NZ765220B2 - Use of riluzole prodrugs to treat ataxias - Google Patents
Use of riluzole prodrugs to treat ataxias Download PDFInfo
- Publication number
- NZ765220B2 NZ765220B2 NZ765220A NZ76522018A NZ765220B2 NZ 765220 B2 NZ765220 B2 NZ 765220B2 NZ 765220 A NZ765220 A NZ 765220A NZ 76522018 A NZ76522018 A NZ 76522018A NZ 765220 B2 NZ765220 B2 NZ 765220B2
- Authority
- NZ
- New Zealand
- Prior art keywords
- patient
- administered
- riluzole prodrug
- riluzole
- prodrug
- Prior art date
Links
- FTALBRSUTCGOEG-UHFFFAOYSA-N Riluzole Chemical compound C1=C(OC(F)(F)F)C=C2SC(N)=NC2=C1 FTALBRSUTCGOEG-UHFFFAOYSA-N 0.000 title claims abstract 15
- 239000000651 prodrug Substances 0.000 title claims abstract 15
- 229940002612 prodrug Drugs 0.000 title claims abstract 15
- 229960004181 riluzole Drugs 0.000 title claims abstract 15
- 206010003591 Ataxia Diseases 0.000 title claims abstract 5
- 208000009415 Spinocerebellar Ataxias Diseases 0.000 claims 2
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims 2
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims 1
- 102000007372 Ataxin-1 Human genes 0.000 claims 1
- 108010032963 Ataxin-1 Proteins 0.000 claims 1
- 102000014461 Ataxins Human genes 0.000 claims 1
- 108010078286 Ataxins Proteins 0.000 claims 1
- 206010008025 Cerebellar ataxia Diseases 0.000 claims 1
- 108091026890 Coding region Proteins 0.000 claims 1
- 201000004562 autosomal dominant cerebellar ataxia Diseases 0.000 claims 1
- 239000002775 capsule Substances 0.000 claims 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 150000003839 salts Chemical class 0.000 claims 1
- 201000003624 spinocerebellar ataxia type 1 Diseases 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- YBZSGIWIPOUSHY-UHFFFAOYSA-N troriluzole Chemical compound NCC(=O)NCC(N(CC(NC=1SC2=C(N=1)C=CC(=C2)OC(F)(F)F)=O)C)=O YBZSGIWIPOUSHY-UHFFFAOYSA-N 0.000 abstract 1
- 229940121629 troriluzole Drugs 0.000 abstract 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/428—Thiazoles condensed with carbocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2063—Proteins, e.g. gelatin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/485—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/68—Benzothiazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D277/82—Nitrogen atoms
Abstract
Disclosed are methods of treating ataxia by administering to a patient in need thereof a riluzole prodrug such as troriluzole. Pharmaceutical compositions including the riluzole prodrugs are also disclosed.
Claims (14)
1. A use of a riluzole prodrug in the manufacture of a medicament for treating ataxia in a patient in need thereof, wherein the ataxia is Spinocerebellar ataxia selected from SCA1, SCA2, SCA3, SCA6, SCA7, SCA8 and SCA10, wherein the riluzole prodrug has the following formula: and pharmaceutically acceptable salts thereof, wherein: R is selected from the group consisting H, CH , CH CH , CH CH CH , CH CCH, CH(CH ) , 23 3 2 3 2 2 3 2 3 2 CH CH(CH ) , CH(CH )CH CH , CH OH, CH OCH Ph, CH CH OCH Ph, CH(OH)CH , CH Ph, 2 3 2 3 2 3 2 2 2 2 2 2 3 2 CH (cyclohexyl), CH (4-OH-Ph), (CH ) NH , (CH ) NHC(NH )NH, CH (3-indole), CH (5-imidazole), 2 2 2 4 2 2 3 2 2 2 CH CO H, CH CH CO H, CH CONH , and CH CH CONH . 2 2 2 2 2 2 2 2 2 2
2. The use of claim 1, wherein the ataxia is associated with translated GAG repeat expansions or untranslated repeat expansions in non-coding regions.
3. The use of claim 1, wherein the riluzole prodrug has the following formula:
4. The use of claim 1, wherein the treatment provides an improvement in the patient’s total SARA score of at least 0.8, or 0.9, or 1.0, or 1.1, or 1.2, or 1.3, or 1.4, or 1.5, or 1.6, or 1.7, or 1.8, or 1.9, or 2.0, or greater.
5. The use of claim 1, wherein the riluzole prodrug is to be administered to the patient at a dosage of from about 17.5 to 200 mg per day.
6. The use of claim 5, wherein the riluzole prodrug is to be administered to the patient at a dosage of about 17.5, or 35, or 70, or 100, or 140, or 200 mg per day.
7. The use of claim 6, wherein the riluzole prodrug is to be administered to the patient at a dosage of 200 mg, once per day.
8. The use of claim 6, wherein the riluzole prodrug is to be administered to the patient at a dosage of 140 mg, once per day.
9. The use of claim 1, wherein the riluzole prodrug is to be administered to the patient once per
10. The use of claim 1, wherein the riluzole prodrug is to be administered to the patient twice per
11. The use of claim 1, wherein the riluzole prodrug is to be administered to the patient in the form of a capsule.
12. The use of claim 1, wherein the riluzole prodrug is to be administered to the patient in the form of a tablet.
13. The use of claim 1, wherein the riluzole prodrug is to be administered to the patient for a duration of from about 8 weeks to 48 weeks.
14. The use as claimed in any one of claims 1-13 substantially as described herein and with reference to any example thereof.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762584856P | 2017-11-12 | 2017-11-12 | |
| US201862717948P | 2018-08-13 | 2018-08-13 | |
| PCT/US2018/060232 WO2019094851A1 (en) | 2017-11-12 | 2018-11-11 | Use of riluzole prodrugs to treat ataxias |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NZ765220A NZ765220A (en) | 2023-11-24 |
| NZ765220B2 true NZ765220B2 (en) | 2024-02-27 |
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