IL-8 inihibitors for use in the treatment of some urological disorders

Patent metadata

Field	Value
Publication number	US-12150933-B2
Application number	US-201615743721-A
Country	US
Kind code	B2
Filing date	Jul 12, 2016
Priority date	Jul 14, 2015
Publication date	Nov 26, 2024
Grant date	Nov 26, 2024

Abstract

The present invention relates to IL-8 inhibitor compounds, preferably dual CXCR1/CXCR2 receptor inhibitors, useful in the treatment and/or prevention of interstitial cystitis/painful bladder syndrome (IC/PBS) and/or over active bladder (OAB), also including IC/PBS and/or OAB induced by anticancer therapy. Methods of treatment and/or prevention, combinations and kits comprising said IL-8 inhibitors are also covered therein.

First claim

The invention claimed is:

1. A method of treating interstitial cystitis/painful bladder syndrome (IC/PBS) and/or over active bladder (OAB) in a subject in need thereof, comprising administration of an effective amount of a CXCR1 inhibitor or a dual CXCR1 and CXCR2 inhibitor, wherein the CXCR1 inhibitor or dual CXCR1 and CXCR2 inhibitor is a compound of formula (I)

wherein
R1 is hydrogen;
X is OH;
R2 is hydrogen or linear C 1 -C 4 alkyl;
Y is a heteroatom selected from S, O and N; and
Z is selected from linear or branched C 1 -C 4 alkyl, linear or branched C 1 -C 4 alkoxy, halo C 1 -C 3 alkyl and halo C 1 -C 3 alkoxy;
or a pharmaceutically acceptable salt thereof.

2. The method according to claim 1 , wherein the IC/PBS and/or over active bladder (OAB) is induced by anticancer therapy or radiotherapy to the pelvis.

3. The method according to claim 1 , wherein the compound of formula (I) is selected from (R,S)-2-(4-{[4-(trifluoromethyl)-1,3-thiazol-2-yl]amino}phenyl)propanoic acid and (2S)-2-(4-{[4-(trifluoromethyl)-1,3-thiazol-2-yl] amino} phenyl) propanoic acid, or a sodium salt thereof.

4. The method according to claim 1 , wherein the compound of formula (I) is administered as a pharmaceutical composition comprising the compound of formula (I) and at least one pharmaceutically acceptable excipient.

5. The method according to claim 4 , wherein the pharmaceutical composition further comprises at least one further pharmaceutically active compound.

6. The method according to claim 5 , wherein the further pharmaceutically active compound is an active compound useful for the prevention and treatment of IC/PBS and/or OAB.

7. The method according to claim 6 , wherein the further pharmaceutically active compound is a TRPV1 antagonist.

8. The method according to claim 5 , wherein the further pharmaceutically active compound is a drug that induces, as an undesired effect, IC/PBS or OAB.

9. The method according to claim 8 , wherein the further pharmaceutically active compound is selected from cyclophosphamide, Bacillus Calmette-Guérin to be instilled directly into the bladder, mitomycin C, Adriamycin or tiaprofenic acid.

10. A method of preventing interstitial cystitis/painful bladder syndrome (IC/PBS) and/or over active bladder (OAB), wherein the IC/PBS and/or OAB is induced by anticancer therapy or radiotherapy to the pelvis, in a subject undergoing anticancer therapy or radiotherapy to the pelvis, comprising administration of an effective amount of a CXCR1 inhibitor or a dual CXCR1 and CXCR2 inhibitor, wherein the CXCR1 inhibitor or dual CXCR1 and CXCR2 inhibitor is a compound of formula (I)

wherein
R1 is hydrogen;
X is OH;
R2 is hydrogen or linear C 1 -C 4 alkyl;
Y is a heteroatom selected from S, O and N; and
Z is selected from linear or branched C 1 -C 4 alkyl, linear or branched C 1 -C 4 alkoxy, halo C 1 -C 3 alkyl and halo C 1 -C 3 alkoxy;
or a pharmaceutically acceptable salt thereof.

11. The method according to claim 10 , wherein the compound of formula (I) is selected from (R,S)-2-(4-{[4-(trifluoromethyl)-1,3-thiazol-2-yl]amino}phenyl)propanoic acid and (2S)-2-(4-{[4-(trifluoromethyl)-1,3-thiazol-2-yl]amino}phenyl)propanoic acid, or a sodium salt thereof.

12. The method according to claim 10 , the compound of formula (I) is is administered as a pharmaceutical composition comprising the compound of formula (I) and at least one pharmaceutically acceptable excipient.

13. The method according to claim 12 , wherein the pharmaceutical composition further comprises at least one further pharmaceutically active compound.

14. The method according to claim 13 , wherein the further pharmaceutically active compound is an active compound useful for the prevention and treatment of IC/PBS and/or OAB.

15. The method according to claim 14 wherein the further pharmaceutically active compound is a TRPV1 antagonist.

16. The method according to claim 13 , wherein the further pharmaceutically active compound is a drug that induces, as an undesired effect, IC/PBS or OAB.

17. The method according to claim 16 , wherein the further pharmaceutically active compound is selected from cyclophosphamide, Bacillus Calmette-Guérin to be instilled directly into the bladder, mitomycin C, Adriamycin or tiaprofenic acid.

Assignees

• Dompe Farm Spa

Inventors

• Allegretti Marcello
• Aramini Andrea
• Cesta Maria Candida
• Bianchini Gianluca
• Brandolini Laura
• Angelico Patrizia

Classifications

• A61K31/664

  Amides of phosphorus acids · CPC title

• A61P13/10

  of the bladder · CPC title

• A61K2300/00

  Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00 · CPC title

• A61K31/407

  condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine · CPC title

• A61K31/381

  having five-membered rings · CPC title