IP Library › Granted Patent US 12,268,671
Granted Patent B2
US 12,268,671 · App. 16/066,072 · Granted Apr 8, 2025

IL-8 inhibitors for use in the treatment of chemotherapy-induced peripheral neuropathy

Inventors: Laura Brandolini (L'Aquila, IT); Pier Adelchi Ruffini (Milan, IT); Marcello Allegretti (Rome, IT)
Assignee: DOMPÉ FARMACEUTICI S.P.A.
A61K31/426A61K31/165A61K31/19A61K31/192A61P25/02
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Quick Facts
Patent No.
US 12,268,671
App. No.
16/066,072
Granted
Apr 8, 2025
Kind
B2
Abstract

The present invention relates to IL-8 inhibitor compounds, preferably dual CXCR1/CXCR2 receptor inhibitors, useful in the treatment and/or prevention of chemotherapy-induced neuropathy, preferably in the treatment and/or prevention of chemotherapy-induced peripheral neuropathy (CIPN) or chemotherapy-induced optic neuropathy.

Claims (25)

1. A method of treating and/or preventing chemotherapy-induced neuropathy, wherein the chemotherapy-induced neuropathy is chemotherapy-induced peripheral neuropathy or chemotherapy-induced optic neuropathy and wherein the chemotherapy-induced neuropathy is induced by a chemotherapeutic agent selected from the group consisting of taxanes and platinum based drugs, in a subject in need thereof, comprising administration of an IL-8 inhibitor, wherein the IL-8 inhibitor is a compound of formula (II)

or a pharmaceutically acceptable salt thereof,

wherein:

R4 is linear or branched C 1 -C 6 alkyl, benzoyl, phenoxy, or trifluoromethanesulfonyloxy;

R 5 is H or linear or branched C 1 -C 3 alkyl;

R 6 is linear or branched C 1 -C 6 alkyl or trifluoromethyl.

2. The method according to claim 1 , wherein R 4 is 3-benzoyl, 4-isobutyl or 4-trifluoromethanesulfonyloxy.

3. The method according to claim 1 , wherein R 6 is CH 3 .

4. The method according to claim 1 , which method comprises treating and/or preventing allodynia associated with chemotherapy-induced peripheral neuropathy.

5. The method according to claim 1 , wherein the IL-8 inhibitor is an inhibitor of the activity of IL-8 mediated by the CXCR1 receptor.

6. The method according to claim 1 , wherein the IL-8 inhibitor is an inhibitor of the activity of IL-8 mediated by both the CXCR1 and CXCR2 receptor.

7. The method according to claim 1 , wherein the compound is R-(−)-2-(4-isobutylphenyl) propionyl methanesulfonamide or a pharmaceutically acceptable salt thereof.

8. The method according to claim 7 , wherein the compound is in the form of its lysine in situ salt.

9. The method according to claim 1 , wherein the chemotherapy-induced peripheral neuropathy is induced by a taxane.

10. The method according to claim 9 , wherein the taxane is paclitaxel.

11. The method according to claim 1 , wherein the chemotherapy-induced peripheral neuropathy is induced by a platinum based drug.

12. The method according to claim 11 , wherein the platinum based drug is oxaliplatin.

13. A method of treating and/or preventing chemotherapy-induced neuropathy, wherein the chemotherapy-induced neuropathy is chemotherapy-induced peripheral neuropathy or chemotherapy-induced optic neuropathy and wherein the chemotherapy-induced neuropathy is induced by a chemotherapeutic agent selected from the group consisting of taxanes and platinum based drugs, in a subject in need thereof, comprising administration of an IL-8 inhibitor, wherein the IL-8 inhibitor is a compound of formula (III)

or a pharmaceutically acceptable salt thereof,

wherein

R′ is hydrogen;

R is a residue of formula SO 2 Ra wherein Ra is linear or branched C 1 -C 4 alkyl or halo C 1 -C 3 alkyl.

14. The method according to claim 13 , wherein the chiral carbon atom of the phenylpropionic group is in the R configuration.

15. The method according to claim 14 , wherein the compound is R(−)-2-(4-trifluoromethanesulfonyloxy)phenyl]-N-methanesulfonyl propionamide or a pharmaceutically acceptable salt thereof.

16. The method according to claim 15 , wherein the compound is in the form of its sodium salt.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 15, 2018
From: BRANDOLINI, LAURA; RUFFINI, PIER ADELCHI; ALLEGRETTI, MARCELLO
To: DOMPÉ FARMACEUTICI S.P.A.
Reel/Frame 047166/0354 →
Priority Claims (2)
EP 16151618 · Jan 15, 2016 · regional
EP 16190871 · Sep 27, 2016 · regional
Continuity (1)
Related Publication 20190015391A1 · Jan 17, 2019
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