NZ730996B2 - Carbidopa and l-dopa prodrugs and their use to treat parkinson's disease - Google Patents
Carbidopa and l-dopa prodrugs and their use to treat parkinson's diseaseInfo
- Publication number
- NZ730996B2 NZ730996B2 NZ730996A NZ73099615A NZ730996B2 NZ 730996 B2 NZ730996 B2 NZ 730996B2 NZ 730996 A NZ730996 A NZ 730996A NZ 73099615 A NZ73099615 A NZ 73099615A NZ 730996 B2 NZ730996 B2 NZ 730996B2
- Authority
- NZ
- New Zealand
- Prior art keywords
- compound
- pharmaceutical composition
- pharmaceutically acceptable
- acceptable salt
- alkyl
- Prior art date
Links
- 208000018737 Parkinson disease Diseases 0.000 title claims abstract 4
- 239000000651 prodrug Substances 0.000 title abstract 3
- 229940002612 prodrug Drugs 0.000 title abstract 3
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 title abstract 2
- TZFNLOMSOLWIDK-JTQLQIEISA-N carbidopa (anhydrous) Chemical compound NN[C@@](C(O)=O)(C)CC1=CC=C(O)C(O)=C1 TZFNLOMSOLWIDK-JTQLQIEISA-N 0.000 title abstract 2
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 title 1
- 229960004205 carbidopa Drugs 0.000 title 1
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract 11
- 150000001875 compounds Chemical class 0.000 claims 16
- 150000003839 salts Chemical class 0.000 claims 10
- 229910052739 hydrogen Inorganic materials 0.000 claims 6
- 239000001257 hydrogen Substances 0.000 claims 6
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 3
- 239000003814 drug Substances 0.000 claims 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 3
- 239000000203 mixture Substances 0.000 claims 3
- 230000007935 neutral effect Effects 0.000 claims 2
- 238000007920 subcutaneous administration Methods 0.000 claims 2
- 125000000217 alkyl group Chemical group 0.000 claims 1
- 239000007864 aqueous solution Substances 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 238000001802 infusion Methods 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 claims 1
- 238000009118 salvage therapy Methods 0.000 claims 1
- 239000000243 solution Substances 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
-
- 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
- A61K31/66—Phosphorus compounds
- A61K31/661—Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion or mevinphos
-
- 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
- A61K31/66—Phosphorus compounds
- A61K31/661—Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion or mevinphos
- A61K31/6615—Compounds having two or more esterified phosphorus acid groups, e.g. inositol triphosphate, phytic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C281/00—Derivatives of carbonic acid containing functional groups covered by groups C07C269/00 - C07C279/00 in which at least one nitrogen atom of these functional groups is further bound to another nitrogen atom not being part of a nitro or nitroso group
- C07C281/02—Compounds containing any of the groups, e.g. carbazates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/01—Sulfonic acids
- C07C309/02—Sulfonic acids having sulfo groups bound to acyclic carbon atoms
- C07C309/24—Sulfonic acids having sulfo groups bound to acyclic carbon atoms of a carbon skeleton containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C47/00—Compounds having —CHO groups
- C07C47/20—Unsaturated compounds having —CHO groups bound to acyclic carbon atoms
- C07C47/277—Unsaturated compounds having —CHO groups bound to acyclic carbon atoms containing ether groups, groups, groups, or groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/09—Esters of phosphoric acids
- C07F9/094—Esters of phosphoric acids with arylalkanols
Abstract
The present disclosure relates to pharmaceutical compositions comprising a phosphorylated carbidopa prodrug and a phosphorylated L-dopa prodrug, and the use thereof in the treatment of Parkinson's disease and associated conditions.
Claims (15)
1. A pharmaceutical composition comprising a first compound corresponding in structure to Formula (I): R2O NH2 (I) , or a pharmaceutically acceptable salt thereof, wherein R1 and R2 are each ndently ed from the group consisting of hydrogen, -P(O)(OH)2, and –R5–O– P(O)(OH)2; R5 is a alkyl; R6 is hydrogen or a C1-C4-alkyl; and provided that at least one of R1 and R2 is -P(O)(OH)2 or –R5–O–P(O)(OH)2; and a second compound corresponding in structure Formula (II): R4O (II) , or a pharmaceutically acceptable salt thereof, wherein R3 and R4 are each independently selected from the group consisting of hydrogen, -P(O)(OH)2, and –R5–O– P(O)(OH)2; R5 is a C1-C4-alkyl; R6 is hydrogen or a C1-C4-alkyl; and provided that at least one of R3 and R4 is -P(O)(OH)2 or –R5–O–P(O)(OH)2.
2. The pharmaceutical ition of Claim 1, wherein the first compound is O O HO P O HO NH2 (I-a) , HO P O NH2 OH (I-b) , HO O HO OH O HN O NH2 OH (I-c) , O HN HO P O O NH2 OH OH (I-d), HO NH2 O P OH HO (I-e), or HO H2N HO O (I-f).
3. The pharmaceutical composition of Claim 1 or 2 wherein the first compound is a compound corresponding in ure to Formula (I-b): HO P O NH2 OH (I-b) , or a pharmaceutically acceptable salt thereof.
4. The pharmaceutical composition of any one of Claims 1-3, wherein the second compound is O O HO P O HO (II-a) , HO P O OH (II-b) , HO O HO OH O NH2 OH (II-c) , HO P OH O HO (II-d), or HO P OH O (II-e).
5. The pharmaceutical composition of any one of Claims 1-4, wherein the second nd is a compound corresponding in structure to Formula (II-b): HO P O OH (II-b) , or a pharmaceutically acceptable salt thereof.
