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

Patent metadata

Field	Value
Publication number	US-12268671-B2
Application number	US-201716066072-A
Country	US
Kind code	B2
Filing date	Jan 13, 2017
Priority date	Jan 15, 2016
Publication date	Apr 8, 2025
Grant date	Apr 8, 2025

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.

First claim

The invention claimed is:

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.

Assignees

• Dompe Farm Spa

Inventors

• Brandolini Laura
• Ruffini Pier Adelchi
• Allegretti Marcello

Classifications

• A61P25/02

  for peripheral neuropathies · CPC title

• A61K31/19

  Carboxylic acids, e.g. valproic acid (salicylic acid A61K31/60) · CPC title

• A61K31/165 Primary

  having aromatic rings, e.g. colchicine, atenolol, progabide · CPC title

• A61P27/02

  Ophthalmic agents · CPC title

• A61K31/18

  Sulfonamides (compounds containing a para-N-benzene-sulfonyl-N- group A61K31/63) · CPC title