Granted Patent B2

US 12,209,094 · App. 18/362,028 · Granted Jan 28, 2025

Inventors: Heiner Ebel (Biberach an der Riss, DE); Sara Frattini (Castelleone, IT); Kai Gerlach (Mittelbiberach, DE); Riccardo Giovannini (Verona, IT); Christoph Hoenke (Biberach an der Riss, DE); Rocco Mazzaferro (San Giuliano Milanese, IT); Marco Santagostino (Mittelbiberach, DE); Stefan Scheuerer (Warthausen, DE); Christofer Tautermann (Ingelheim Am Rhein, DE); Thomas Trieselmann (Biberach, DE)

Assignee: Centrexion Therapeutics Corporation

C07D491/107A61P25/00A61P25/02A61P25/04A61P29/00C07D405/14

Abstract

Claims (31)

1. A method for treating a neurologic disease selected from inflammatory and neuropathic pain, comprising orally administering to a human patient an effective amount of a compound of Formula I to treat the neurologic disease, wherein Formula I is represented by:

or a salt thereof; wherein:

R 1 is a group selected from among —H or —C 1 -C 4 -alkyl;

R 7 is phenyl optionally substituted with one or more groups selected from among —CF 3 , —O—CF 3 , —CN, —C 1 -C 6 -alkyl, —C(CH 3 ) 2 —CN, and halogen;

R 2 is selected from among —H or —C 1 -C 4 -alkyl;

R 3 is selected from among —H or -methyl;

n is 1, 2, or 3;

G and E are N;

Z is C;

R 4 denotes —H, and R 5 is -L 1 -R 18 , wherein L 1 is —NH—, —N(C 1 -C 4 -alkyl)-, or a bond, and R 18 is —C 3 -C 8 -cycloalkyl or —C 3 -C 8 -heterocyclyl, wherein R 18 is optionally substituted by one or more groups selected from among halogen, —CF 3 , —OCF 3 , —CN, —OH, —O—C 1 -C 4 -alkyl, —C 1 -C 6 -alkyl, —NH—C(O)—C 1 -C 6 -alkyl, —N(C 1 -C 4 -alkyl)-C(O)—C 1 -C 6 -alkyl, and —C(O)—C 1 -C 6 -alkyl; and

R 6 is -H.

2. The method of claim 1 , wherein L 1 is —NH—.

3. The method of claim 2 , wherein R 18 is —C 3 -C 8 -heterocyclyl substituted by one or more groups selected from among halogen, —CF 3 , —OCF 3 , —CN, —OH, —O—C 1 -C 4 -alkyl, and —C 1 -C 6 -alkyl.

4. The method of claim 1 , wherein the neurologic disease is inflammatory pain.

5. The method of claim 1 , wherein the neurologic disease is neuropathic pain.

6. The method of claim 5 , wherein the neuropathic pain is low back pain, hip pain, leg pain, non-herpetic neuralgia, post herpetic neuralgia, diabetic neuropathy, nerve injury-induced pain, phantom limb pain, post-surgical pain, stump pain, or trigeminal neuralgia.

7. The method of claim 3 , wherein the neurologic disease is neuropathic pain.

8. The method of claim 7 , wherein the neuropathic pain is low back pain, hip pain, leg pain, non-herpetic neuralgia, post herpetic neuralgia, diabetic neuropathy, nerve injury-induced pain, phantom limb pain, post-surgical pain, stump pain, or trigeminal neuralgia.

9. A method for treating a neurologic disease selected from inflammatory and neuropathic pain, comprising orally administering to a human patient an effective amount of a compound of Formula I to treat the neurologic disease, wherein Formula I is represented by

or a salt thereof.

10. The method of claim 9 , wherein the neurologic disease is inflammatory pain.

11. The method of claim 9 , wherein the neurologic disease is neuropathic pain.

12. The method of claim 11 , wherein the neuropathic pain is low back pain, hip pain, leg pain, non-herpetic neuralgia, post herpetic neuralgia, diabetic neuropathy, nerve injury-induced pain, phantom limb pain, post-surgical pain, stump pain, or trigeminal neuralgia.

13. The method of claim 11 , wherein the neuropathic pain is low back pain.

14. The method of claim 11 , wherein the neuropathic pain is hip pain.

15. The method of claim 11 , wherein the neuropathic pain is leg pain.

16. The method of claim 11 , wherein the neuropathic pain is non-herpetic neuralgia or post herpetic neuralgia.

17. The method of claim 11 , wherein the neuropathic pain is diabetic neuropathy.

18. The method of claim 11 , wherein the neuropathic pain is nerve injury-induced pain.

19. The method of claim 11 , wherein the neuropathic pain is trigeminal neuralgia.

20. The method of claim 9 , wherein the neurologic disease is neuropathic pain due to chemotherapy caused nerve injury.

Assignments (3)

Priority Claims (2)

Continuity (6)

References Cited (251)