TWI772382B - 氘代丁苯那嗪(deutetrabenazine)之類似物、其製備方法及用途 - Google Patents
氘代丁苯那嗪(deutetrabenazine)之類似物、其製備方法及用途 Download PDFInfo
- Publication number
- TWI772382B TWI772382B TW107108832A TW107108832A TWI772382B TW I772382 B TWI772382 B TW I772382B TW 107108832 A TW107108832 A TW 107108832A TW 107108832 A TW107108832 A TW 107108832A TW I772382 B TWI772382 B TW I772382B
- Authority
- TW
- Taiwan
- Prior art keywords
- compound
- deuterated tetrabenazine
- concentration
- pharmaceutical composition
- tetrabenazine
- Prior art date
Links
- MKJIEFSOBYUXJB-VFJJUKLQSA-N (3r,11br)-3-(2-methylpropyl)-9,10-bis(trideuteriomethoxy)-1,3,4,6,7,11b-hexahydrobenzo[a]quinolizin-2-one Chemical compound C1CN2C[C@@H](CC(C)C)C(=O)C[C@@H]2C2=C1C=C(OC([2H])([2H])[2H])C(OC([2H])([2H])[2H])=C2 MKJIEFSOBYUXJB-VFJJUKLQSA-N 0.000 title abstract description 5
- 229950005031 deutetrabenazine Drugs 0.000 title abstract description 3
- 238000002360 preparation method Methods 0.000 title description 8
- 238000000034 method Methods 0.000 claims abstract description 144
- 239000000203 mixture Substances 0.000 claims abstract description 49
- MKJIEFSOBYUXJB-HOCLYGCPSA-N (3S,11bS)-9,10-dimethoxy-3-isobutyl-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-one Chemical class C1CN2C[C@H](CC(C)C)C(=O)C[C@H]2C2=C1C=C(OC)C(OC)=C2 MKJIEFSOBYUXJB-HOCLYGCPSA-N 0.000 claims description 296
- 239000008194 pharmaceutical composition Substances 0.000 claims description 130
- 229940125782 compound 2 Drugs 0.000 claims description 101
- 239000003814 drug Substances 0.000 claims description 49
- 229940079593 drug Drugs 0.000 claims description 34
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 32
- 229910052805 deuterium Inorganic materials 0.000 claims description 32
- 239000007937 lozenge Substances 0.000 claims description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 18
- 208000000269 Hyperkinesis Diseases 0.000 claims description 11
- 229960005333 tetrabenazine Drugs 0.000 claims description 11
- 239000003937 drug carrier Substances 0.000 claims description 10
- 208000023105 Huntington disease Diseases 0.000 claims description 7
- 238000003860 storage Methods 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 206010008748 Chorea Diseases 0.000 claims description 3
- 201000004311 Gilles de la Tourette syndrome Diseases 0.000 claims description 3
- 208000000323 Tourette Syndrome Diseases 0.000 claims description 3
- 208000016620 Tourette disease Diseases 0.000 claims description 3
- 208000012601 choreatic disease Diseases 0.000 claims description 3
- 206010043118 Tardive Dyskinesia Diseases 0.000 claims description 2
- 238000004128 high performance liquid chromatography Methods 0.000 claims 9
- 239000003826 tablet Substances 0.000 claims 3
- 206010010904 Convulsion Diseases 0.000 claims 1
- 208000012661 Dyskinesia Diseases 0.000 claims 1
- 230000036461 convulsion Effects 0.000 claims 1
- 230000001660 hyperkinetic effect Effects 0.000 claims 1
- 229940125904 compound 1 Drugs 0.000 description 97
- 150000001875 compounds Chemical class 0.000 description 58
- 239000008186 active pharmaceutical agent Substances 0.000 description 54
- 229940088679 drug related substance Drugs 0.000 description 54
- 239000000825 pharmaceutical preparation Substances 0.000 description 36
- 229940126534 drug product Drugs 0.000 description 32
- 239000012535 impurity Substances 0.000 description 31
- 229940126601 medicinal product Drugs 0.000 description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- 238000005481 NMR spectroscopy Methods 0.000 description 13
- 239000000523 sample Substances 0.000 description 13
- 239000000243 solution Substances 0.000 description 13
- 208000035475 disorder Diseases 0.000 description 12
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 12
- 238000004458 analytical method Methods 0.000 description 11
- 239000003085 diluting agent Substances 0.000 description 11
