IP Library › Granted Patent US 12,172,959

Granted Patent B2

US 12,172,959 · App. 18/490,072 · Granted Dec 24, 2024

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 12,172,959
App. No.: 18/490,072
Granted: Dec 24, 2024
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 (141)

1. A pharmaceutical composition, comprising an enantiomer of a compound which is:

or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients, diluents, or carriers.

2. The pharmaceutical composition of claim 1 , wherein the enantiomer is of a compound which is:

3. The pharmaceutical composition of 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 thereof.

4. The pharmaceutical composition of claim 1 , wherein said compound is Enantiomer 1B

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 thereof.

5. The pharmaceutical composition of 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 thereof.

6. The pharmaceutical composition of 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, 1 H) 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 thereof.

7. The pharmaceutical composition of 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, 1 H) 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 thereof.

8. The pharmaceutical composition of 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, 1 H) 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 : −116.7° (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 thereof.

9. The pharmaceutical composition of 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 thereof.

10. The pharmaceutical composition of 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 thereof.

11. The pharmaceutical composition of 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 thereof.

12. The pharmaceutical composition of 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 thereof.

13. The pharmaceutical composition of claim 9 , 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 thereof.

14. The pharmaceutical composition of 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 thereof.

15. The pharmaceutical composition of 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 thereof.

16. The pharmaceutical composition of 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 thereof.

17. The pharmaceutical composition of 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 thereof.

18. The pharmaceutical composition of claim 1 , wherein said compound is Enantiomer 8B

wherein 1H 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 thereof.

19. The pharmaceutical composition of claim 9 , 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 thereof.

20. The pharmaceutical composition of 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 thereof.

21. The pharmaceutical composition of 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 thereof.

22. The pharmaceutical composition of claim 1 , wherein said compound is Enantiomer 11B

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 thereof.

23. A pharmaceutical composition, comprising compound:

or an enantiomer thereof, and one or more pharmaceutically acceptable excipients, diluents, or carriers.

24. The pharmaceutical composition of claim 23 , wherein said compound is

wherein 1 H NMR (400 MHZ, DMSO-d 6 ) δ ppm 3.09 (s, 3H) 3.73 (s, 3H) 3.99 (s, 3H) 6.26 (d, J=7.9 Hz, 1H) 6.57-6.62 (m, 2H) 6.91 (t, J=1.9 Hz, 1H) 6.98 (dd, J=8.4, 2.0 Hz, 1H) 7.07 (d, J=7.9 Hz, 1H) 7.13 (d, J=2.0 Hz, 1H) 7.22 (dd, J=8.6, 2.2 Hz, 1H) 7.36 (d, J=8.4 Hz, 1H) 7.59 (d, J=8.8 Hz, 1H) 8.06 (d, J=0.9 Hz, 1H) 8.55 (s, 1H) 12.28 (br s, 1H)

LC/MS (method LC-A): R t 1.31 min, MH + 583,

and one or more pharmaceutically acceptable excipients, diluents, or carriers.

25. The pharmaceutical composition of claim 23 , wherein said enantiomer of said compound is Enantiomer 9A

wherein 1 H NMR (400 MHZ, DMSO-d 6 ) δ ppm 3.09 (s, 3H) 3.73 (s, 3H) 3.99 (s, 3H) 6.26 (d, J=7.9 Hz, 1H) 6.55-6.62 (m, 2H) 6.91 (t, J=1.5 Hz, 1H) 6.98 (dd, J=8.4, 2.0 Hz, 1H) 7.07 (d, J=7.9 Hz, 1H) 7.13 (d, J=2.0 Hz, 1H) 7.21 (dd, J=8.8, 1.8 Hz, 1H) 7.36 (d, J=8.4 Hz, 1H) 7.59 (d, J=8.8 Hz, 1H) 8.07 (d, J=0.9 Hz, 1H) 8.55 (s, 1H) 12.29 (br s, 1H)

LC/MS (method LC-A): R t 1.20 min, MH + 583

[α] D 20 : +130.3° (c 0.555, DMF)

Chiral SFC (method SFC-E): R t 3.10 min, MH + 583, chiral purity 100%,

and one or more pharmaceutically acceptable excipients, diluents, or carriers.

26. The pharmaceutical composition of claim 23 , wherein said enantiomer of said compound is Enantiomer 9B

wherein 1 H NMR (400 MHZ, DMSO-d 6 ) δ ppm 3.09 (s, 3H) 3.73 (s, 3H) 3.99 (s, 3H) 6.26 (d, J=7.9 Hz, 1H) 6.56-6.62 (m, 2H) 6.92 (t, J=2.0 Hz, 1H) 6.98 (dd, J=8.1, 2.0 Hz, 1H) 7.07 (d, J=7.9 Hz, 1H) 7.13 (d, J=2.0 Hz, 1H) 7.22 (dd, J=8.8, 1.8 Hz, 1H) 7.36 (d, J=8.4 Hz, 1H) 7.59 (d, J=8.8 Hz, 1H) 8.07 (d, J=0.9 Hz, 1H) 8.55 (s, 1H) 12.30 (br s, 1H)

LC/MS (method LC-A): R t 1.20 min, MH + 583

[α] D 20 : −133.2° (c 0.5, DMF)

Chiral SFC (method SFC-E): R t 3.50 min, MH + 583, chiral purity 100%,

and one or more pharmaceutically acceptable excipients, diluents, or carriers.

27. The pharmaceutical composition of claim 9 , wherein the compound is in the form of a pharmaceutically acceptable salt.

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 (4)

Continuation 17139703 · Dec 31, 2020

Continuation 15930738 · May 13, 2020

Continuation 15571930

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