Crystalline forms of compounds for preventing or treating sensory hair cell death

Patent metadata

Field	Value
Publication number	US-11779573-B2
Application number	US-201816642877-A
Country	US
Kind code	B2
Filing date	Aug 31, 2018
Priority date	Sep 1, 2017
Publication date	Oct 10, 2023
Grant date	Oct 10, 2023

Abstract

Described herein is (4R,7,S)-2-(3-(4-chlorophenyl)ureido)-9-methyl-5,6,7,8-tetrahydro-4H-4,7-epiminocyclohepta[b]thiophene-3-carboxamide mesylate, including crystalline forms and solvates thereof.

First claim

We claim:

1. A crystalline form of a mesylate salt of (4R,7S)-2-(3-(4-chlorophenyl)ureido)-9-methyl-5,6,7,8-tetrahydro-4H-4,7-epiminocyclohepta[b]thiophene-3-carboxamide, wherein the mesylate salt has an X-ray powder diffraction (XRPD) pattern with characteristic peaks at 7.6° 2-Theta, 10.6° 2-Theta, 15.0° 2-Theta, 16.0° 2-Theta, 16.8° 2-Theta, 17.7° 2-Theta, 21.9° 2-Theta, and 22.5° 2-Theta.

2. The crystalline form of claim 1 , wherein the crystalline form is unsolvated.

3. The crystalline form of claim 1 , wherein the crystalline form is anhydrous.

4. A pharmaceutical composition comprising the crystalline form of claim 1 , and at least one inactive ingredient selected from pharmaceutically acceptable carriers, diluents, and excipients.

5. The pharmaceutical composition of claim 4 further comprising an aminoglycoside antibiotic.

6. The pharmaceutical composition of claim 5 wherein the aminoglycoside antibiotic is selected from streptomycin, neomycin, framycetin, paromomycin, paromomycin sulfate, ribostamycin, kanamycin, amikacin, arbekacin, bekanamycin, dibekacin, tobramycin, spectinomycin, hygromycin B, gentamicin, netilmicin, sisomicin, isepamicin, verdamicin, and astromicin.

7. A method for protecting against kidney damage in an individual receiving an aminoglycoside antibiotic comprising administering to the individual a therapeutically effective amount of a crystalline form of claim 1 .

8. A method for treating hearing loss in an individual comprising administering to the individual a therapeutically effective amount of a crystalline form of claim 1 .

9. A method for treating sensory hair cell death in an individual comprising administering to the individual a therapeutically effective amount of a crystalline form of claim 1 .

10. The method of claim 8 wherein the hearing loss is associated with exposure to an ototoxic agent.

11. The method of claim 9 wherein the sensory hair cell death is associated with exposure to an ototoxic agent.

12. The method of claim 10 wherein the ototoxic agent is an aminoglycoside antibiotic, chemotherapeutic agent, loop diuretic, antimalarial sesquiterpene lactone endoperoxide, antimalarial quinine, salicylate, or interferon polypeptide.

13. The method of claim 7 , wherein the aminoglycoside antibiotic is selected from streptomycin, neomycin, framycetin, paromomycin, paromomycin sulfate, ribostamycin, kanamycin, amikacin, arbekacin, bekanamycin, dibekacin, tobramycin, spectinomycin, hygromycin B, gentamicin, netilmicin, sisomicin, isepamicin, verdamicin, and astromicin.

14. The method of claim 12 , wherein the aminoglycoside antibiotic is selected from streptomycin, neomycin, framycetin, paromomycin, paromomycin sulfate, ribostamycin, kanamycin, amikacin, arbekacin, bekanamycin, dibekacin, tobramycin, spectinomycin, hygromycin B, gentamicin, netilmicin, sisomicin, isepamicin, verdamicin, and astromicin.

15. The method of claim 11 wherein the ototoxic agent is an aminoglycoside antibiotic, chemotherapeutic agent, loop diuretic, antimalarial sesquiterpene lactone endoperoxide, antimalarial quinine, salicylate, or interferon polypeptide.

16. The method of claim 15 , wherein the aminoglycoside antibiotic is selected from streptomycin, neomycin, framycetin, paromomycin, paromomycin sulfate, ribostamycin, kanamycin, amikacin, arbekacin, bekanamycin, dibekacin, tobramycin, spectinomycin, hygromycin B, gentamicin, netilmicin, sisomicin, isepamicin, verdamicin, and astromicin.

Assignees

• Univ Washington

Inventors

• Johnson Graham
• Aret Edwin
• Tchesnokov Alexei

Classifications

• A61K31/439 Primary

  the ring forming part of a bridged ring system, e.g. quinuclidine (8-azabicyclo [3.2.1] octanes A61K31/46) · CPC title

• A61K31/702

  Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages · CPC title

• C07D495/18 Primary

  Bridged systems · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61P25/18 Primary

  Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia · CPC title