CA2243243A1

CA2243243A1 - Derives de l'aminotetraline, compositions contenant ces derives et methodes pour les utiliser

Derives de l'aminotetraline, compositions contenant ces derives et methodes pour les utiliser Download PDF

Info

Publication number: CA2243243A1
Authority: CA; Canada
Prior art keywords: methyl; amino; hydrogen; mmol; formula
Prior art date: 1996-03-01
Legal status : Abandoned

Application number

CA 2243243

Other languages

English (en)

Inventor

Edward John Warawa

Bernard Migler

Current Assignee

Syngenta Ltd

Original Assignee

Individual

Priority date

1996-03-01

Filing date

1997-02-25

Publication date

1997-09-04

1997-02-25 Application filed by Individual filed Critical Individual

1997-02-25 Priority claimed from PCT/GB1997/000516 external-priority patent/WO1997031887A1/fr

1997-09-04 Publication of CA2243243A1 publication Critical patent/CA2243243A1/fr

Status Abandoned legal-status Critical Current

Links

238000000034 method Methods 0.000 title claims abstract description 42
JRZGPXSSNPTNMA-UHFFFAOYSA-N 1,2,3,4-tetrahydronaphthalen-1-amine Chemical class C1=CC=C2C(N)CCCC2=C1 JRZGPXSSNPTNMA-UHFFFAOYSA-N 0.000 title abstract description 5
239000000203 mixture Substances 0.000 title description 22
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 37
239000001257 hydrogen Substances 0.000 claims abstract description 37
238000011282 treatment Methods 0.000 claims abstract description 31
150000003839 salts Chemical class 0.000 claims abstract description 29
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 28
229910052736 halogen Inorganic materials 0.000 claims abstract description 24
150000002367 halogens Chemical group 0.000 claims abstract description 24
208000016285 Movement disease Diseases 0.000 claims abstract description 15
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 12
230000002265 prevention Effects 0.000 claims abstract description 9
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 4
150000002431 hydrogen Chemical group 0.000 claims abstract 14
150000001875 compounds Chemical class 0.000 claims description 109
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 37
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 23
-1 bromo, methoxy, ethoxy Chemical group 0.000 claims description 22
239000003638 chemical reducing agent Substances 0.000 claims description 12
229910052740 iodine Inorganic materials 0.000 claims description 11
239000003814 drug Substances 0.000 claims description 9
PMZSOOOPRABQMS-FVGYRXGTSA-N (2s)-5,8-dimethoxy-n-methyl-1,2,3,4-tetrahydronaphthalen-2-amine;hydrochloride Chemical compound Cl.COC1=CC=C(OC)C2=C1C[C@@H](NC)CC2 PMZSOOOPRABQMS-FVGYRXGTSA-N 0.000 claims description 6
WWRJRKPCRXJACI-JTQLQIEISA-N (2s)-8-methoxy-n-methyl-1,2,3,4-tetrahydronaphthalen-2-amine Chemical compound C1=CC(OC)=C2C[C@@H](NC)CCC2=C1 WWRJRKPCRXJACI-JTQLQIEISA-N 0.000 claims description 6
206010043118 Tardive Dyskinesia Diseases 0.000 claims description 6
ZSIAKNKANPQFTH-PPHPATTJSA-N (2s)-8-methoxy-n-methyl-1,2,3,4-tetrahydronaphthalen-2-amine;hydrochloride Chemical compound Cl.C1=CC(OC)=C2C[C@@H](NC)CCC2=C1 ZSIAKNKANPQFTH-PPHPATTJSA-N 0.000 claims description 5
239000002671 adjuvant Substances 0.000 claims description 5
239000003981 vehicle Substances 0.000 claims description 5
239000003085 diluting agent Substances 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims description 4
PMZSOOOPRABQMS-UHFFFAOYSA-N 5,8-dimethoxy-n-methyl-1,2,3,4-tetrahydronaphthalen-2-amine;hydrochloride Chemical compound Cl.COC1=CC=C(OC)C2=C1CC(NC)CC2 PMZSOOOPRABQMS-UHFFFAOYSA-N 0.000 claims description 3
BJFHJWRQUZEHRE-UHFFFAOYSA-N 6-bromo-5,8-dimethoxy-n-methyl-1,2,3,4-tetrahydronaphthalen-2-amine;hydrochloride Chemical compound Cl.COC1=CC(Br)=C(OC)C2=C1CC(NC)CC2 BJFHJWRQUZEHRE-UHFFFAOYSA-N 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
CKXFPBHAUKEBBF-UHFFFAOYSA-N n-ethyl-5,8-dimethoxy-1,2,3,4-tetrahydronaphthalen-2-amine;hydrochloride Chemical compound Cl.C1=CC(OC)=C2CC(NCC)CCC2=C1OC CKXFPBHAUKEBBF-UHFFFAOYSA-N 0.000 claims description 3
