IP Library › Granted Patent US 11,827,602

Granted Patent B2

US 11,827,602 · App. 17/139,703 · Granted Nov 28, 2023

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 11,827,602
App. No.: 17/139,703
Granted: Nov 28, 2023
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 (145)

1. A method of inhibiting Dengue viral replication in an animal cell, comprising administering to the animal cell 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 or OCF 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. The method of claim 1 , wherein the animal cell is a mammalian cell.

3. The method of claim 1 , wherein the animal cell is a human cell.

4. The method of claim 1 , wherein the compound is administered to the cell prior to being infected with Dengue virus.

5. The method of claim 1 , further comprising administering another antiviral agent to the cell.

6. The method of claim 1 , wherein said compound is selected from the group consisting of:

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

7. The method of claim 1 , wherein said compound is selected from the group consisting of:

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%,

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%,

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%,

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%,

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%,

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%,

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%,

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%,

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%,

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%,

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%,

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%,

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%,

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%,

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%,

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%,

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%,

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%,

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,

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%,

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%, and

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, solvate or polymorph thereof.

8. The method of claim 1 , wherein said compound is:

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

9. The method of claim 1 , wherein said compound is:

Enantiomer 9A,

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%,

or a pharmaceutically acceptable salt, solvate or polymorph thereof.

10. The method of claim 1 , wherein said compound is:

Enantiomer 9B,

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%,

or a pharmaceutically acceptable salt, solvate or polymorph thereof.

11. The method of claim 1 , wherein said compound is administered in the form of a pharmaceutical composition comprising the compound or the stereoisomer, pharmaceutically acceptable salt, solvate or polymorph thereof, and one or more pharmaceutically acceptable excipients, diluents or carriers.

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 (3)

Continuation 15930738 · May 13, 2020

Continuation 15571930

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