- 238000009472 formulation Methods 0.000 description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 238000009826 distribution Methods 0.000 description 8
- 239000012488 sample solution Substances 0.000 description 8
- 150000003839 salts Chemical class 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 230000014759 maintenance of location Effects 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 238000001514 detection method Methods 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 125000004429 atom Chemical group 0.000 description 4
- 239000007853 buffer solution Substances 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 229940127557 pharmaceutical product Drugs 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000012086 standard solution Substances 0.000 description 4
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 3
- 239000005695 Ammonium acetate Substances 0.000 description 3
- 238000001157 Fourier transform infrared spectrum Methods 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 229940043376 ammonium acetate Drugs 0.000 description 3
- 235000019257 ammonium acetate Nutrition 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 239000006194 liquid suspension Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- -1 synergist Substances 0.000 description 3
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 206010067671 Disease complication Diseases 0.000 description 2
- 206010061818 Disease progression Diseases 0.000 description 2
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 102000009659 Vesicular Monoamine Transport Proteins Human genes 0.000 description 2
- 108010020033 Vesicular Monoamine Transport Proteins Proteins 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- SEXRCKWGFSXUOO-UHFFFAOYSA-N benzo[a]phenazine Chemical compound C1=CC=C2N=C3C4=CC=CC=C4C=CC3=NC2=C1 SEXRCKWGFSXUOO-UHFFFAOYSA-N 0.000 description 2
- OCKPCBLVNKHBMX-UHFFFAOYSA-N butylbenzene Chemical class CCCCC1=CC=CC=C1 OCKPCBLVNKHBMX-UHFFFAOYSA-N 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 230000005750 disease progression Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000005570 heteronuclear single quantum coherence Methods 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000003447 ipsilateral effect Effects 0.000 description 2
- 230000007794 irritation Effects 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 231100000062 no-observed-adverse-effect level Toxicity 0.000 description 2
- 239000008024 pharmaceutical diluent Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 238000012430 stability testing Methods 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- MOMFXATYAINJML-UHFFFAOYSA-N 2-Acetylthiazole Chemical group CC(=O)C1=NC=CS1 MOMFXATYAINJML-UHFFFAOYSA-N 0.000 description 1
- BCHZICNRHXRCHY-UHFFFAOYSA-N 2h-oxazine Chemical compound N1OC=CC=C1 BCHZICNRHXRCHY-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 206010001541 Akinesia Diseases 0.000 description 1
- 238000010953 Ames test Methods 0.000 description 1
- 231100000039 Ames test Toxicity 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 208000031404 Chromosome Aberrations Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 208000024453 abnormal involuntary movement Diseases 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 231100000005 chromosome aberration Toxicity 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 238000010954 commercial manufacturing process Methods 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000009266 disease activity Effects 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 238000004049 embossing Methods 0.000 description 1
- 238000003821 enantio-separation Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 231100000024 genotoxic Toxicity 0.000 description 1