CKXFPBHAUKEBBF-PPHPATTJSA-N (2s)-n-ethyl-5,8-dimethoxy-1,2,3,4-tetrahydronaphthalen-2-amine;hydrochloride Chemical compound Cl.C1=CC(OC)=C2C[C@@H](NCC)CCC2=C1OC CKXFPBHAUKEBBF-PPHPATTJSA-N 0.000 claims description 2
AAFPRLDUYSCCGD-UHFFFAOYSA-N 5-bromo-8-methoxy-n-methyl-1,2,3,4-tetrahydronaphthalen-2-amine;hydrochloride Chemical compound Cl.C1=CC(OC)=C2CC(NC)CCC2=C1Br AAFPRLDUYSCCGD-UHFFFAOYSA-N 0.000 claims description 2
LYMDZJCFPOOCBO-UHFFFAOYSA-N 5-ethoxy-8-methoxy-n-methyl-1,2,3,4-tetrahydronaphthalen-2-amine;hydrochloride Chemical compound Cl.C1C(NC)CCC2=C1C(OC)=CC=C2OCC LYMDZJCFPOOCBO-UHFFFAOYSA-N 0.000 claims description 2
ZSIAKNKANPQFTH-UHFFFAOYSA-N 8-methoxy-n-methyl-1,2,3,4-tetrahydronaphthalen-2-amine;hydrochloride Chemical compound Cl.C1=CC(OC)=C2CC(NC)CCC2=C1 ZSIAKNKANPQFTH-UHFFFAOYSA-N 0.000 claims description 2
125000000066 S-methyl group Chemical group [H]C([H])([H])S* 0.000 claims 2
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 147
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 121
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 105
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 71
239000000243 solution Substances 0.000 description 69
239000002904 solvent Substances 0.000 description 57
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 50
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 48
239000000741 silica gel Substances 0.000 description 45
229910002027 silica gel Inorganic materials 0.000 description 45
229960001866 silicon dioxide Drugs 0.000 description 45
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 43
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 42
239000007787 solid Substances 0.000 description 40
229910001868 water Inorganic materials 0.000 description 39
238000001914 filtration Methods 0.000 description 33
239000000463 material Substances 0.000 description 31
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 27
239000003921 oil Substances 0.000 description 26
235000019198 oils Nutrition 0.000 description 26
UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 24
239000012267 brine Substances 0.000 description 24
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 24
LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 22
238000010992 reflux Methods 0.000 description 22
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
208000012661 Dyskinesia Diseases 0.000 description 20
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 20
238000012360 testing method Methods 0.000 description 19
241000282693 Cercopithecidae Species 0.000 description 18
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
230000002829 reductive effect Effects 0.000 description 18
239000003176 neuroleptic agent Substances 0.000 description 17
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 16
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 16
241000282668 Cebus Species 0.000 description 15
238000006243 chemical reaction Methods 0.000 description 15
238000001035 drying Methods 0.000 description 14
229910052943 magnesium sulfate Inorganic materials 0.000 description 14
230000000142 dyskinetic effect Effects 0.000 description 13
239000003960 organic solvent Substances 0.000 description 13
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
229910000085 borane Inorganic materials 0.000 description 12
239000012230 colorless oil Substances 0.000 description 12
230000017311 musculoskeletal movement, spinal reflex action Effects 0.000 description 12
239000002244 precipitate Substances 0.000 description 12
238000003756 stirring Methods 0.000 description 12
KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 11
238000004458 analytical method Methods 0.000 description 11
238000009835 boiling Methods 0.000 description 11
229960003878 haloperidol Drugs 0.000 description 11
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 10
238000000023 Kugelrohr distillation Methods 0.000 description 10
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
239000002024 ethyl acetate extract Substances 0.000 description 10
239000011630 iodine Substances 0.000 description 10
235000019341 magnesium sulphate Nutrition 0.000 description 10
208000015592 Involuntary movements Diseases 0.000 description 9