6. The pharmaceutical composition of any one of Claims 1-5, further comprising a pharmaceutically able carrier.
7. The pharmaceutical composition of any one of Claims 1-6, wherein the first compound or pharmaceutically acceptable salt thereof has a solubility of at least about 200 mg/ml in aqueous solution at about neutral pH, and the second compound or pharmaceutically acceptable salt thereof has a lity of at least about 400 mg/ml in s solution at about neutral pH.
8. The pharmaceutical composition of any one of Claims 1-7, wherein the composition r comprises water and is suitable for infusion.
9. The pharmaceutical composition of any one of Claims 1-8, wherein the combination is an aqueous combination suitable for subcutaneous administration.
10. The pharmaceutical composition of claim 1, comprising a first compound corresponding in structure to Formula (I-b): HO P O NH2 OH (I-b) , or a pharmaceutically able salt thereof; and a second compound corresponding in structure to Formula (II-b): HO P O OH (II-b) , or a pharmaceutically acceptable salt f; wherein the composition is an aqueous composition suitable for subcutaneous administration.
11. Use of the pharmaceutical composition of any one of Claims 1-10 in the manufacture of a medicament for treating Parkinson’s disease in a human subject in need thereof and/or providing rescue therapy in a human subject having Parkinson’s disease.
12. The use of Claim 11, wherein the medicament is formulated to have substantially continuous administration of the first compound and the second compound over a period of at least about 12 hours.
13. The use of Claim 11 or 12, wherein the medicament is formulated to be administered with another arkinson’s agent.
14. A compound corresponding in structure to a (I): R2O NH2 (I) , or a pharmaceutically acceptable salt thereof, n R1 and R2 are each independently selected from the group consisting of hydrogen, -P(O)(OH)2, and –R5–O– P(O)(OH)2; R5 is a C1-C4-alkyl; R6 is hydrogen or a C1-C4-alkyl; and provided that at least one of R1 and R2 is -P(O)(OH)2 or P(O)(OH)2.
15. The compound or salt of Claim 14, wherein the compound corresponds in structure to a (I-b): HO P O NH2 OH (I-b) . AbbVie Inc. By the Attorneys for the Applicant SPRUSON & FERGUSON
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NZ769153A NZ769153B2 (en) | 2015-10-21 | Carbidopa and L-dopa prodrugs and their use to treat Parkinson's disease |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201462066771P | 2014-10-21 | 2014-10-21 | |
| PCT/US2015/056686 WO2016065019A1 (en) | 2014-10-21 | 2015-10-21 | Carbidopa and l-dopa prodrugs and their use to treat parkinson's disease |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NZ730996A NZ730996A (en) | 2024-04-26 |
| NZ730996B2 true NZ730996B2 (en) | 2024-07-30 |
Family
ID=
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TN2022000039A1 (en) | Pyrazolo[3,4-b]pyrazine shp2 phosphatase inhibitors | |
| ZA202403388B (en) | Small molecules for treatement of cancer | |
| HRP20191285T1 (en) | PREPARATIONS OF CARBIDOP AND L-DOPA AND THEIR USE FOR THE TREATMENT OF PARKINSON'S DISEASE | |
| EA201590371A1 (en) | 1,4-DESIGNED PYRIDAZIN ANALOGUES AND METHODS OF TREATMENT RELATED TO SMN DEFICIENCY CONDITIONS | |
| EA201291348A1 (en) | ACTIVATORS OF SOLUBLE GUANYLATZYCLASES | |
| MXPA01006474A (en) | Colchinol derivatives as vascular damaging agents. | |
| MX379425B (en) | 7-benzyl-4-(2-methylbenzyl)-2,4,6,7,8,9-hexahydroimidazo [1,2-a]pyrido[3,4-e]pyrimidin-5(1h)-one, analogs and salts thereof and their use in therapy | |
| MY180666A (en) | Substituted pyrazolo [3,4-b] pyridines as medicaments | |
| GEP20156417B (en) | Pyrrolo [2,3-d] pyrimidine derivatives as inhibitors of tropomyosin-related kinases | |
| NZ613219A (en) | Heterocyclic containing entities, compositions and methods | |
| MX2010013682A (en) | Tricyclic 2,4-diamin0-l,3,5-triazine derivatives useful for the treatment of cancer and myeloproliferative disorders. | |
| MX2010007523A (en) | Novel pyrazolo [3, 4 -d] pyrimidine derivatives as anti -cancer agents. | |
| IN2014MN01577A (en) | ||
| TN2012000249A1 (en) | Pyrazine derivatives and their use in the treatment of neurological disorders | |
| MY179527A (en) | Catecholamine derivatives useful for the treatment of parkinson's disease | |
| JOP20230252A1 (en) | Phosphorus derivatives as novel SOS1 inhibitors | |
| MX2011009709A (en) | Compounds for treating inflammation and pain. | |
| MX2019010756A (en) | Novel imidazo[4,5-c]quinoline derivatives as lrrk2 inhibitors. | |
| PH12021552533A1 (en) | Hexahydro-1h-pyrazino[1,2-a]pyrazine compounds for the treatment of autoimmune disease | |
| PH12014500065A1 (en) | A new therapeutical composition containing apomorphine as active ingredient | |
| MX2021006156A (en) | Compounds useful in hiv therapy. | |
| MX2023009961A (en) | Antiviral heterocyclic compounds. | |
| WO2007035620A3 (en) | Carbazole derivatives | |
| MX2025011886A (en) | Semi-saturated bicyclic derivatives and related uses | |
| MX379704B (en) | 6,7-dihydro-5h-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide compounds |