- 230000001738 genotoxic effect Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 210000005104 human peripheral blood lymphocyte Anatomy 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000000266 injurious effect Effects 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- UGNWTBMOAKPKBL-UHFFFAOYSA-N tetrachloro-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(Cl)=C(Cl)C1=O UGNWTBMOAKPKBL-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 231100000041 toxicology testing Toxicity 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
Images
Classifications
-
- 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
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/473—Quinolines; Isoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
- Investigating Or Analyzing Non-Biological Materials By The Use Of Chemical Means (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Treatment Of Liquids With Adsorbents In General (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Management, Administration, Business Operations System, And Electronic Commerce (AREA)
- Pens And Brushes (AREA)
- Machine Translation (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762471484P | 2017-03-15 | 2017-03-15 | |
| US62/471,484 | 2017-03-15 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TW201840317A TW201840317A (zh) | 2018-11-16 |
| TWI772382B true TWI772382B (zh) | 2022-08-01 |
Family
ID=61873991
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW107108832A TWI772382B (zh) | 2017-03-15 | 2018-03-15 | 氘代丁苯那嗪(deutetrabenazine)之類似物、其製備方法及用途 |
Country Status (20)
| Country | Link |
|---|---|
| US (4) | US11813232B2 (https=) |
| EP (1) | EP3596077A1 (https=) |
| JP (3) | JP7608050B2 (https=) |
| KR (2) | KR20230003308A (https=) |
| CN (1) | CN110709398A (https=) |
| AR (1) | AR111182A1 (https=) |
| AU (2) | AU2018236336B2 (https=) |
| BR (1) | BR112019018966A2 (https=) |
| CA (1) | CA3056612A1 (https=) |
| CL (1) | CL2019002629A1 (https=) |
| CO (1) | CO2019011271A2 (https=) |
| EA (1) | EA201992168A1 (https=) |
| IL (1) | IL269132A (https=) |
| MX (1) | MX2019010913A (https=) |
| PE (1) | PE20191819A1 (https=) |
| SG (1) | SG11201908477QA (https=) |
| TW (1) | TWI772382B (https=) |
| UA (1) | UA127052C2 (https=) |
| WO (1) | WO2018170214A1 (https=) |
| ZA (1) | ZA201906326B (https=) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| UA127052C2 (uk) | 2017-03-15 | 2023-03-29 | Оспекс Фармасьютікалс, Інк. | Аналоги деутетрабеназину, їхнє отримання та застосування |
| TWI784220B (zh) | 2018-12-13 | 2022-11-21 | 美商奧斯拜客斯製藥有限公司 | 腦性麻痺運動障礙之治療方法 |
| WO2020165807A1 (en) * | 2019-02-14 | 2020-08-20 | Dr. Reddy's Laboratories Limited | Solid forms of deutetrabenazine and process for the preparation thereof |
| US12599598B2 (en) | 2020-06-10 | 2026-04-14 | Auspex Pharmaceuticals Llc | Osmotic dosage forms comprising deutetrabenazine and methods of use thereof |
| US11311488B2 (en) * | 2020-06-10 | 2022-04-26 | Auspex Pharmaceuticals, Inc. | Osmotic dosage forms comprising deutetrabenazine and methods of use thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9233959B2 (en) * | 2012-09-18 | 2016-01-12 | Auspex Pharmaceuticals, Inc. | Formulations and pharmacokinetics of deuterated benzoquinoline inhibitors of vesicular monoamine transporter 2 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL2081929T3 (pl) | 2006-11-08 | 2013-06-28 | Neurocrine Biosciences Inc | Podstawione związki 3-izobutylo-9,10-dimetoksy-1,3,4,6,7,11b-heksahydro-2H-pirydo[2,1-a]izochinolin-2-olowe i ich wytwarzania |
| WO2010044981A2 (en) * | 2008-09-18 | 2010-04-22 | Auspex Pharmaceutical ,Inc. | Benzoquinoline inhibitors of vesicular monoamine transporter 2 |
| CA2801061A1 (en) | 2010-06-01 | 2011-12-08 | Auspex Pharmaceuticals, Inc. | Benzoquinolone inhibitors of vmat2 |
| WO2012081031A1 (en) * | 2010-12-15 | 2012-06-21 | Enaltec Labs Pvt. Ltd. | Process for preparing tetrabenazine |
| US9550780B2 (en) * | 2012-09-18 | 2017-01-24 | Auspex Pharmaceuticals, Inc. | Formulations pharmacokinetics of deuterated benzoquinoline inhibitors of vesicular monoamine transporter 2 |