150000001412 amines Chemical class 0.000 description 9
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 9
238000004809 thin layer chromatography Methods 0.000 description 9
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 8
241000699670 Mus sp. Species 0.000 description 8
239000002585 base Substances 0.000 description 8
235000019253 formic acid Nutrition 0.000 description 8
239000012279 sodium borohydride Substances 0.000 description 8
229910000033 sodium borohydride Inorganic materials 0.000 description 8
239000007858 starting material Substances 0.000 description 8
239000002253 acid Substances 0.000 description 7
239000013058 crude material Substances 0.000 description 7
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 7
239000011734 sodium Substances 0.000 description 7
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
LCGFVWKNXLRFIF-UHFFFAOYSA-N 1,2,3,4-tetrahydronaphthalen-2-amine Chemical class C1=CC=C2CC(N)CCC2=C1 LCGFVWKNXLRFIF-UHFFFAOYSA-N 0.000 description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
208000035475 disorder Diseases 0.000 description 6
229940079593 drug Drugs 0.000 description 6
208000010118 dystonia Diseases 0.000 description 6
239000012458 free base Substances 0.000 description 6
238000004128 high performance liquid chromatography Methods 0.000 description 6
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
238000002360 preparation method Methods 0.000 description 6
239000000047 product Substances 0.000 description 6
238000000746 purification Methods 0.000 description 6
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
206010008748 Chorea Diseases 0.000 description 5
241000699666 Mus <mouse, genus> Species 0.000 description 5
HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 5
239000003377 acid catalyst Substances 0.000 description 5
229960004046 apomorphine Drugs 0.000 description 5
238000004440 column chromatography Methods 0.000 description 5
238000001816 cooling Methods 0.000 description 5
239000012259 ether extract Substances 0.000 description 5
238000003810 ethyl acetate extraction Methods 0.000 description 5
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 5
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 5
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 5
239000010410 layer Substances 0.000 description 5
KKKDGYXNGYJJRX-UHFFFAOYSA-M silver nitrite Chemical compound [Ag+].[O-]N=O KKKDGYXNGYJJRX-UHFFFAOYSA-M 0.000 description 5
229910000029 sodium carbonate Inorganic materials 0.000 description 5
241000894007 species Species 0.000 description 5
239000000725 suspension Substances 0.000 description 5
125000004055 thiomethyl group Chemical group [H]SC([H])([H])* 0.000 description 5
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
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 4
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
208000009017 Athetosis Diseases 0.000 description 4
208000014094 Dystonic disease Diseases 0.000 description 4
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
208000002033 Myoclonus Diseases 0.000 description 4
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
230000001476 alcoholic effect Effects 0.000 description 4
VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 4
OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 4
125000004432 carbon atom Chemical group C* 0.000 description 4
230000003197 catalytic effect Effects 0.000 description 4
208000012601 choreatic disease Diseases 0.000 description 4
238000004587 chromatography analysis Methods 0.000 description 4
238000001514 detection method Methods 0.000 description 4
VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 4
230000000694 effects Effects 0.000 description 4
238000010438 heat treatment Methods 0.000 description 4
239000003701 inert diluent Substances 0.000 description 4
239000007788 liquid Substances 0.000 description 4
238000003760 magnetic stirring Methods 0.000 description 4
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
230000000701 neuroleptic effect Effects 0.000 description 4
229910052757 nitrogen Inorganic materials 0.000 description 4
KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 4
239000011541 reaction mixture Substances 0.000 description 4
229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 4
235000017550 sodium carbonate Nutrition 0.000 description 4
230000009182 swimming Effects 0.000 description 4
208000011580 syndromic disease Diseases 0.000 description 4
238000003786 synthesis reaction Methods 0.000 description 4
239000006188 syrup Substances 0.000 description 4
235000020357 syrup Nutrition 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
RSYYSWWHZPCDIT-UHFFFAOYSA-N 5,8-dimethoxy-1,4-dihydronaphthalene Chemical compound C1C=CCC2=C1C(OC)=CC=C2OC RSYYSWWHZPCDIT-UHFFFAOYSA-N 0.000 description 3
208000023105 Huntington disease Diseases 0.000 description 3
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
208000027089 Parkinsonian disease Diseases 0.000 description 3
206010034010 Parkinsonism Diseases 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
206010044074 Torticollis Diseases 0.000 description 3
150000001298 alcohols Chemical class 0.000 description 3
229910052783 alkali metal Inorganic materials 0.000 description 3
235000019270 ammonium chloride Nutrition 0.000 description 3
229940035678 anti-parkinson drug Drugs 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
239000002775 capsule Substances 0.000 description 3
229910052799 carbon Inorganic materials 0.000 description 3
230000009194 climbing Effects 0.000 description 3
WQOXQRCZOLPYPM-UHFFFAOYSA-N dimethyl disulfide Chemical compound CSSC WQOXQRCZOLPYPM-UHFFFAOYSA-N 0.000 description 3
239000000284 extract Substances 0.000 description 3
201000002886 generalized dystonia Diseases 0.000 description 3
125000005843 halogen group Chemical group 0.000 description 3
208000018197 inherited torticollis Diseases 0.000 description 3
150000002500 ions Chemical class 0.000 description 3
235000019359 magnesium stearate Nutrition 0.000 description 3
238000002844 melting Methods 0.000 description 3
230000008018 melting Effects 0.000 description 3
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 3
GIDPMYYHJSLJSK-JTQLQIEISA-N n-[(2s)-8-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl]formamide Chemical compound C1C[C@H](NC=O)CC2=C1C=CC=C2OC GIDPMYYHJSLJSK-JTQLQIEISA-N 0.000 description 3
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 3
229920000053 polysorbate 80 Polymers 0.000 description 3
230000003252 repetitive effect Effects 0.000 description 3
229910052708 sodium Inorganic materials 0.000 description 3
239000000126 substance Substances 0.000 description 3
238000010998 test method Methods 0.000 description 3
RVKOHSCTEHZRRT-VIFPVBQESA-N (2s)-8-methoxy-1,2,3,4-tetrahydronaphthalen-2-amine Chemical compound C1C[C@H](N)CC2=C1C=CC=C2OC RVKOHSCTEHZRRT-VIFPVBQESA-N 0.000 description 2
JTYYNNSRXWOIEE-UHFFFAOYSA-N (3-bromo-2,5-dimethoxyphenyl)methanol Chemical compound COC1=CC(Br)=C(OC)C(CO)=C1 JTYYNNSRXWOIEE-UHFFFAOYSA-N 0.000 description 2
MURVUTUZSUEIGI-UHFFFAOYSA-N 1-bromo-2-(bromomethyl)-4-methoxybenzene Chemical compound COC1=CC=C(Br)C(CBr)=C1 MURVUTUZSUEIGI-UHFFFAOYSA-N 0.000 description 2
WMDHQEHPOVOEOG-UHFFFAOYSA-N 2-(2-bromoethyl)-1,3-dioxane Chemical compound BrCCC1OCCCO1 WMDHQEHPOVOEOG-UHFFFAOYSA-N 0.000 description 2
ZJYJZEAJZXVAMF-UHFFFAOYSA-N 2-nitronaphthalene Chemical compound C1=CC=CC2=CC([N+](=O)[O-])=CC=C21 ZJYJZEAJZXVAMF-UHFFFAOYSA-N 0.000 description 2
BENQALZXOPIFJI-UHFFFAOYSA-N 5-ethoxy-8-methoxy-1,2,3,4-tetrahydronaphthalen-2-amine Chemical compound C1C(N)CCC2=C1C(OC)=CC=C2OCC BENQALZXOPIFJI-UHFFFAOYSA-N 0.000 description 2
XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 2
XRVNUXUNETXLEU-UHFFFAOYSA-N 7-bromo-5,8-dimethoxy-1,2-dihydronaphthalene Chemical compound C1CC=CC2=C1C(OC)=C(Br)C=C2OC XRVNUXUNETXLEU-UHFFFAOYSA-N 0.000 description 2
JAPSPAAIOIOFEZ-UHFFFAOYSA-N 8-bromo-5-methoxy-1,2-dihydronaphthalene Chemical compound C1CC=CC2=C1C(Br)=CC=C2OC JAPSPAAIOIOFEZ-UHFFFAOYSA-N 0.000 description 2
UFKBXCDTAVOEDJ-UHFFFAOYSA-N 8-ethoxy-5-methoxy-1,2-dihydronaphthalene Chemical compound C1=CCCC2=C1C(OC)=CC=C2OCC UFKBXCDTAVOEDJ-UHFFFAOYSA-N 0.000 description 2
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