) 7.36 (d, J=8.1 Hz, 1H) 7.54 (d, J=8.1 Hz, 1H) 7.69 (d, J=8.6 Hz, 1H) 8.49 (s, 1H) 8.60 (s, 1H) 12.41 (br s, 1H)

LC/MS (method LC-C): R t 3.25 min, MH + 567

[α] D 20 : 119.2° (c 0.2727, DMF)

Chiral SFC (method SFC-F): R t 2.64 min, MH + 567, chiral purity 100%,

or a pharmaceutically acceptable salt, solvate or polymorph thereof.

24. A compound according to claim 1 , wherein said compound is:

Enantiomer 8B,

wherein 1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 3.09 (s, 3H) 3.73 (s, 3H) 3.99 (s, 3H) 6.29 (d, J=8.1 Hz, 1H) 6.60 (s, 2H) 6.92 (s, 1H) 6.98 (dd, J=8.6, 2.0 Hz, 1H) 7.07 (d, J=8.1 Hz, 1H) 7.13 (d, J=2.0 Hz, 1H) 7.36 (d, J=8.6 Hz, 1H) 7.54 (dd, J=8.6, 1.5 Hz, 1H) 7.69 (d, J=8.6 Hz, 1H) 8.49 (s, 1H) 8.60 (s, 1H) 12.40 (br s, 1H)

LC/MS (method LC-C): R t 3.25 min, MH + 567

[α] D 20 : +125.1° (c 0.2455, DMF)

Chiral SFC (method SFC-F): R t 3.44 min, MH + 567, chiral purity 100%,

or a pharmaceutically acceptable salt, solvate or polymorph thereof.

25. A compound according to claim 1 , wherein said compound is:

Enantiomer 10A,

wherein 1 H NMR (360 MHz, DMSO-d 6 ) δ ppm 3.09 (s, 3H) 3.72 (s, 3H) 3.87 (s, 3H) 3.99 (s, 3H) 6.22 (d, J=7.7 Hz, 1H) 6.55-6.59 (m, 2H) 6.88-6.91 (m, 1H) 6.98 (dd, J=8.1, 1.8 Hz, 1H) 7.08 (d, J=7.7 Hz, 1H) 7.13 (d, J=2.2 Hz, 1H) 7.21 (s, 1H) 7.34 (d, J=8.1 Hz, 1H) 8.02 (d, J=1.5 Hz, 1H) 8.41 (s, 1H) 12.05 (br s, 1H)

LC/MS (method LC-A): R t 1.20 min, MH + 613

[α] D 20 : +81.4° (c 0.29, DMF)

Chiral SFC (method SFC-E): R t 3.34 min, MH + 613, chiral purity 100%,

or a pharmaceutically acceptable salt, solvate or polymorph thereof.

26. A compound according to claim 1 , wherein said compound is:

Enantiomer 10B,

wherein 1 H NMR (360 MHz, DMSO-d 6 ) δ ppm 3.09 (s, 3H) 3.72 (s, 3H) 3.87 (s, 3H) 3.99 (s, 3H) 6.22 (d, J=7.7 Hz, 1H) 6.55-6.60 (m, 2H) 6.90 (t, J=1.6 Hz, 1H) 6.98 (dd, J=8.2, 2.0 Hz, 1H) 7.08 (d, J=7.8 Hz, 1H) 7.13 (d, J=2.2 Hz, 1H) 7.21 (s, 1H) 7.34 (d, J=8.4 Hz, 1H) 8.01 (d, J=1.1 Hz, 1H) 8.41 (s, 1H) 12.08 (br s, 1H)

LC/MS (method LC-A): R t 1.20 min, MH + 613

[α] D 20 : −99.6° (c 0.261, DMF)

Chiral SFC (method SFC-E): R t 3.69 min, MH + 613, chiral purity 100%,

or a pharmaceutically acceptable salt, solvate or polymorph thereof.

27. A compound according to claim 1 , wherein said compound is:

Enantiomer 11A,

wherein 1 H NMR (600 MHz, DMSO-d 6 ) δ ppm 2.50 (s, 3H) 3.09 (s, 3H) 3.72 (s, 3H) 4.00 (s, 3H) 6.28 (d, J=7.8 Hz, 1H) 6.56-6.63 (m, 2H) 6.92 (br s, 1H) 6.97 (dd, J=8.4, 1.9 Hz, 1H) 7.05 (br s, 1H) 7.07 (d, J=7.9 Hz, 1H) 7.13 (d, J=1.9 Hz, 1H) 7.35 (d, J=8.4 Hz, 1H) 7.90 (br s, 1H) 8.53 (s, 1H) 12.41 (br s, 1H)

LC/MS (method LC-A): R t 1.26 min, MH + 597

[α] D 20 : +81.3° (c 0.3455, DMF)

Chiral SFC (method SFC-E): R t 2.96 min, MH + 597, chiral purity 100%,

or a pharmaceutically acceptable salt, solvate or polymorph thereof.

28. A compound according to claim 1 , wherein said compound is:

Enantiomer 11,

wherein 1 H NMR (600 MHz, DMSO-d 6 ) δ ppm 2.51 (s, 3H) 3.09 (s, 3H) 3.72 (s, 3H) 4.00 (s, 3H) 6.28 (d, J=7.9 Hz, 1H) 6.58-6.60 (m, 2H) 6.92 (t, J=1.8 Hz, 1H) 6.97 (dd, J=8.4, 1.9 Hz, 1H) 7.05 (br s, 1H) 7.06 (d, J=7.9 Hz, 1H) 7.13 (d, J=2.1 Hz, 1H) 7.35 (d, J=8.2 Hz, 1H) 7.89 (br s, 1H) 8.53 (s, 1H) 12.37 (br s, 1H)

LC/MS (method LC-A): R t 1.26 min, MH + 597

[α] D 20 : −87.4° (c 0.342, DMF)

Chiral SFC (method SFC-E): R t 3.44 min, MH + 597, chiral purity 100%, or a pharmaceutically

acceptable salt, solvate or polymorph thereof.

Assignments (1)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 7, 2026

From: JANSSEN PHARMACEUTICALS, INC.

To: KATHOLIEKE UNIVERSITEIT LEUVEN

Reel/Frame 075932/0967 →

Priority Claims (2)

EP 15166900 · May 8, 2015 · regional

EP 16163342 · Mar 31, 2016 · regional

Continuity (2)

Continuation 15571930

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