| EA201791466A1 (ru) * | 2013-12-03 | 2017-11-30 | Оспекс Фармасьютикалз, Инк. | Способы получения соединений бензохинолина |
| HRP20221106T1 (hr) | 2015-03-06 | 2022-11-25 | Auspex Pharmaceuticals, Inc. | Postupci liječenja abnormalnih nevoljnih poremećaja pokreta |
| UA127052C2 (uk) | 2017-03-15 | 2023-03-29 | Оспекс Фармасьютікалс, Інк. | Аналоги деутетрабеназину, їхнє отримання та застосування |
-
2018
- 2018-03-15 UA UAA201910309A patent/UA127052C2/uk unknown
- 2018-03-15 JP JP2019550774A patent/JP7608050B2/ja active Active
- 2018-03-15 PE PE2019001871A patent/PE20191819A1/es unknown
- 2018-03-15 KR KR1020227043234A patent/KR20230003308A/ko not_active Ceased
- 2018-03-15 WO PCT/US2018/022562 patent/WO2018170214A1/en not_active Ceased
- 2018-03-15 SG SG11201908477Q patent/SG11201908477QA/en unknown
- 2018-03-15 AR ARP180100611A patent/AR111182A1/es unknown
- 2018-03-15 KR KR1020197030354A patent/KR20200003791A/ko not_active Ceased
- 2018-03-15 CN CN201880018609.8A patent/CN110709398A/zh active Pending
- 2018-03-15 MX MX2019010913A patent/MX2019010913A/es unknown
- 2018-03-15 EP EP18715393.7A patent/EP3596077A1/en active Pending
- 2018-03-15 BR BR112019018966-1A patent/BR112019018966A2/pt not_active Application Discontinuation
- 2018-03-15 EA EA201992168A patent/EA201992168A1/ru unknown
- 2018-03-15 US US15/922,329 patent/US11813232B2/en active Active
- 2018-03-15 TW TW107108832A patent/TWI772382B/zh active
- 2018-03-15 AU AU2018236336A patent/AU2018236336B2/en active Active
- 2018-03-15 CA CA3056612A patent/CA3056612A1/en active Pending
-
2019
- 2019-09-04 IL IL26913219A patent/IL269132A/en unknown
- 2019-09-13 CL CL2019002629A patent/CL2019002629A1/es unknown
- 2019-09-25 ZA ZA2019/06326A patent/ZA201906326B/en unknown
- 2019-09-25 US US16/582,362 patent/US11179386B2/en active Active
- 2019-10-10 CO CONC2019/0011271A patent/CO2019011271A2/es unknown
-
2021
- 2021-10-21 US US17/507,037 patent/US12502385B2/en active Active
- 2021-11-30 US US17/537,663 patent/US20220088006A1/en not_active Abandoned
-
2022
- 2022-05-18 AU AU2022203369A patent/AU2022203369B2/en active Active
- 2022-11-04 JP JP2022177578A patent/JP2023010754A/ja active Pending
-
2024
- 2024-01-30 JP JP2024011974A patent/JP7631572B2/ja active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9233959B2 (en) * | 2012-09-18 | 2016-01-12 | Auspex Pharmaceuticals, Inc. | Formulations and pharmacokinetics of deuterated benzoquinoline inhibitors of vesicular monoamine transporter 2 |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7631572B2 (ja) | デューテトラベナジンの類似体、その調製及び使用 | |
| EP3872077B1 (en) | Heterocyclic amide for inhibiting rip1 kinase and uses thereof | |
| AU2015237744A1 (en) | Ibrutinib solid forms and production process therefor | |
| CN103930100A (zh) | R(+)-n-甲基-炔丙基-氨基茚满 | |
| JP2014534195A (ja) | ラサギリンシトルアミド | |
| WO2023143455A1 (zh) | 3-[(苯并[d][1,3]二氧戊环-4-基)氧基]丙胺盐酸盐及其光学异构体、晶体及制备方法 | |
| JP2022119840A (ja) | ムスカリン性アセチルコリン受容体アゴニストの結晶性多形 | |
| CN114644642B (zh) | 一种噻吩并吡啶化合物的晶型a、制备方法及其药物组合物 | |
| JP5986635B2 (ja) | ５，６，７，８−テトラヒドロ−６−［ｎ，ｎ−ビス［（２−チエニル）エチル］］アミノ−１−ナフトール、及びその作製方法、及びその使用 | |
| TW202412787A (zh) | 2(1h)-吡啶亞胺衍生物 | |
| EP3985009B1 (en) | B crystal form of tetrahydrothienopyridine compound, preparation method therefor, composition and application | |
| HK40018479A (en) | Analogs of deutetrabenazine, their preparation and use | |
| EA044519B1 (ru) | Способ получения готовой лекарственной формы деутетрабеназина, содержащая его композиция и способ лечения субъекта, страдающего гиперкинетическим двигательным расстройством | |
| CN105585576A (zh) | 银杏内酯k晶l型及制备方法和其组合物与用途 | |
| TW202542164A (zh) | 治療過動性運動障礙之化合物 | |
| CN118359619A (zh) | 一种抗抑郁化合物的盐、其制备方法、包含其的药物组合物及其用途 | |
| HK40072843A (en) | B crystal form of tetrahydrothienopyridine compound, preparation method therefor, composition and application | |
| HK40072843B (en) | B crystal form of tetrahydrothienopyridine compound, preparation method therefor, composition and application |